Module 5

Pharmaceutics

Drug Delivery System, Manufacturing, Physical Pharmacy,

Jurisprudence

Kathreen Mae D. Cascabel

BSPharmacy
Drug Delivery System
DRUG
o Article intended for the use in diagnosis, mitigation, cure, treatment, or prevention of disease in man/animals
o Article (other than food) intended to affect the structure of any function of the body of human beings or animals
o Component which produces pharmacologic activity (Active Pharmaceutical Ingredient)
o Therapeutic moiety

EXCIPIENTS
o Inactive ingredient present in DF

DOSAGE FORM
o Formulation containing a specific quantity of AI(s) in combination with one or more excipients

DRUG PRODUCT/MEDICINE
o Final dosage form that contains the API, generally, but not necessarily, in association with other ingredients

DRUG DELIVERY SYSTEMS

o Physical carriers used to deliver medications to specific areas
o Means of administering drugs to the body in a safe, efficient, reproducible and convenient manner

USP Requirements
1. Natural products should be free from Salmonella spp.
2. Oral Solutions and suspensions should be free from E. coli.
3. Topical products must be free from Pseudomonas aeruginosa
4. Urethral, vaginal and rectal should be free from total microbial count
o
Manufacturing
The complete set of activities to produce a drug that comprise production and QC from dispensing of materials to the
release for distribution of the finished product (AO 43 s 1999)

Drug Establishment
o any organization or company involved in the manuf, import, packaging and/or distribution of drugs or
medicines (AO 56 s 1989)

Manufacturer Production of drug AO 56 s 1989 and IRR of RA 9711

Trader Registered owner, subcontracts the manufacturer, may AO 56 s 1989 and IRR of RA 9711
also engage in distribution and marketing
Distributor/ Imports/exports for own use or wholesale distribution IRR of RA 9711
Importer/Exporter to other establishments
Distributor/ Procures from a local establishment for local IRR of RA 9711
Wholesaler distribution on wholesale basis

Intermediate Product

more stages of production

Bulk Product

packaging

Finished Product

Good Manufacturing Practice (GMP)

o Part of QA which ensures that products are consistently produced and controlled to the quality standards
appropriate to their intended use (WHO, 2007)
o System of QA aimed at ensuring that products are consistently manufactured to a quality appropriate for their
intended use and is concerned with both manuf and QC processes and procedures (AO 43 s 1999)
o Examples: US FDA, WHO, EU, ASEAN, PIC/S
o PIC/S GMP 2009 (Pharmaceutical Inspection Convention/Co-operation Scheme)
PACKAGING (Primary or Secondary)

CONTAINER – holds the drug product and is or may be in direct contact with the drug product
Well-closed - protects from extraneous solids and loss of article
Tight - protects from contamination by extraneous liquid, solids, vapors, loss,
efflorescence, deliquesence, or evaporation
Hermetic - impervious to air or any other gas
Single-dose - holds a quantity intended for single dose; cannot be resealed
Multiple-dose - permits withdrawal of successive portions
Single-unit - holds a quantity of a drug intended for admin as a single dose promptly after opening
Multiple-unit - contains more than a single unit or dose
Light-resistant
Child-resistant - not for under 5 years old
Tamper-evident - uses an indication or barrier to entry distinctive by design
Compliance packaging

PACKAGING MATERIALS
1. Glass – available in white flint (clear), amber, or colored
I – borosilicate
II – treated SL (exempted form water attack test)
III – soda lime
NP – gen. SL

2. Plastic
 Polyethylene, Polyvinyl chloride, Polypropylene, Polystyrene
 Problems: Permeability, Leaching, Sorption, Light transmission, Alteration upon storage

3. Metal – tin, aluminum, aluminum alloy

4. Paper and Board – labels, cartons, layer boards
5. Films, foils and laminations – sachets, seals, strips, blisters
6. Rubber – closure for sterile products

STORAGE CONDITIONS
TERM CONDITION
Cold Not exceeding 8°C
Freezer -25 to -10°C
Refrigerator 2 to 8 °C
Cool 8 to 15°C
Controlled Room Temperature 2 to 8°C but allows excursions between 0 to 15°C
Room Temperature 20 to 25°C (prevailing in working area)
Warm 30 to 40°C
Excessive Heat Above 40°C
Dry Place Does not exceed 40% of average RH at Controlled RT
 Monograph Document that specifies all the tests to be conducted on a product and/or appropriate
references containing details of procedure and expected result

Certificate of Document with the results of all tests conducted on material to show compliance or non-
Analysis compliance with the standard specifications

Formula This is concise and precise statement of the ingredients that comprise the product,
together with the percentage and/or weight of each.

Raw material This should enumerate the characteristics of all the materials that go into the product and
specification the permissible range of purity of each ingredient.

Standard Operating This is a step by step method on how to go about a job.

Procedure
Finished product This should cover all characteristics that affect the proper performance, purity, safety and
specification stability of the product.

Sample Finite number of objects selected from a batch

STABILITY
o Capacity of drug to remain within specifications
o Minimum Acceptable Potency Level: 90% Labeled Potency

OVERAGE – excess medicaments in manufacturing unstable drugs

A 15% decrease in potency of antibiotics is considered admissible for unstable antibiotics, but the ff overages
normally should not exceed:
1. 15% - dry DFs
2. 20% - fluids
3. 25% - ointment, suppositories, aerosols, creams, and foams
 SOLID DOSAGE FORMS
POWDERS
o Intimate mixtures of dry, finely divided drugs and or chemicals (internal or external use)
o Adv: flexibility in compounding | D/A: easily wetted by liquids, inaccuracy of dose, not for hygroscopic

Comminution of Drugs
• Trituration or Comminution – mortar and pestle (small scale)
• Milling – cutter mill, roller mill, hammer mill (large scale)
• Levigation – form a smooth paste (L agent: mineral oil, glycerine, propylene glycol)
• Pulverization with Intervention – addition of a volatile solvent (camphor + OH, iodine crystals + ether)

Particle Size
Very Coarse (no. 8)
Coarse (no. 20)
Substances that form eutectic mixtures:
Moderately Coarse (no. 40)
Camphor
Fine (no. 60) Menthol
Very Fine (no. 80) Thymol
Aspirin
Blending Powders Phenyl salicylate
• Trituration
Inert diluents to prevent eutexia:
• Spatulation Light magnesium oxide
• Sifting/Lifting Magnesium carbonate
• Tumbling
• Geometric dilution – for potent substances

Types of Powders:
Medicated Powders – intended to be used internally or externally
Aerosol Powders – administered by inhalation with the aid of dry-powder inhalers
Bulk Powders – medicated preparations provided to the patient in bulk (non-potent medicaments)
1. Oral – also antibiotic syrups reconstituted before use
2. Dentifrices – cleansing and polishing the teeth; may contain fluoride
3. Douches – intended for the cavity
4. Dusting Powders – formulated in sifter-top
5. Insufflations – medicated powders designed to be blown into the ear, nose, throat or
body cavities by means of a device known as an insufflator
6. Triturations – the finely powdered, medicinal substance is ground for a certain time in
a mortar and pestle with a certain proportion of sugar and milk

Divided Powders – “chartula” each dose is separately wrapped in paper or sealed in a sachet (for potent)
1. White bond – no moisture-resistant properties
2. Vegetable parchment – limited moisture resistant qualities
3. Glassine – moisture-resistant paper
4. Waxed – waterproof
CAPSULE
o SDF in which medicinal agents and or inert substances are enclosed in a small shell of gelatin
o Gelatin is prepared by the enzymatic hydrolysis of collagen, which is the main protein constituent of connective
tissues in animal bones and skin
Gelatin A (acid hydrolysis of porcine skin)
Gelatin B (base hydrolysis of bovine bones)
o Bloom strength – measure of gelatin rigidity (HGC: 200-250g; SGC: 150g)

Hard Gelatin Capsules (Dry Filled Capsules)

 used in extemporaneous compounding Capsule Size Capacity (mL)
 shell made from gelatin + sugar + water 000 (veterinary) 1.40
 parts: capsule body and cap 00 0.95
0 0.68
 + 0.15% sulfur dioxide to prevent decomposition during manufacture
1 0.50
 12-15/13-16% moisture
2 0.37
3 0.30
Processes:
4 0.21
1. Punch Method 5 0.13
2. Hand-operated Filling Machine

Soft Gelatin Capsules

 made of gelatin + glycerin or polyhydric alcohol (sorbitol) for elasticity and plasticity
 5-8/6-10% moisture
 Used for:
 Water-immiscible volatile and non-volatile liquids
 Water-miscible non-volatile liquids
 Water-miscible and relatively non-volatile compounds

Processes:
1. Plate process (Upjohn Co.)
2. Rotary die process (Robert P. Scherer, 1933)
3. Reciprocating die process – Norton Capsule Machine; vertical; continually open and close
4. Accogel Capsule Machine ( Lederle Laboratories, 1948) – can fill dry powder into softgels
TABLET - mixture of active substances and excipients, usually in powder form, compacted into a solid

COMPRESSED TABLETS (made by Wet granulation, Dry granulation, Direct compression)

Sugar Coated (SCT) - sugar fpr palatability; adds 50% to tablet bulk
Chewable Tablets - broken and chewed before ingestion; mannitol (50% of tablet bulk); xylitol (sugar free)
Film Coated (FCT) - coated with a thin layer of a polymer capable of forming a skinlike film; less bulky
Enteric Coated (ECT) - disintegrate in intestinal fluid; delayed release
Multiple Compressed (MCT) - compressing the fill material more than once
a. Layered (multiple layered)
b. Press-coated/Dry coated (tablet within a tablet)
Controlled Release (CR) - aka prolonged release or sustained release; releases the med over a period of time
Tablets for Solution - ex. Halazone tablets and KMnO4 tablets for solution
Effervescent Tablets - compressed granular effervescent salts; Na bicarbonate + citric acid + tartaric acid
Buccal Tablets - dissolved at the buccal/cheeks of the mouth
Sublingual Tablets - dissolved under the tongue

Immediate Release - designed to release their medication with no rate controlling features
Modified Release - have drug release features based on time, course, and/or location
Extended Release - aka Controlled Release; release medication over an extended period
Delayed Release - release at a time other than promptly after administration
Repeat Action - 2 single doses, one for immediate, another for delayed
Targeted Release - directed towards a region, tissue, or site of absorption

MOLDED TABLETS/TABLET TRITURATE (small, usually cylindrical tablet w/ small amounts of potent drugs)
Dispensing Tablets (DT) - aka Compounding Tablets; for extemporaneous compounding, never dispensed as DF
Hypodermic Tablets (HT) - no longer used because of the difficulty in achieving sterility
Vaginal Tablets - aka Vaginal inserts; bullet or ovoid shaped inserted for local or systemic effects

OTHER SOLID DOSAGE FORMS FOR ORAL ADMINISTRATION

Contains one or more medicinal agents in a flavoured, sweetened base intended to dissolve
Lozenges
slowly in the mouth

Lollipops Sugar based lozenges on a stick and contain fentanyl citrate

Troches Compressed lozenges; discoid shaped

Molded lozenges
Pastilles
Softer and has a higher concentration of sugar or gelatin

Inserts SDF other than suppositories for insertion to body orifices

Small, sterile SDF containing a concentrated drug for SC implantation where it continuously
Implants/Pellets
release the medication over long periods
EXCIPIENTS
ESSENTIAL COMPONENTS
Diluent/Bulking Agent Advantages Disadvantages
Lactose  Inexpensive  Lubricants required
 Readily soluble  Binders may have to be added when
Coarse granular (60-80)  High MP (202°C) other substances interfere with
Regular (100) cohesion
Spray-dried (100-120) Advantages of spray-dried:
 Flows readily (spherical granules)
 Flow maintained even when wet
granulated
 No need for binders
 For direct compression method
Starches  Also used as binders and disintegrants
 Provide moisture balance even though
moisture content is 12-14%
 Stabilize hygroscopic drugs (protect
them from deterioration)
Mannitol  For water-sensitive drugs  Expensive
 For chewable (sweet, negative heat of
solution – cooling sensation)
Sorbitol  For direct tableting  Very hygroscopic above 65% RH
Sucrose  Provide additional sweetness  Somewhat hygroscopic (should only be
 Serves as binder (cohesive) in small ratio)
 Contributes to dissolution (readily  Turns brown with acidic or basic subst
soluble)
Microcrystalline Cellulose  For direct compression  Needs lubricant (when drug is present)
(Avicel)  At 5-15% conc in wet granulations:  Expensive
a. Minimizes tablet hardening
b. Reduces mottling

Binders/Granulators – provide mechanical strength

Starch Paste 10-20% w/w
Aqueous gelatin solution 10-20% w/w
Aqueous glucose solution 25-50% w/w
Alcoholic solution of ethylcellulose 5% w/w
Others Acacia, Alginic acid, Compressible sugar (Nu-Tab), Povidone

Disintegrants
Starches Corn and Potato
Clays Bentonite and Veegum
Cellulose Methylcellulose, Sodium Carboxymethylcellulose, Microcrystalline cellulose (Avicel)
Algins Alginic acid and sodium alginate
Gums Locust bean, karaya, guar, tragacanth, agar
Effervescent mixtures Disintegrates rapidly
 COMPRESSION AIDS

Glidants Enables to flow from hopper Silicon dioxide (Cabosil)/Colloidal silica

Cornstarch
Talc
Lubricants Prevent adhesion to dies and punches Talc
Reduce friction Stearates
Release tablet from die Mineral oil
May improve flow Stearic acid
Antiadhesives Prevent residue films on punches Magnesium stearate
Talc

SUPPLEMETARY COMPONENTS

Colors FD&C # Name

Lakes (Al(OH)3; insoluble in water) Blue #1 Brilliant Blue
Blue #2 Indigotine
Pastel shades - colorants of choice (least likely to show mottling)
Green #3 Fast Green
Red #2 Amaranth
Approaches to add colorants: Red #3 Erythrosine
1. Incorporate soluble dye (0.3% max) before granulation Red #40 Allura Red
2. Adsorb the dye on starch or Ca sulfate Yellow #5 Tatrazine
3. Blended dry with portion of diluent  dry mixing Yellow #6 Sunset Yellow

Flavors Sweet Honey, fruits, berries, maple, vanilla

Oils and spray dried beadlets Bitter Chocolate, anise, cherry mint, nut, fennel
Never added during wet processing (volatile) Sour Citrus, rootbeer, anise, cherry, strawberry, licorice
Salty Butterscotch, maple, peach, melon, raspberry
Metallic Grape, lemon, lime
Alkaline Chocolate, cream, vanilla, mint

Sweetening agents Diluents Sucrose, Lactose, Dextrose

Saccharin 250-500x, bitter aftertaste
Aspartame 200x
Mannitol 70%
Xylitol sugar free
Na cyclamate
Sucrose Disadvantage: cap-locking (syrups/LDFs)

Adsorbents
Silicon dioxide Can hold up to 50% of its weight in water
Others Mg carbonate/ hydroxide, Bentonite, Kaolin, Mg Al silicate, Tricalcium phosphate, dried starch
Parts of Tablet Press
1. Hopper - stores materials for compressing
2. Feed frame - distributes materials into dies
3. Dies - controls the size and shape of the tablet
4. Punches - compacts materials within the dies (also controls shape)
5. Cams - guide the punches

Types of Tablet Press

1. Single-punch press/eccentric press – about 200 tabs per min
2. Rotary press/multi station press – over 10,000 tabs per min

Tablet Manuf: Powder mixing  Granulation  Die filling  Powder/granule compression  Tablet ejection

Common Tablet Processing Problems

1. Chipping - separation of small piece of tablet surface after ejection
2. Capping - partial or complete separation of top and bottom from the main body
3. Lamination - 2 or more distinct layers
4. Picking - removal from tablet surface and adherence to the face of the punch
5. Sticking - adhesion to die wall
6. Mottling - unequal color distribution
7. Bridging - stick to the sides of the hopper
8. Weight variation
9. Hardness variation
10. Double impression

GRANULES
o moistening the desired powder and passing the moistened mass thru screen in the 4 to 12 mesh sieve;
o consists of powder particles that have been aggregated to form a larger particle (0.2-4mm)
o Must possess: Fluidity and Compressibility

Effervescent Granulated Salts (sodium bicarbonate, citric acid, and tartaric acid)
 Citric acid only – sticky | Tartaric acid only – crumble
 Prepared by: Fusion method or wet method

Wet granulation (widely used) Dry granulation/Fusion/Force Compression

1. Wet massing 1. Roller compaction/Roll press
2. Fluidized bed 2. Slugging (“slug” is a large crude tablet,
25mm in diameter by 10-15mm thick)
Mill  Weigh  Mix  Granulate  Screen Weigh  Mix  Slug  Screen 
 Dry  Dry screen  Lubricate  Compress Disintegrant/Lubricant  Compress

Other granulation processes:

1. Spheronization - uses Marumerizer machine (Elanco)
2. Spray-drying - bring together highly dispersed liquid and hot air  evaporation & drying
3. Spray-congealing - aka spray chilling; no heat applied
TABLET COATING
Pan coating - sugar and film; coating pans provided with hot and cold air
Air suspension coating - film; coating material is atomized and applied to tablets as they are suspended (chamber)
Dip coating - placed in baskets and dipped into containers of coating solutions
Compression coating - for two incompatible drugs

1. Sugar Coating
a. Sealing /Waterproofing (shellac, cellulose acetate phthalate, polyvinyl acetate phthalate, zein)
b. Subcoating (gelatin, acacia gum, Ca carbonate, talc)
c. Syruping/Smoothing/Color – cover and fill imperfections
 Grossing
 Heav syruping
 Regular sruping
d. Finishing
e. Polishing (beeswax, carnauba wax)
f. Imprinting

2. Film Coating (Pan pour, Pan spray, Fluidized bed) – involves the deposition of a thin film of polymer
Film former Produce smooth, thin films Cellulose Acetate Phthalate
Alloying substance Provide water solubility/permeability Polyethylene glycol
Plasticizer Flexibility and elasticity Castor oil, Propylene glycol, PEGs
Surfactant Enhance spreadability of the film Polyoxyethylene sorbitan derivatives
Opaquants, Colorants Aesthetic Titanium dioxide, FD&C, D&C
Sweeteners, Flavors Patient acceptability Saccharin, Vanillin
Glossant Luster Beeswax
Volatile solvent Spread of other components over the tab Alcohol + Acetone

Film coating problems:

 Picking - small flaking
 Peeling - large flaking
 Orange-peel effect - roughness of surface due to failure of spray droplets to coalesce
 Mottling - uneven color distribution
 Bridging - filling in of score lie or logo
 Tablet erosion - disfiguration of the core when subjected in the coating for too long

3. Microencapsulation – modified form of film-coating differing only in particle size

4. Press/Compression coating – compact of granular material around an already preformed tablet core
5. Electrostatic coating – to apply films in conductive materials
6. Laminated coating – provide a second action or layer of medicament
7. Enteric Coating – Shellac, Hydroxypropyl methylcellulose phthalate, polyvinyl acetate
phthalate, diethyl phthalate, cellulose acetate phthalate
 SEMI-SOLID DOSAGE FORMS
OINTMENTS - Semisolid preparations for external application to the skin or mucous membrane
Preparation:
1. Incorporation – trituration in a mortar or an ointment slab
2. Fusion – melted together and cooled until congealed

Ointment Bases Description Examples

Emollient
Petrolatum/Petroleum jelly
Protect against escape of moisture
White petrolatum
Oleaginous/Hydrocarbon Occlusive dressings
Yellow/Simple ointment
Remain on skin w/o drying
White ointment
Difficult to wash off

Permit incorporation of aqueous solutions Lanolin (0.25% water)

resulting in w/o emulsion (Anhydrous) Hydrophilic petrolatum
Absorption (anhydrous)
Permit incorporation of additional quantities of Anhydrous lanolin (25-30%)
aqueous solutions (w/o emulsions) Cold cream

O/W emulsions resembling creams

Hydrophilic ointment
Water-removable/Washable Easily washed
Vanishing cream
Can absorb serous discharges
No oleaginous components
Completely water-washable
Water-soluble/Greaseless Soften greatly with water PEG (Carbowax)
Large amounts of water is NOT added
For incorporation of solid substances

CREAMS
o Semisolid preparations containing one or more medical agents dissolved or dispersed in either a W/O emulsion or
another type of water washable base (O/W)
o O/W Type: Shaving creams, hand creams and foundation creams
o W/O Type: Cold creams (+ Na borate as antifungal preservative) and Emollient creams
o Vanishing creams: o/w containing large percentage of water and stearic acid

GELS
o Dispersions of small or large molecules in an aqueous liquid vehicle rendered jellylike by adding a gelling agent
Synthetic macromolecules - Carbomer 934
Cellulose derivatives - Carboxymethylcellulose, hydroxypropylmethylcellulose
Natural gums - tragacanth
o Singe Phase Gels macromolecules are uniformly distributed throughout a liquid
o Two-phase Systems/Magma if particles of dispersed phase are relatively large; has small distinct particles
DRESSING – resemble ointments, for burns; remain semisolid at body temperature, liquefy at 50°C
PASTES – for skin application, thicker, stiffer, less greasy, more absorptive of serous secretions than ointments

PLASTERS – semisolid or solid adhesive masses spread on a backing of paper, fabric, moleskin, or plastic adhesive
GLYCEROGELATINS – long-term, applied with a fine brush
gelatin (15%)
glycerin (40%)
water (35%)
medicinal substance (10%)

TERMS:
Imbibition – taking up liquid without measurable increase in volume
Syneresis – gel sinks, loss of liquid
Swelling – taking up liquid with increase in volume
Thixotropy – reversible gel-sol formation with no volume or temperature changes
Xerogel – liquid is removed, framework remains

TRANSDERMAL PREPARATIONS
o With penetration enhancers Example Transdermal Preparations
– Dimethyl sulfoxide (DMSO)
– Ethanol Scopolamine - motion sickness
– Oleic acid Nitroglycerin - angina
– Acetone Clonidine - hypertension
– Azone Nicotine - smoking cessation adjunct
– Propylene glycol Estradiol - menopausal symptoms
– Urea Testosterone
– Dimethyl acetamide Contraceptives
– SLS
– Poloxamers (SPANS, TWEENS, Lecithin, Terpenes)
o Advantages:
– Avoid GI absorption difficulties
– Substitute for oral
– Avoid first pass effect
– Noninvasive
– Extended therapy with single application
– Extends half-life of drugs
– Can be terminated rapidly
– Easily identified in emergencies
o Disadvantages:
– Only for potent drugs
– Contact dermatitis
 SUPPOSITORIES AND INSERTS

SUPPOSITORIES – intended for insertion to body orifices

Stiffening agents: Cetyl alcohol, Cetyl ester wax, Microcrystalline wax, Paraffin, Stearyl alcohol, White/Yellow wax
Sodium stearate – solidifier for glycerine suppositories
Synonym Weight Length Shape Example
Vaginal Pessaries 5g 70 mm Globular, oviform, cone Glycerinated gelatin
Urethral Bougies 4g 140 mm Pencil PEG
Rectal 2g 32 mm Cylindrical with ends tapered Cocoa butter
Bullet/torpedo

Suppository Bases
1. Fatty/Oleaginous Bases
• Cocoa butter – exhibits polymorphism (melts at 30 to 36°C)
Phenol and Chloral hydrate (lowers MP of cocoa butter)
Remedy: Cetyl ester wax (20%) or Beeswax (4%) – solidifiers
• Wecobee oil – coconut oil
• Witepsol oil – fatty acid (c12-c18)
• Hydrogenated FAs of vegetable oils (Palm kernel oil and cottonseed oil)
• Glyceryl monopalmitate, glyceryl monostearate

2. Water-soluble and Water-miscible Bases

• Glycerinated gelatins – gelatin (20%) glycerin (70%) medication (10%); vaginal, hygroscopic
• Polyethylene glycols – does not melt at body temp; dissolve in body fluids

3. Miscellaneous Base
• mixtures of oleaginous and water-miscible bases
• Polyoxyl 40 stearate (MP: 39 to 45°C)

Preparation:
1. Hang molding
2. Cold Compression
3. Fusion/Melt molding/Pour molding

Packaging
1. Tightly closed glass containers
2. Compartmented boxes
3. Opaque material (metallic foil)
4. Continuous strip
5. Slide boxes
6. Plastic boxes
 LIQUID DOSAGE FORMS
Solutions - liquid preparation which contains one or more substances dissolved in a suitable solvent

Solubility – maximum concentration to which a solution can be formed Methods of Preparing Solutions
Very soluble <1  Simple Solution
Freely soluble 1-10  Application of Heat
Soluble 10-30  Addition of a Co-Solvent
Sparingly soluble 30-100  Rigorous Agitation
Slightly soluble 100-1,000  Solution by Extraction
Very slightly soluble 1,000-10,000 o Liver solution
Practically insoluble >10,000  Solution by Chemical reaction
o MgCO3 + Citric Acid
 Mg Citrate + CO2
WATER
o most commonly used solvent
o USP recognizes 7 types of water for DF preparation

Purified water Obtained by distillation, ion-exchange, reverse osmosis, etc.

ph 5-7 Preparation of aqueous dosage forms EXCEPT parenterals

Purified water FREE of pyrogens

WFI Obtained by distillation or reverse osmosis
For parenterals that are to be sterilized after preparation

WFI sterilized and packaged into single-dose containers < 1 Liter

SWFI
Used for already sterilized and packaged medication

SWFI that contains antimicrobial agent

BWFI
Single or multi-dose containers < 30 mL

Distillation or reverse osmosis and rendered sterile inhalation

SWF Inhalation
Not for parenterals

WFI sterilized and suitably packaged

SWF Irrigation “For irrigation use only, Not for injection”
 Agua Oxinada
 Burrow’s Solution (Aluminum Acetate Solution)

PW sterilized and suitably packaged

Sterile Purified Water
Not for parenterals
AQUEOUS SOLUTIONS (clear liquid prescriptions, and homogeneous in nature)

Used both as a vehicle and as a solvent for the desired flavoring or medicinal
Waters
ingredients

Aromatic Waters A clear saturated aqueous solution (unless otherwise specified) of volatile oils or other
(medicated aromatic or volatile substances
waters)
Preparation of Aromatic Waters:
Flavored vehicle for
water soluble drugs
1. Distillation/Cohobation (Stronger Rose Water NF)
2. Solution Method
Aqueous phase in (Dissolve 2mg/mL v.o in 1L water; stay overnight and filter off excess oil)
some emulsions or 3. Alternate Solution Method
suspensions
(Triturate 2mg/2mL v.o with talc clarifying agent; dissolve in 1L water and filter)

Aqueous Acids
Prepared by diluting the corresponding concentrated acids with purified water
(diluted acids)

Solutions Homogeneous mixture composed of two or more substances

Douches Directed against a part or into a body cavity for cleansing and antiseptic action (using
bulb syringe)

 Evacuation enemas (Fleet Enema)

Enemas
 Absorption/Retention enemas (Aminophylline)
 Affect locally the site of disease (Hydrocortisone Enema)

Aqueous solutions frequently containing antiseptics, antibiotics and/or anesthetics

Gargles used for treating the pharynx and nasopharynx by forcing air from the lungs through
the gargles which is held in the throat (Golden Gargle: Fe + K + CO3 -2, Bactidol)

Mostly aqueous solution with some alcohol or glycerine present usually pleasantly
Mouthwashes flavored and often colored; employed for deodorant, refreshing or antiseptic effect
Local anti-infective - hexetidine and cetylpyridine chloride

Prepared from fresh ripe fruit, is aqueous in character and is used in making syrups
Juices
which are employed as vehicles (preservative: Benzoic acid)
NON-AQUEOUS SOLUTIONS

Alcoholic and Hydroalcoholic solutions

Elixirs  Clear, pleasantly flavored, sweetened hydroalcoholic liquids for oral use
(5-40% OH)  Contain alcohol and are thus incompatible with acacia, tragacanth and inorganic salts from
aqueous solutions as precipitation may occur
 Aromatic  Less sweet and less viscous than syrup
Elixir 22%  10-20% alcohol – self-preserving
Preparation of Elixirs:
1 Simple solution with agitation
2 Admixture of 2 or more liquid ingredients
Spirits  Alcoholic or hydroalcoholic solutions of volatile substances
/Essences  When mixed with water or other aqueous preparation, the volatile substances in spirits
(over 60%) generally separate from solution and form milky preparation
Preparation of Spirits
1 Simple Solution w/Agitation – Aromatic Spirit of Ammonia
2 Solution with Maceration – Peppermint Spirit
3 Chemical Reactions – Ethyl Nitrite Spirit/Amyl nitrite Spirit
4 Distillation
Brandy (Spiritus Vini Vitis) – distillation of fermented juice or ripe grapes
Whisky (Spiritus Frumenti) – fermented malted grain

Ethereal Solutions
Colloidons Liquid preparations containing pyroxylin in a mixture of 3 parts ether and 1 part alcohol
Pyroxylin (soluble gun cotton, nitrocellulose, collodion cotton) is obtained by the action of a
mixture of nitric and sulfuric acids on cotton

Flexible Colloidon – 2% camphor (water proof)

3% castor oil (flexibility)
Salicylic Acid Colloidon – flexible colloidon + 10% SA

Glycerine Solutions
Glycerites Solutions or mixtures of medicinal substances in nlt 50% by weight of glycerine; hygroscopic

Oleaginous Solutions
Liniments Intended to be rubbed on the skin (Embrocation)

Oleovitamins Fish-liver oils diluted with edible vegetable oil or solutions of the indicated vitamins (A and D)
Oleates Formed by reacting alkaloids, basic oxides or hydroxides with oleic acid
Toothache
Temporary relief of toothache by a small pledget of cotton (Clove oil, which contains eugenol)
Drops
Medicated Solutions for Vaporization
Inhalations Administered by the nasal route or oral respiratory route for either a local or systemic effect
Carried into the respiratory passage by the use of special delivery systems (ex. Aerosols)
Inhalants Carried by an air current into the nasal passage by virtue of the drug’s high vapour pressure

Topical Solutions
Sprays Aqueous or oleaginous solutions in the form of coarse droplets or finely divided powders
(usually to the nasopharyngeal tract or through the skin)
Astringents Constrict pores and precipitate proteins
 Aluminum acetate, Aluminum subacetate , Calcuim hydroxide topical solution
Local Anti- These kill microorganisms when applied to the skin or the mucous membranes
infectives  Povidone iodine, Thimerosal , Hydrogen peroxide topical solution

Extractives
 These are preparations obtained from plants and animals with the aid of a solvent
 Separation of medicinally active portions from inactive components

Methods of Extraction
1. Maceration Solid + solvent in stoppered container; allowed to stand for a period of time
2. Digestion Maceration with gentle heating
3. Percolation Maceration which involves the use of a percolator
4. Decoction Boiling in water for 15 minutes
5. Infusion Maceration in hot or cold water
Extracts Concentrated preparations of vegetable or animal drugs obtained by removal of active
constituents with suitable menstrua (6x as potent as crude drug); usually by percolation

3 forms of extracts
1. Semi-liquid Syrupy consistency
2. Pillular/Solid Plastic consistency; for ointments and suppositories
3. Powder For manufacture of tablets and capsules

Fluid Extracts Liquid preparation of vegetable drugs containing alcohol as solvent (100% tincture)
(1ml/1g drug)
Preparation of Fluid Extracts
A: Sets first 85% of the percolate & collect the weak percolate until exhaustion
C: Commercial
D: Boiling water (menstruum), alcohol (preservative)
E: Alternative for A; conducted in a longer column

Tinctures Alcoholic or hydroalcoholic solutions prepared from vegetable materials or from chemical subs
(15% to 80%)
Preparation
1. Process P (percolation) Belladona tincture
2. Process M (maceration) Sweet orange peel tincture
3. Simple solution Iodine tincture
SWEET OR VISCID SOLUTIONS
Syrups Concentrated aqueous preparations of a sugar or sugar substitute with or without added
60-80% flavoring agents and medicinal substances
Simple Syrup – concentrated solution of sucrose in purified water
Medicated Syrup – syrup containing a therapeutic or medicinal agent
Flavored Syrup – intended to serve as pleasant tasting vehicle or flavorant for medicines

Preparation of Syrups
1 Solution with the aid of heat
2 Solution by agitation
3 Reconstitution – addition of sucrose to a prepared medicated or flavored liquid
4 Percolation – passage of a solvent thru a bed of sucrose at 1mL/ min (Ipecac syrup)

Syrup/Simple syrup
- nearly saturated solution of sucrose (85% w/v or 65% w/v with a sp.gr. of 1.3)
- No need for preservative if it is to be used soon
- Sucrose substitutes: Sorbitol, Glycerine, Propylene glycol
- Nonglycogenetics: Methylcellulose, hydroxyl ethylcellulose
- Add 5 to 10% ethanol to prevent bacterial growth in surface dilution

Honeys Thick liquid preparations somewhat allied to the syrups, differing in that honey, instead of
syrup, is used as a base (invert sugar, chief constituent of honey)

Example: Squill Oxymel (oxymel mixture of honey and acetic acid)

Mucilages These are thick, viscid adhesive liquids prepared by:

 Dispersion of gums in water
 Extraction of mucilages and its principles from vegetable materials

Prone to decomposition (decrease in viscosity on storage) and they should never be made in
larger quantities than can be used immediately, unless preservative (benzoic acid) is added

Jellies Class of gels in which the structural coherent matrix contains a high portion of liquid (water)

Formulation
1. Solvent (aqueous & nonaqueous)
2. Co-solvent (ethanol, sorbitol, glycerine, propylene glycol)
3. Buffer (carbonates, citrates, gluconates, lactates, phosphates, tartrates, acetates)
4. Solubilizer (surfactants, cyclodextrins, complexing agents)
5. Density modifier (dextrose)
6. Isotonicity modifier (NaCl, dextrose, boric acid)
7. Viscosity enhancer (sucrose, PVP, HEC, carbomer)
8. Antifungal Preservative (parabens, benzoic acid, Na benzoate, Na propionate)
9. Antimicrobial Preserv. (benzalkonium Cl, Cetylpyridinum Cl, Chlorobutanol, Phenol, Thimerosal)
10. Antioxidant (Na meta/bisulphite, BHA, BHT, ascorbic acid, Na formaldehyde sulfoxylate)
11. Sweetener (sucrose, sorbitol, mannitol, xylitol, glycerine, aspartame, acesulfame K)
12. Coloring (natural, synthetic)
13. Flavoring (natural, artificial)
 Sweet Honey, fruits, berries, maple, vanilla
Bitter Chocolate, anise, cherry mint, nut, fennel
Sour Citrus, rootbeer, anise, cherry, strawberry, licorice
Salty Butterscotch, maple, peach, melon, raspberry
Metallic Grape, lemon, lime

Clarification – removal/separation of a solid from a liquid, or a fluid from another fluid (by filtration or centrifugation)
Types of Filtration
1. Solid/fluid
2. Solid/gas
3. Fluid/fluid

Types of Filtration Equipment

1. Gravity filters
2. Vacuum filters
3. Pressure filters

Types of Industrial Centrifuge

1. Perforated - basket centrifuges/centrifugal filters (for separation of crystalline materials)
2. Tubular - bowl centrifuges/centrifugal sedimenters (for liquid-liquid separation)

Filter media
1. Filter cloth (woven)
 Stainless wire
 Cotton
 Nylon (unaffected by microbes, can be autoclaved)
2. Nonwoven
 Felt (for gelatinous solutions – ex. Asbestos pad)
 Kraft paper (bonded fabric)
3. Membrane filter
4. Filter aids
 Diatomite (diatomaceous earth, infusorial earth, celite, super cel)
 Perlite
 Cellulose
 Asbestos
 Carbon
Thrombus – within vessel
Emboli – carried by blood
STERILE PREPARATIONS
o Subject to special requirements in order to minimize the risks of microbe contamination, and of particulate and
pyrogen contamination

Parenterals - injection through one or more layers of skin or mucous membranes

Intravenous - vein; butterfly
Sterile Intra-articular - joint
Pyrogen-Free Intraspinal - spinal column Sites of IM injection:
Isotonic Intrathecal - spinal fluid
Adults: Upper Quadrant of Gluteus maximus
Intracardiac - heart Infants: Deltoid, Midlateral muscles of the thigh
Intramuscular - muscle
Intradermal/Intracutaneous
Subcutaneous/Hypodermic
Nasal Solutions - Administered to the nasal passages in drops or sprays
Otic - For instillation into the ear
Ophthalmic - For instillation into the eye
Irrigating Solutions - Wash or bathe surgical inclusions, wounds or body tissues “Not for injection, For Irrigation only”

VEHICLES
1. Water (specifically Water for Injection)
– Most frequently employed vehicle
– Total solids content: 10ppm
– Electrolytic measurement of conductivity: nmt 1 micromho (1 megohm, approx. 0.1 ppm NaCl)

2. Nonaqueous Solvents
– Polyethylene glycol, Propylene glycol, Fixed oils

PYROGENS
o Lipid substances associated with a carrier molecule, usually a polysaccharide but may be a protein
o Product of microbial metabolism (produces febrile reactions about an hour after injection)

Official tests:
1. Bacterial Endotoxin Test
 Uses Limulus Amebocyte Lysate (LAL) from the horseshoe crab, Limulus polyphemus
 Quantities defined in Endotoxin Units (EU)

3. Pyrogen Test
 Done in rabbits
 Nmt 10ml/kg IV within a period of nmt 10 minutes
 Pass if: no rabbit shows individual rise in temp 0.6°C or above, sum does not exceed 1.4°C

Depyrogenation Method:
1. Adequate washing with detergent + dry heat sterilization for glasswares and equipment
2. Distillation for water
3. Adsorbents for antibiotics
ADDITIVES
Phenylmercuric nitrate
Thimerosal
p-hydroxybenzoic acid
Antibacterial/Antifungal For multiple-dose containers
phenol
Benzyl alcohol
Chlorobutanol
Ascorbic acid
Na meta/bisulfite
Na formaldehyde sulfoxylate
Reducing Agents
Thiourea
Hydrogen peroxide
Oxalic acid
Ascorbic acid esters
Blocking agents (blocks oxidation) Butylhydroxytoluene
Tocopherols
Ascorbic acid
Antioxidants Citric acid
Synergists (increases antoxidant effect) Citraconic acid
Phosphoric acid
Tartaric acid

Chelating agets Ethylenediaminetetraacetic acid salts

Nitrogen
Inert gases (displace oxygen)
Carbon dioxide

Acetates
Buffers Maintain required pH Citrates
Phosphates

Tonicity Contributors Isotonicity to reduce pain on injection site NaCl

CONTAINERS
Glass – Silicon dioxide tetrahedron; manufactured from glass tubings or by molding; Rubber closures to seal
I – borosilicate
II – treated SL (exempted form water attack test)
III – soda lime
NP – gen. SL
PRODUCTION Bubble test
1. Compounding - Measures efficiency
2. Filtration - membrane filter (3 microns); sterilization by filtration (0.3 microns) of membrane filters
3. Filling
4. Sealing - Ampuls – high temperature gas-oxygen flame (Tip/bead seal and Pull seal)
Leaker’s test (0.5 to 1% methylene blue) – not for vials and bottles
5. Sterilization
Sterilization Equipment Biologic Indicators Temp Time
Steam Autoclave B. stearothermophilus 121°C
Dry Heat Oven B. subtilis 150-170°C Nlt 2 hours
Ionizing Radiation Gamma and cathode rays Both + B. pumilus
UV light 2537 Å
Millipor Membrane filter
Gas Ethylene oxide B. stearothermophilus 50-60°C 4-16 hours
Beta propiolactone
Formaldehyde
Sulfur dioxide
Ethylene dioxide (plastics)
Tyndallization/ 100°C 30 mins
Intermittent Sterilization 80°C 1 hour
For 3 days
Surface disinfection

Clean Area
- An area, room, or zone, with defined environmental control of particulate and microbial contamination,
constructed and used in such a way as to reduce the introduction, generation and retention of contaminants
within the area

Airlock
- Enclosed space with two or more doors, which is interposed between two or more rooms, for the purpose of
controlling the airflow between those rooms when they need to be entered

Clean areas are classified according to the required characteristics of the environment:
 Grade A
- High risk operations (filling, stopper bowls, open ampoules and vials, aseptic connections)
- Provided with laminar air flow work station with a HEPA filter (0.45m/s)
 Most drugs: Horizontal airflow, positive pressure facility
 Chemotherapeutic drugs: Vertical airflow, negative pressure facility
 Curvilinear
Grade B
- For aseptic preparation and filling
- The background environment for grade A zone

Grades C & D
- Clean areas for carrying out less critical stages in the manufacture of sterile products

The description for clothing required for each grade:

Grades A & B
- Headgear should totally enclose hair and, where relevant, beard and mustache; it should be tucked into the
neck of the suit
- A face mask should be worn to prevent shedding of droplets
- Appropriate sterilized, non-powdered rubber or plastic gloves and sterilized or disinfected footwear should be
worn
- Trouser-legs should be tucked inside the footwear and garment sleeves into the gloves
- Protective clothing should shed virtually no fibers or particulate matter and retain particles shed by the body

Grade C
- Hair and where relevant beard and mustache should be covered
- A single or two-piece trouser suit, gathered at the wrists and with high neck and appropriate shoes or
overshoes should be worn; should shed virtually no fibers or particulate matte

Grade D
- Hair and where relevant beard and mustache should be covered
- A general overprotective suit and appropriate shoes or overshoes should be worn
- Appropriate measures should be taken to avoid any contamination from outside the clean area

US FED STD 209E cleanroom standards

3
maximum particles/ft ISO
Class
≥0.1 µm ≥0.2 µm ≥0.3 µm ≥0.5 µm ≥5 µm equivalent
1 35 7.5 3 1 0.007 ISO 3
10 350 75 30 10 0.07 ISO 4
100 3,500 750 300 100 0.7 ISO 5
1,000 35,000 7,500 3000 1,000 7 ISO 6
10,000 350,000 75,000 30,000 10,000 70 ISO 7
6
100,000 3.5×10 750,000 300,000 100,000 700 ISO 8
 DISPERSE SYSTEMS
Coarse Dispersions 10-50 μm Suspensions and Emulsions
Fine dispersions 0.5-10 μm Gels and Magmas
Colloidal dispersions 1 nm – 5μm

SUSPENSION (>0.5 mcm) – Two-phase system consisting of finely divided solid dispersed in a solid, liquid or gas
Properties:
- Settle slowly, easily dispersed with gentle shaking. Problem: Caking
- Particle size should remain fairly constant in long periods of undisturbed standing
- Pour slowly and evenly in the container

Particle Size Reduction:

1. Micropulverization
2. Fluid energy grinding/Jet milling/ Jet micronizing
3. Spray-drying

Preparation:
1. Comminute
2. Wetting agent – Levigation to displace air in the crevices of the particle to make drug penetrable
(surfactants with HLB 7-9, hydrophilic colloids, alcohol, glycerine, glycols)
3. Suspending agent dispersed in the vehicle is added to the melted powder by geometric dilution
Polysaccharides Acacia, tragacanth, alginic acid, xanthan
Cellulose derivatives Methyl-, hydroxyethyl-, Na carboxymethyl- (carmellose Na), Avicel
Hydrated silicates Bentonite, Veegum (Mg Al silicate), hectorite
Misc Carbomer, colloidal silicon dioxide, PVP
4. The product is brought to final volume using the vehicle
5. Homogenize (homogenizer, colloid mill)

Gels Semisolid system consisting of either suspension made up of small inorg particles or large
inorg molecules interpenetrated by liquid
Gelling agents: mostly less than 10%
Single Phase Gels No apparent boundaries exist between the macromolecules and the liquid
Milks & Magmas (Two-phase) Differ from gels mainly in that the suspended particles are larger
Lotions Liquid or semiliquid preparations which contain one or more active ingredients in a vehicle
Jellies Class of gels in which the structural coherent matrix contains a high proportion of liquid
Mixtures Aqueous liquids containing suspended insoluble material intended for internal use
(Kaopectate, Bordeaux mixture- CuSO4)

Instability of Gels
a. Syneresis - shrinking, some liquid is pressed out
b. Bleeding - liberation of oil or water due to deficient gel structure
c. Swelling - taking up of liquid with volume increase
d. Imbibition - taking up of liquid without volume increase
EMULSION (down to 0.1-100 mcm but optimum is between 0.5 to 2.5 mcm)
o Two-phase system prepared by combining two immiscible liquids, one of which is dispersed uniformly throughout
the other
3 phases:
o dispersed phase/internal phase/continuous phase (O/W)
o dispersion medium/external phase/discontinuous phase (W/O)
o emulsifying agent – for stability

Synthetic and Semisynthetic Surfactants

Anionic Soaps, Sodium Lauryl Sulfate
Cationic Quaternary ammonium compounds, cetrimide
Non-ionic Sorbitan esters (Spans), polysorbates (Tweens)
Amphteric Lecithin
Naturally-occurring
Polysaccharides Acacia, tragacanth, methylcellulose, carmellose sodium
Sterol-containing Beeswax, anhydrous lanolin
Finely-divided solids Bentonite (Al silicate), veegum (MgAl silicate), colloidal silicon dioxide

Theories of Emulsification
1. Surface Tension Theory - surfactant lowers surface tension
2. Oriented-Wedge Theory - monomolecular layers of emulsifying agent curved around a droplet of IP
3. Plastic/Interfacial Film Theory - emulsifying agent at the interface between the oil and water

Types of Emulsions:
4. O/W
5. W/O
6. Multiple emulsions – O/W/O or W/O/W
7. Microemulsions – appear transparent or translucent and have droplet diameter in the nm size range,
thermodynamically and optically stable

Methods of Preparation: (mortar and pestle, mechanical blender, hand homogenizer, mixing tanks)
1 Dry gum/Continental/4:2:1 – 4 oil + 1 emulsifier + 2 water rapidly (4:1:2)
2 Wet gum/English – 2 water + 1 emulsifier + 4 oil slowly (2:1:4)
3 Forbes Bottle Method – extemporaneous compounding of emulsion from volatile oils
4 Nascent soap/In Situ Method – alkali OH + FA (Calcium soap and soft soap)

Problems:
Creaming – upward movement, reversible
HLB SYSTEM
Cracking/Breaking – complete separation, irreversible
Sedimentation – downward movement, reversible Antifoaming 1-3
W/O 3-6
Wetting 7-9
O/W 8-18
Solubilizers 15-20
Detergents 13-16
COLLOIDAL DISPERSIONS/SOL (1 nm – 5μm)
AEROSOL
o Colloidal systems consisting of very finely subdivided liquid or solid dispered in and surrounded by a gas
o Products which depend upon the power of a liquefied or compressed gas to dispense the active ingredient(s) in a
finely dispersed mist, foam or semisolid
o MDI’s: < 10 micrometers, usually 3-6 micrometers for maximum therapeutic response
o Explodes when exposed to temp >49°C. Ideal: 15-30°C

Types of Aerosols
1. Space Sprays <50 micrometers
2. Surface sprays 50-200 micrometers
3. Foams

Components:
1. Product Concentrate
2. Propellant
Chlorofluorocarbon (CFC) Trichloromonofluoromethane, Dichlorodifluoromethane,
Dichlorotetrafluoroethane
Hydrochlorofluorocarbons (HCFC) Chlorodifluoromethane, Trifluoromonofluoroethane,
and Hydrofluorocarbons (HFC) Chlorodifluoroethane, Difluoroethane, Heptafluoropropane
Hydrocarbons Propane, Isobutane, Butane
Compressed Gases nitrogen, nitrous oxide, and carbon dioxide

Valves
1. Conventional/Continuous spray valve
2. Metered valve

Valve Assembly – regulates the flow of product concentrate from the container
Actuator Release contents by pressing down
Stem Supports the actuator, delivers the formulation to the chamber of the actuator
Gasket Prevent leakage when valve is still closed
Spring Holds the gasket in place, allows retraction of actuator when pressure is released thereby returning
the valve to the closed position
Mounting Cup Holds the valve in place (aka ferrule)
Housing Below the mounting cup; link between the dip tube and the stem and actuator
Dip Tube Extends from the housing down into the product concentrate, brings the formulation from the
container to the valve

Containers
1. Tin-plated steel - most widely used; light weight, relatively inexpensive
2. Aluminum - more resistant to corrosion (subject to corrosion by water and ethanol – needs coating)
3. Stainless steel - very resistant to corrosion (no coating required); withstand high pressures; expensive
4. Glass containers - often coated with plastic to resist impact; transparent
5. Plastic containers - not extensively used (polyethyleneterephthalate/PET is used for non-pharmaceuticals)

Two methods are used to manufacture aerosols: the cold fill process (-34.5 to -40°C) and the pressure fill process
 COSMETICS
o External application to the human body for cleansing, beautifying, promoting attractiveness, altering appearance

CREAMS AND LOTIONS

Cosmetic Cream – soft viscous liquid or semisolid emulsion of the O/W or W/O type
Lotion – fluid or thixotropic emulsion or suspension

1. Cleansing creams and lotions (Beeswax-borax emulsion/Cold cream) To prepare C&L:

2. Emollient creams and lotions – to prevent dryness 1. Prepare oil phase
3. Hand creams and lotions – to moisturize 2. Prepare water phase
4. Suntan creams and lotions (sunblock) 3. Add water to oil
5. Skin lightener 4. Milling
5. Fill and Pack
6. Shaving creams

FACE POWDERS
o Has the ability to complement skin color by imparting a velvet like finish

ROUGE
o Any cosmetic product used to tint the face a shade of red (iron oxides are used)

LIPSTICKS
o Composed essentially of an oil-wax base still stiff enough to form a stick, with a red staining dye dissolved or
dispersed in oil, red pigments suspended therein, suitably perfumed and flavoured
o Color grinding  Mixing  Molding  Flaming

EYE MAKE-UP
1. Eyeshadow - cream, stick, liquid, poweder or pressed cake
2. Mascara - cake, cream, or liquid, applied with a “wand”; with added fibers for lengthening
3. Eyebrow makeup - crayon, extruded pencil, stick, cream, or pressed cake
4. Eyeliner - liquid, cream or pressed cake applied with a brush or pencil
5. False eyelashes
6. Cover-makeup/Concealer
7. Makeup remover
8. Eye cream or eyestick

DENTRIFICES
o Intended for use with toothbrush for the purpose of cleaning surfaces of the teeth
o Fluoride compounds are added for effective control of dental caries or tooth decay

DEPILATORIES
o Epilation – removing intact hair by uprooting (wax rosin or adhesive semisolid)
o Depilation – result of chemical degradation of the human fiber
SHAMPOO
o Preparation of surfactant in a suitable form which when used under the conditions specified will remove surface
grease, dirt, skin debris from the hair shaft and scalp
o With sequestering agents like EDTA to hinder formation of insoluble Ca or Mg soap curd

ANTIPERSPIRANT AND DEODORANTS

o Deodorants – mask, remove, or decrease perspiration odors
o Antiperspirants – reduce perspiration without stopping it
o Aluminum sulfate reduces total bacterial count in the axilla of over 95%
o Aluminum chlorhydrate (20%) is most widely used

NAIL LACQUER OR ENAMEL

o Must contain a film former (Nitrocellulose)

FRAGRANCE/PERUME
o Concentrated alcoholic blend of fragrant materials
o Perfume oil is the base used to impart fragrance (best incorporated at the earliest period of manufacture)

Fragrance Type Description

Oriental A blend of fragrant complexes culminating in an intense heavy full-bodied fragrance
Cologne blend Any harmonious combination whose fragrance are derived from citrus oils
Bouquet Harmonious combination of two or more floral notes
Floral Fragrance of an existing known flower type
Chypre Mossy-woody complex with a characteristic sweet citrus top note
Fougre Combines a dominant sweet note with a mossy, lavender, citrus character
Spice blend Either floral spice (carnation) or herbal spice
Wood blend Dominated by woody notes
Amber Heavy full bodied powdery, warm scent tone

Definition Examples
Top Notes Most volatile products Lemon oil, Lavender oil, Anise oil
Leave the skin readily
Middle Notes Intermediate tenacity Thyme oil, Neroli oil, Rose oil
and volatility
Base Notes Low volatility and high Musk
aka Fixatives tenacity  Dried secretion from the preputial follicles of
the male musk deer of Asia (Moschus spp)
Civet
 A glandular secretion appearing in an outwardly
discharging pockets of Civet cats (Paradoxurus
hermaphroditus)
Ambergris
 Most valuable material
 Pathologic product formed in the stomach of
spermwhale when it feeds on squid or cattlefish
Physical Pharmacy
 Application of physical and chemical principles and laws in the pharmaceutical sciences
 To understand and develop dosage forms and drug delivery systems
 FORCES OF ATTRACTION
Atom – basic unit of matter | proton, neutron, electron

INTRAMOLECULAR FORCES – within molecules

1. Ionic Bond - transfer
2. Covalent Bond - sharing
a. Polar (unequal)
b. Nonpolar (equal)

INTERMOLECULAR FORCES – between molecules; physical attraction

1. Van der Waals
a. Keesom (Dipole-dipole)
o Orientation/Alignment effect
o 1-7 kcal/mole

b. Debye (Dipole-Induced Dipole)

o Induction
o 1-3 kcal/mole

c. London Dispersion (Induced dipole-Induced dipole)

o Very close proximity  internal vibration will cause dispersion of charges
o 0.5-1 kcal/mole

2. Ion-Dipole - polar molecules are attracted to positive or negative charges (salt & water)
3. Ion-Induced Dipole - induced by the close proximity of a charged ion to a nonpolar molecule (I2 + KI)
4. Hydrogen Bond - between H and electronegative atom (F, O, N, Cl, S) ; can be intramolecular (A=T)

Physical Properties of Systems

1. Additive Property - depends on sum | molecular weight
2. Constitutive Property - type and arrangement | optical rotation, refractive index
3. Colligative Property - number of components | VPL, BPE, FPD, OP

Types of Properties
1. Extensive/Extrinsic - dependent on size/amount | length, volume
2. Intensive/Intrinsic - independent | specific gravity, viscosity

Density = mass per unit volume (M/V)

Specific gravity = density of sample/density of standard
1. Pycnometer method
2. Mohr Westphal Balance
3. Plummet method (Archimedes principle: buoyancy – wt of immersed is equal to displaced)
Specific volume = reciprocal of specific gravity, opposite of density
 STATES OF MATTER

PLASMA (Mesophase/Liquid Crystal)

1. Smectic - soap like, mobile in two directions
2. Nematic - thread like, mobile in three directions
3. Cholesteric - special case of nematic type

Methods of forming liquid crystals:

1. Lyotropic (using solvent)
2. Thermotropic (using heat)

SUPERCRITICAL FLUID STATE (Between liquid and gas)

GASES
o Have kinetic energy that produces rapid motion
o Held together by weak intermolecular forces
o Capable of filling all available spaces (Compressible)

Kinetic Theory of Gases:

1. Distances are much greater than the sizes of the molecules. Volume is negligible.
2. Do not attract one another but rather move independently from each other
3. Molecules are in constant, random motion.
4. Collisions are perfectly elastic.
5. Average kinetic energy is directly proportional to the absolute temperature.

10
Gas molecules are in rapid and continuous motion at ordinary temp & pressure (0.1-1 km/sec | 10 collisions/sec)

IDEAL GAS NON-IDEAL (REAL) GAS

Point mass (so small, nearly zero) Point mass but attracts
No volume Has volume
Collisions are “elastic” (not sticky, no attractive and repulsive Has attractive and repulsive forces
force)
Kinetic energy remains constant Kinetic energy decreases
Moves in random motion Moves in random slow motion until forms solid
Does not condense Condenses and sublimes
Follows ideal gas equation: PV = nRT Van der Waals equation: (P + an2/V2) (V – nb) =nRT
 GAS LAW FORMULA CONSTANT

𝟏
Boyle's/Mariotte 𝑷₁𝑽₁ = 𝑷₂𝑽₂ 𝑜𝑟 𝑷 ∝𝑽 Temperature

𝑽₁ 𝑽₂
Charles' = 𝑜𝑟 𝑽∝𝑻 Pressure
𝑻₁ 𝑻₂

𝑷₁ 𝑷₂
Gay-Lussac's = 𝑜𝑟 𝑷∝𝑻 Volume
𝑻₁ 𝑻₂

𝑷₁𝑽₁ 𝑷₂𝑽₂
Combined =
𝑻₁ 𝑻₂
𝐿.𝑎𝑡𝑚
R = 0.08206
𝑚𝑜𝑙.𝐾
At STP:
Ideal 𝑷𝑽 = 𝒏𝑹𝑻 T = 273.15 K
P = 1 atm
V = 22.4 L
𝒂𝒏𝟐
(𝑷 + ) (𝑽 − 𝒏𝒃) = 𝒏𝑹𝑻
𝒗𝟐
Real/Van der Waals
an2 = internal pressure per mole
nb = incompressibility
𝑷𝒔𝒐𝒍𝒖𝒕𝒊𝒐𝒏 = 𝑿𝒔𝒐𝒍𝒗𝒆𝒏𝒕 𝑷𝒔𝒐𝒍𝒗𝒆𝒏𝒕
Rauolt’s Temperature
X = mole fraction

Henry’s Law of Gas

𝑷𝒓𝒆𝒔𝒔𝒖𝒓𝒆 ∝ 𝑺𝒐𝒍𝒖𝒃𝒊𝒍𝒊𝒕𝒚 Temperature
Solubility
Total pressure in a mixture is equal to the sum of
Dalton’s Law of Partial
the partial pressures of each gas
Pressures
𝑃𝑡 = 𝑃1 + 𝑃2 + 𝑃3 … ….
Volume of gas at STP is directly proportional to the
Avogadro’s number of moles k = 6.022 X 1023
𝑽₁ 𝑽₂ 𝑽
= 𝑜𝑟 𝑽 ∝ 𝒏 𝑜𝑟 =𝒌
𝒏₁ 𝒏₂ 𝒏
Rate of diffusion and speed gas are inversely
proportional to the square root of their density
Graham’s
1
𝑅𝑎𝑡𝑒𝑑𝑖𝑓𝑓𝑢𝑠𝑖𝑜𝑛 ∝
√𝑑𝑒𝑛𝑠𝑖𝑡𝑦
LIQUIDS
o Possess less kinetic energy than gases
o Occupy a definite volume
o Take the shape of the container
o Incompressible

Vapour Pressure – pressure of the saturated vapour above a liquid resulting from the escape of surface liquid molecules

Clausius – Clapeyron Equation – relation of vapour pressure and absolute temp of liquid

𝑷𝟐 ∆𝑯𝒗 (𝑻𝟐 − 𝑻𝟏 )
𝒍𝒐𝒈 =
𝑷𝟏 𝟐. 𝟑𝟎𝟑 𝑹𝑻𝟏 𝑻𝟐

∆𝐻𝑣 = molar heat of vaporization

𝐜𝐚𝐥 𝑱
R = molar gas constant (𝟏. 𝟗𝟖𝟕 𝐦𝐨𝐥.𝐊 𝐨𝐫 𝐨𝐫 𝟖. 𝟑𝟏𝟒 𝒎𝒐𝒍.𝑲
)

Classification of Dispersed System

1. True solution <1 nm
2. Colloidal dispersion 1 nm –0.5 μm
3. Coarse dispersion larger than 0.5 μm (emulsions and suspensions)

SOLUTIONS
o A mixture of two or more components that form a homogenous molecular dispersion or one-phase system
(Particle size: <1 nm)

Solvent – phase of the solution; usually constitutes the largest proportion of the system

o Protophilic or basic solvent

 Proton-accepting (acetone, ether, and liquid ammonia)

o Protogenic solvent
 proton-donating (formic acid, acetic acid, sulfuric acid, liquid HCl, and liquid HF)

o Amphiprotic solvents
 act as both (water and the alcohols)

o Aprotic solvents
 neither accept nor donate protons; neutral (hydrocarbon)

Solute – molecules or ions dispersed throughout the solvent

Non-electrolytes – do not yield ions in solution, no electric current
Electrolytes – forms ions in solution, conductor
 Weak (partial ionization)
 Strong (complete ionization)
Dissolution – transfer of molecules or ions from a solid state into solution
Solubility – extent of dissolution

Very soluble Less than 1 part

Freely soluble 1-10
Soluble 10-30
Sparingly soluble 30-100
Slightly soluble 100-1,000
Very slightly soluble 1,000-10,000
Practically insoluble More than 10,000 parts

Saturated solution – the solute is in equilibrium with the solid phase

Unsaturated or subsaturated solution –solute concentration is below necessary
Supersaturated solution – solute concentration is above necessary

Solubility can also be expressed in terms of molality, molarity, and percentage strength.
Molality – no. of moles of solute in 1 kg of solvent
Molarity – no. of moles of solute in 1 L of solution
Percentage strength – signifies the no. of grams of solute per 100 g of solution

Factors that affect Solubility

1. Temperature
 Endothermic dissolution - heat is absorbed, ↑ temp, ↑ solubility
 Exothermic dissolution - heat is released, ↓ temp, ↑ solubility (CaOH)

2. pH – Critical pH (pHc) or the pH of precipitation (pHp)

 Critical pH for a weak acid - pH below which WA precipitates from solution undissociated
 Critical pH for a weak base - pH above which WB precipitates from solution undissociated

3. Presence of Salts
 Salting-in (added salt increases hydrophilicity of the solution)
 Salting-out (added salt reduces the available amount of water  solute precipitates)

4. Particle Size
5. Concentration
6. Pressure (Henry’s Law)
COLLIGATIVE PROPERTIES OF SOLUTIONS
Colligative Property Notes Formula
Vapor Pressure Lowering  The addition of a non-volatile solute lowers Raoult’s Law – lowering of a vapor
the VP of a liquid pressure of a solvent is equal to the
 A liquid in a closed container will establish product of the mole fraction of the
an equilibrium with its vapor solute and vapor pressure of the solvent
 When equilibrium is reached, vapor exerts a
pressure (vapor pressure) – 𝜟𝑷 = 𝑷° × 𝒎𝒐𝒍𝒆 𝒇𝒓𝒂𝒄𝒕𝒊𝒐𝒏
VOLATILE – exhibits VP
NONVOLATILE – no measurable VP

Boiling Point Elevation BP – temp at which liquid pressure is equal to ∆𝑇𝑏 = 𝐾𝑏 𝑚

atmospheric pressure (1 atm = 760 mmHg)
𝟏𝟎𝟎𝟎 𝒘𝟐
∆𝑻𝒃 = 𝑲𝒃
The boiling point of a solution containing a non- 𝒘𝟏 𝑴𝑾𝟐
volatile solute would be higher than the pure
solvent because the solute would lower the Kb = ebullioscopic/molal BPE constant
vapour pressure of the solvent (0.52 °C/m)
m = molality
w1 = weight of solvent
w2 = weight of solute
MW2 = molecular wt of solute
Freezing Point Depression FP – temp at which the solid and liquid phases ∆𝑇𝑓 = 𝐾𝑓 𝑚
are in equilibrium under an external pressure
𝟏𝟎𝟎𝟎 𝒘𝟐
∆𝑻𝒇 = 𝑲𝒇
In general, solutions have a lower freezing point 𝒘𝟏 𝑴𝑾𝟐
than the pure solvent
Kf = cryoscopic/FPD constant
Applications: (Kf = 1.86°C/m)
 Salt is spread on roads to melt ice
 Ethylene glycol as “anti-freeze”
Osmotic Pressure Osmosis – movement of water across a
semipermeable membrane from low to high 𝝅𝑽 = 𝒏𝑹𝑻 𝑜𝑟 𝝅 = 𝑴𝑹𝑻
concentration
π = osmotic pressure in atm
This is the pressure required to offset the V = volume in L
movement of solvent thru a s. membrane n = no of moles of solute
𝐿.𝑎𝑡𝑚
Also defined as the pressure required to prevent R = gas constant (0.08205 )
𝑚𝑜𝑙.𝐾
osmosis in solutions. T = absolute temperature

Hypertonic – causes crenation

Hypotonic – causes swelling/lysis
Isotonic – 0.9% (w/v) NaCl
METHODS OF ADJUSTING ISOTONICITY
Class I: Addition of a tonicity adjusting agent
1. Freezing Point Depression Method/Cryoscopic
 Isotonic freezing point depression – 0.52°C

2. Sodium Chloride Equivalent Method/E Value

 E value – gram of NaCl equivalent to 1 gram of a substance
Step 1. Calculate the amount of NaCl represented by the ingredients
Step 2. Calculate the amount of Nacl that would make the volume of solution specified isotonic
Step 3. Subtract Step 1 from Step 2.
Step 4. If agent other than NaCl (boric acid, dextrose, Na or K nitrate), divide the amount of NaCl
(Step 3) by the NaCl equivalent (E value) of the other substance.

Class II: Addition of water and dilution with buffered isotonic solution
1. White Vincent Method
𝑽𝑯𝟐𝑶 = 𝒘𝒕 × 𝑬 𝒗𝒂𝒍𝒖𝒆 × 𝟏𝟏𝟏. 𝟏

2. Sprowl’s Method – simplified White Vincent method

𝑽𝑯𝟐𝑶 = 𝟎. 𝟑 × 𝑬 𝒗𝒂𝒍𝒖𝒆 × 𝟏𝟏𝟏. 𝟏

ACID-BASE EQUILIBRIA
Ionization – complete separation of ions in a crystal lattice when salt is dissolved
Dissociation – separation of ions in solution when the ions are associated by interionic attraction

Theory Acid Base

+ + -
Arrhenius Yields H or H3O OH
Bronsted-Lowry Theory Proton donor Proton acceptor
-
Lewis Theory E acceptor E- donor
Pearson’s HSAB Hard acids are e- acceptor with high positive
charges and relatively small sizes while soft
acids have positive charges and relatively small

pH – the negative logarithm of the H+ concentration

𝒑𝑯 = −𝒍𝒐𝒈 [𝑯+]

Sorensen’s pH scale
Neutral = 7
Acidic < 7
Basic > 7

For weak acids 𝐻𝐴 + 𝐻2 𝑂 ↔ 𝐻3 𝑂+ + 𝐴−

For weak bases 𝐵 + 𝐻2 𝑂 ↔ 𝑂𝐻 − + 𝐵𝐻 +
Water Ionization 𝐻2 𝑂 + 𝐻2 𝑂 ↔ 𝐻3 𝑂+ + 𝑂𝐻 −
pH Calculations

Strong Acids 𝒑𝑯 = −𝒍𝒐𝒈 [𝑯+]

Strong Bases 𝑝𝐻 = −𝑙𝑜𝑔 [𝑂𝐻 −] or 𝒑𝑯 = 𝟏𝟒 − (−𝒍𝒐𝒈 [𝑶𝑯− ])

1
Weak Acids 𝑝𝐻 = 2 𝑝𝐾𝑎 − 𝑙𝑜𝑔𝐶𝑎

𝑏𝑎𝑠𝑒 1
Weak Bases 𝑝𝐻 = 𝑝𝐾𝑤 − 𝑝𝐾𝑏 + 𝑙𝑜𝑔 𝑠𝑎𝑙𝑡
or 𝑝𝐻 = 𝑝𝐾𝑤 − 2 (𝑝𝐾𝑏 − 𝑙𝑜𝑔𝐶𝑏)

BUFFERS
 Solutions that have the property of resisting changes in pH when acids or bases are added to them
 This property results from the presence of a buffer pair which consists of either:
- Weak acid and some salt of a weak acid or its conjugate base
- Weak base and some salt of a weak base or its conjugate acid

Henderson-Hasselbach Equation

𝑠𝑎𝑙𝑡
Weak acids 𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔
𝑎𝑐𝑖𝑑

𝑏𝑎𝑠𝑒
Weak bases 𝑝𝐻 = 𝑝𝐾𝑤 − 𝑝𝐾𝑏 + 𝑙𝑜𝑔 𝑠𝑎𝑙𝑡

Buffer Capacity (Buffer action/Buffer efficiency/Buffer index/Buffer value)

 Ability of a buffer solution to resist changes in pH

Approximate formula
[𝒔𝒂𝒍𝒕]+[𝒃𝒂𝒔𝒆]
𝒑𝑯 = 𝒑𝑲𝒂 + 𝒍𝒐𝒈 [𝒂𝒄𝒊𝒅]−[𝒃𝒂𝒔𝒆]

Exact formula/Koppel-Spiro Van Slyke’s Equation

𝑲𝒂 [𝑯𝟑 𝑶+]
𝜷 = 𝟐. 𝟑𝑪 (𝑲 + 𝟐
𝒂 +[𝑯𝟑 𝑶 ])

Where C = total buffer concentration, that is, the sum of the molar concentrations of the acid and the salt.

Maximum Buffer Capacity

- occurs when pH = pKa
- 𝜷𝒎𝒂𝒙 = 𝟎. 𝟓𝟕𝟔 𝑪
INTERFACIAL PHENOMENA
o Attributed to the effects of the molecules found at the interface between 2 phases
o Interfacial Tension (L-L)
o Surface Tension (S-L, L-G)

Surfactants
 Surface active agents
 Lowers the interfacial/surface tension
 Griffin HLB System (higher-hydrophilic, lower lipophilic)
Anti-foaming 1-3
W/O 3-8
Wetting agent 7-9
O/W 8-16/9-12
Detergent 13-16
Solubilizer 16-19

Absorption - entry into the system

Adsorption - adherence to surface
Adsorption Isotherm Theories:
 Freundlich Isotherm
- Adsorption of gas is infinite
- ⬆P, ⬆adsorption
 Langmuir Isotherm
- Limited adsorption
- Monomolecular layer is formed
- the amount of adsorbate on the adsorbent as a function of its pressure (if
gas) or concentration (if liquid) at constant temperature.
Cohesion - same molecules
Adhesion - different molecules
Capillarity - tendency to rise up a normal tube
Wetting - made by liquid or solid surface | ⬆contact angle, ⬇wettability | 0° - complete wettability
 COLLOIDAL DISPERSION
 A system having a particle size intermediate between that of a true solution and a coarse dispersion
 colloidal system, solution, dispersion, aerosols, emulsions, foams, hydrosols
 1nm – 0.5mc

CLASSES
1. Lyophilic
 Spontaneous
 Thermodynamically stable

2. Lyophobic
 Nonspontaneous
 Thermodynamically unstable

3. Association colloids/Amphiphilic colloids

 Involves surfactants which can accumulate and form a micelle (colloidal sized particles)

METHODS OF PREPARATION
1. Condensation
 Principle: small particles –(condensed)colloidal particles

2. Deflocculation /Dispersion
 Principle: bigger particle –(broken down)colloidal particles

3. Peptization
 Similar to the principle of salting-out
 (+) electrolyte solution will cause the precipitation of colloidal sized particles

PROPERTIES
1. Optical
 Faraday-Tyndall Effect – ability to scatter or disperse light (foggy street)

2. Kinetic
 Brownian motion – colloidal particles appear as tiny points of light in constant motion when examined
under an ultramicroscope

 Diffusion – spontaneous movement of particles from a region of higher concentration to one of lower
concentration until equilibrium is achieved

3. Electric
 Nerst Potential / Electrothermodynamic potential
- difference in potential between the actual surface of the particle and the electroneutralregion of
the dispersion

 Zeta Potential / Electrokinetic Potential

- difference in potential between the surface of the tightly-bound layersand the
electroneutralregion of the dispersion (⬇zeta potential results to flocculation)
 COARSE DISPERSIONS
 A system with particles being larger than 0.5 mcm
 Emulsions and suspensions

SUSPENSION – insoluble particles are dispersed in a liquid medium (< 0.1 nm)

Properties of Suspended Particles:

Sedimentation rate Settling
Deflocculated Slower “hard cake”
Flocculated Faster -
dispersed
Instability of Suspensions

a. Aggregation - globules come together but do not fuse (aka agglomeration)

b. Sedimentation - downward monevent
c. Caking

EMULSIONS

Instability of Emulsions

a. Flocculation - formation of lumps

b. Creaming - upward or downward movement of the internal phase
c. Coalescence - globules come together and fuse
d. Cracking - total separation of two phases)
e. Breaking
f. Phase inversion

SEMISOLIDS

Gel – consists of a condensed mass enclosing and interpenetrated by a liquid

Jelly – coherent matrix is rich in liquid
Xerogel – liquid is removed, framework remains

Instability of Gels
e. Syneresis - shrinking, some liquid is pressed out
f. Bleeding - liberation of oil or water due to deficient gel structure
g. Swelling - taking up of liquid with volume increase
h. Imbibition - taking up of liquid without volume increase
 RHEOLOGY
o Scientific study of the deformation and flow properties of matter
o Elasticity, fluidity (ɸ), viscosity (ɳ) and plasticity

Viscosity (ɳ)
1. Resistance to flow
2. Reciprocal of fluidity; ɳ = 1/ɸ
3. Ratio of the shear stress (F) to the shear rate (G)
4. = where: F is shear stress (force per unit area); G is shear rate (velocity gradient)

CLASSES
1. Absolute viscosity =
 Units: poise (dyne sec/cm2 or g/cm sec) or centipoises
 Using capillary viscometer:
𝟏 𝒑𝟏 𝒕𝟏
=
𝟐 𝒑𝟐 𝒕𝟐

2. Kinematic viscosity = 𝒏 𝒑𝟏𝒕𝟏

 units: stokes(s); centistokes(cs)

3. Relative viscosity (ɳrel) = 𝒏𝟏 𝒏𝟐

VISCOMETERS
1. Ostwald viscometer (Modern adaptation: Ostwald-Cannon-Fenske Viscometer)
2. Falling Sphere Viscometer (Hoeppler Falling-ball Viscometer)
3. Cup-and-bub Viscometer
 Courette type (Mac Michael Viscometer)
 Searle Type (Rotovisco Viscometer, Stormer Viscometer, Brookfield Viscometer)
4. Cone-and-Plate Viscometer
5. Ferranti-Shirley Cone-and-Plate Viscometer
FLOW SYSTEMS
1. Newtonian Flow
 Has linear relationship between shear rate and shear stress
 Constant viscosity with increasing rate
 Eg: ethanol, water, acetone, glycerin, benzene

2. Non-Newtonian Flow
Shear-Dependent Viscosity
Plastic
- Simplest type of non-Newtonian behavior in which the curve is linear only at values ofF,
beyond its yield value.
- Yield value is the force that should be exceeded for a bingham body (plastic) to flow
- Eg: gels, ointments, margarine
Pseudoplastic
- Non-linear; “shear-thinning”
- ⬆G (shear rate); ⬇ ɳ
- Eg: catsup and toothpastes

Dilatant
- Non-linear; “shear-thickening”
- When stress is removed, a dilatant system returns to its original state of fluidity.
- ⬇G, ⬆ ɳ
- Eg: paint, starch paste

Time-Dependent Viscosity
Thixotropy
- Breakdown of structure (shear-thinning) that does not reform immediately when stress is
removed or reduced
- Thixotropy is an isothermal and comparatively slow recovery (on standing of a material) of a
consistency lost through shearing
- ⬆time, ⬇ ɳ
- Shows a hysteresis loop, that is, the curve obtained on increasing shear stress is not
superimposable with that obtained on decreasing shear stress.

Rheopexy
- A phenomenon in which a solid forms a gel more readily when gently shaken or otherwise
sheared than when allowed to form the gel while the material is kept at rest
- ⬆time, ⬆ɳ
SOLIDS
o Characterized of having fixed shapes, nearly incompressible
o Have strong intermolecular forces, very little kinetic energy
o Their atoms vibrate in fixed positions about an equilibrium position, there is very little translationalmotion

CRYSTALLINE
 The molecules or atoms are arranged in repetitious three-dimensional lattice units
 Solvates –aka “pseudopolymorphs”; crystals having solvent molecules
 Types based on geometric forms
Cubic -NaCl
Tetragonal –Urea
Hexagonal –Iodoform
Rhombic –Iodine
Monoclinic –sucrose
Triclinic -boric acid

Types based on forces of attraction

1. Covalent crystals – covalent bond (diamond, graphite, quart)
2. Ionic crystals – (NaCl)
3. Molecular crystals – Van der Waals & H-bonding (sucrose, ice)
4. Metallic crystals – solid in their elemental forms (elemental iodine)

Properties
 Polymorphism- a solid may exist in more than one crystalline form
 Example: theobroma, cocoa butter
Form Melting Point (in °C)
Gamma (most unstable) 18
Alpha 22
Beta’ 28
Beta (most stable) 34.5

Polymorphic Changes & Properties

Enantiotropic Change is reversible
Monotropic Change is unidirectional
Isotropic Similar (identical) properties in all directions
Anisotropic Different Properties in various directions along the crystal

Amorphous Crystalline
 Random unoriented molecules  Fixed geometric patterns
 Glass and Plastics  Ice and NaCl
 Arranged in random manner  Orderly arranged units, incompressible
 No definite MP  Definite MP, pass sharply from solid to liquid
 MICROMERITICS
o Study of small particles
Types of Properties of Particles
Particle Sizes
1. Fundamental
Coarse >1000 μm
 Inherent in all individual particles
Conventional 50-1000 μm
 Eg: size, shape, density, volume Fine 1-50 μm
2. Derived Very Fine 0.1-1 μm
 Combination of fundamental properties Ultra-Fine <0.1 μm
 Eg: bulk density, granule volume, porosity

Methods of Determining Particle Size

1. Optical microscopy
 Use of microscope to measure individual particle
 Adv: individual particles can be seen
 Disadv: very tedious, 2D-image only

3 Measurements
 Ferret diameter – 2 tangents separated by the longest distant
 Martin Diameter – distance what will bisect the particle into halves
 Projected Area of the Circle – diameter of the circle that will enclose the particle

2. Sieve analysis
 USP method
 Sieve # (Mesh #) - number of openings per linear inch
 Disadv: attrition of particles

3. Sedimentation method
 Sedimentation rate or free fall velocity of particles
 Apparatus: AndreasenApparatus / Pipet
 Principle: Stoke’sLaw

4. Automatic particle counter

 Coulter counter - Principle: electric resistance (↑ER ↑PS)
 HIAC/Royco Instrument - Principle: Light blockade (↓light ↑PS)
 Gelman Counter - Principle: Faraday –Tyndall Effect
Particle Volume
𝑇𝑟𝑢𝑒 𝑣𝑜𝑙𝑢𝑚𝑒 = 𝑣𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝑝𝑎𝑟𝑡𝑖𝑐𝑙𝑒 ( 𝑝)
𝑟𝑎𝑛𝑢𝑙𝑒 𝑣𝑜𝑙𝑢𝑚𝑒 ( 𝑔) = 𝑝 + 𝑖𝑛𝑡𝑟𝑎𝑠𝑝𝑎𝑐𝑒
𝐵𝑢𝑙 𝑣𝑜𝑙𝑢𝑚𝑒 ( 𝑏) = 𝑔 + 𝑖𝑛𝑡𝑒𝑟𝑠𝑝𝑎𝑐𝑒𝑠

Particle Density
𝑇𝑟𝑢𝑒 𝑑𝑒𝑛𝑠𝑖𝑡𝑦 = 𝑚𝑎𝑠𝑠 𝑝
𝑟𝑎𝑛𝑢𝑙𝑒 𝐷𝑒𝑛𝑠𝑖𝑡𝑦 = 𝑚𝑎𝑠𝑠 𝑔
𝐵𝑢𝑙 𝑑𝑒𝑛𝑠𝑖𝑡𝑦 = 𝑚𝑎𝑠𝑠 𝑏

Porosity – measure of total voids/ spaces

𝑏− 𝑔
𝑖𝑛𝑡𝑒𝑟𝑠𝑝𝑎𝑐𝑒 = 𝑥 100
𝑏

𝑔− 𝑝
𝑖𝑛𝑡𝑟𝑎𝑠𝑝𝑎𝑐𝑒 = 𝑥 100
𝑔

𝑏− 𝑝
𝑡𝑜𝑡𝑎𝑙 = 𝑥 100
𝑏

Properties of Powders For Granulation

1. Fluidity
2. Compressibility

Angle of Repose
𝒉𝒆𝒊𝒈𝒉𝒕
= 𝒕𝒂𝒏−𝟏 𝒓𝒂𝒅𝒊𝒖𝒔

Carr’s Compressibility Index

𝑽𝒊 − 𝑽𝒇
𝑪 = 𝒙 𝟏𝟎𝟎
𝑽𝒊

𝒕𝒂𝒑𝒑𝒆𝒅 − 𝒃𝒖𝒍𝒌
𝑪 = 𝒙 𝟏𝟎𝟎
𝒕𝒂𝒑𝒑𝒆𝒅

Hausner’sRatio
𝑯𝑹 = 𝑽𝒐 𝑽𝒇
𝑯𝑹 = 𝒕𝒂𝒑𝒑𝒆𝒅 𝒃𝒖𝒍𝒌
 PHASE EQUILIBRIA
Phase Diagram
o Represents the states of matter that exist as temperature and pressure are varied.
o It is a graphic way to summarize the conditions under which equilibria exist between the different states of
matter.
o Such a diagram also allows us to predict which phase of a substance is present at any given temperature and
pressure.

Latent Heat/ Molar Heat

 Heat necessary for 1 mole of a gas, solid or liquid to change to another phase
 Either gained or lost
 NOTE: without latent heat, no phase transition

Molar Heat of Fusion (ΔHf) - Heat required to convert 1 mole of solid to liquid
Molar Heat of Sublimation (ΔHs) - Heat required to convert 1 mole of solid to gas
Molar Heat of Vaporization (ΔHv) - Heat required to convert 1 mole of a liquid to gas

Gibb’s Phase Rule

 Used to determine the number of independent variables (temperature, pressure, concentration) that must be
set in order to define a system
 F = C –P + 2 (1 component system)
 F = C –P + 1 (2 component system)
 F = C –P (3 component system)
 F: Degrees of Freedom
 C: number of Components
 P: number of Phases
One Component System
 Eg: water
 Calculate F.
 G; L; S bivariant
 G-L; L-S; G-S univariant
 G-L-S invariant

Two-Component System
 Aka Condensed system
 System in which vapour phase is ignored and only the solid and/or liquid phases are considered

Liquid-Liquid System
 Binodal curve
- area within the curve represents a two phase system; Any point beyond it is a single phase
 Critical solution temperature (upper consolute temperature)
- temperature beyond which every proportion of A & B will exist as 1-phase; maximum temperature to
obtain a one phase system
 Tie Line
- line from which a system separates into phases of constant composition; used to approximate the
proportions of components A & B existing at a particular temperature
 Conjugate phases
- phases of constant composition that separate when a mixture is prepared within the boundary of the
2-phase system

The Lever Arm Rule

𝒘𝒕 𝒐𝒇 𝒑𝒉𝒂𝒔𝒆 𝒍𝒆𝒏𝒈𝒕𝒉 𝒐𝒇 𝒐𝒑𝒑𝒐𝒔𝒊𝒕𝒆 𝒂𝒓𝒎

=
𝒘𝒕 𝒐𝒇 𝒑𝒉𝒂𝒔𝒆 𝒍𝒆𝒏𝒈𝒕𝒉 𝒐𝒇 𝒐𝒑𝒑𝒐𝒔𝒊𝒕𝒆 𝒂𝒓𝒎

Solid-Liquid System

 Eutectic Point
- Is the point where solid A, solid B and the liquid phase co-exist
- 3-phases co-exist
 Eutexia
- phenomenon of lowering the melting point due to combinations of components (thymol-salol;
camphor-menthol)

Three Component System

1. Ternary system
2. Temperature are pressure are both made constant
3. Consists of two liquids that are partially miscible to each other and the third component acts as co-solvent
which has the affinity to both immiscible layers
4. Phase Rule: F = C –P
5. Apex - 100% of each component
6. Base - opposite of apex; 0% of each component
 CHEMICAL KINETICS
o Study of the rates of reactions and the mechanism by which these reactions occur
o Application in pharmacy: stability and bioavailability of pharmaceutical products

Rate of Reaction / Degradation Rate

- Velocity with which the reaction occurs
- Depends on:
 Reactant concentration
 Temperature
 pH
 presence of solvents or additive

Order of Reaction – the way in which the concentration of the drug or reactant in a chemical reaction affects rate

Zero-order Reaction
- the drug concentration changes with respect to time at constant rate
- the rate of reaction is independent of the concentration of the reactants 𝑪 = −𝒌𝟎 𝒕 + 𝑪𝟎
- eg. Alcohol, aspirin, phenytoin

First-order Reaction
𝑪 = 𝑪𝟎 𝒆−𝒌𝒕
- the rate of reactions dependent on the concentration of drug remaining
or
- most drugs follow this reaction
- Ex: t1/2: 2 hrs
𝒍𝒏𝑪 = −𝒌𝒕 + 𝒍𝒏𝑪𝟎

Second-order Reactions
- reaction is dependent on the squared amount of drug remaining
- no application in pharmaceutical dosage form

Half-life (t ½ )
- the period of time required for the amount or concentration of a drug to decrease by one-half or 50%. the time
required for one-half of the material to disappear
Order Half-life Equation
𝟎. 𝟓𝑪𝒐
Zero
𝒌
𝟎. 𝟔𝟗𝟑
First
𝒌
𝟏
Second
𝑪𝒐𝒌

Shelf-life (t90)
- “expiration-dating period”
- the period of time where 90% of the original concentration is left and 10% is already degraded
𝟎.𝟏𝟎𝟓
- 𝑻𝟗𝟎 =
𝒌
 S1 Dealer
S2 Prescriber
S3 Retailer
S4 Wholesaler
S5-I Importer
S5-C Compounder
S6 Researcher
S7 Importer & Compounder

*Renewal: not later than Jan. 31

Jurisprudence
“system of laws”
“science of philosophy of laws”

ETHICS
“science of morality”
“moral principles of practice”
 RA Name Date
5921 Pharmacy Law (EO 174) June 23 1969
3720 Foods, Drugs, Devices, and Cosmetics Act (EO 175) June 22 1963
8203 Special Law on Counterfeit Drugs
6425 Dangerous Drugs Act March 30 1972
9165 Comprehensive Dangerous Drugs Act June 7 2002
953 Narcotics Drug Law June 20 1953
9211 Tobacco Regulation Act June 23 2003
6675 Generics Act of 1988 Sep 13 1988
7432 Senior Citizens Act 2.7 & 4.23 1992
9257 Expanded Senior Citizens Act Feb 26 2004
9994 Expanded Senior Citizens Act of 2010 Feb 15 2010
7876 Senior Citizen Center Act Feb 14 1995
8423 TAMA (Traditional and Alternative Medicines Act) Dec 9 1997
7581 Price Act May 27 1992
9502 Cheaper and Quality Medicines Act of 2008 June 6 2008
9184 Procurement Act Jan 10 2003
7394 Consumer Act April 13 1992
9711 FDA Act of 2009 Aug 18 2009
8981 PRC Modernization Act Dec 5 2000
8172 ASIN Dec 20 1995
8293 Intellectual Property Code Jun 6 1997

AO Name Date
220 cGMP (AO 43 – cGMP for DRUGS) June 13 1974
79 Transitional Remedial Labeling Sep 18 1989
184 Registration of Herbal Products (AO 42)
172 Registration of Herbal Medicines (AO 42)
62 Prescribing Requirements March 15 1989
63 Dispensing Requirements March 16 1989
55 Labeling of Pharmaceuticals Dec 7 1988
56 Licensing of Drug Establishments and Outlets Jan 3 1989
51 Compliance of 6675

EO Name Date
851 Creation of BFAD June 22, 1973
266 Institutionalization of CPE July 25, 1995
174 Latest Amendment of 5921
175 Latest Amendment of 3720
119 Reorganization of BFAD
302 Philippine Pharmacopoeia

PD Name Date
223 Creation of PRC June 22, 1973
907 Honor Graduate Eligibility March 11, 1976
1926 54 years Baccalaureate Study
1363 RE: Citizenship Requirement for PLE
RA 5921 (as amended by EO 174) THE PHARMACY LAW
AN ACT REGULATING THE PRACTICE OF PHARMACY AND SETTING STANDARDS OF PHARMACEUTICAL
EDUCATION IN THE PHILIPPINES AND FOR OTHER PURPOSES

Objectives (a) the standardization and regulation of pharmaceutical education

(b) the examination for registration of graduates of schools of pharmacy and
(c) the supervision, control and regulation of the practice of pharmacy in the Philippines

Composition of CHED Secretary: Patricia Licuanan

Council of DOH Undersecretary: Enrique Tayag
Pharmaceutical BFAD Director: Kenneth Hartigan Go
Education PACOP President: Vicky Mendoza
BOP Chairman: Mildred Oliveros
PPhA Chairman: Olivia Limuaco
UP Dean: Imelda Pena
Dean Private Colleges
PRC Board of Chairman and two members with a 3 year term:
Pharmacy (a) Natural born citizen of the Philippines;
(b) Registered and practicing for at least 10 years;
(c) Of GMC and of recognized standing in the pharmaceutical profession;
(d) At the time of appointment, not a member of the faculty of any pharmacy school
(e) A member of any national pharmaceutical association of the Philippines.

RA 3720 (as amended by EO 175) FOODS, DRUGS, AND COSMETICS ACT

AN ACT TO ENSURE THE SAFETY AND PURITY OF FOODS, DRUGS, AND COSMETICS BEING MADE
AVAILABLE TO THE PUBLIC BY CREATING THE FOOD AND DRUG ADMINISTRATION WHICH SHALL
ADMINISTER AND ENFORCE THE LAWS PERTAINING THERETO, AND FOR OTHER PURPOSES

Objectives (a) Establish standards and quality measures for food, drug, and cosmetic.
(b) Adopt measures to insure pure and safe supply of food, drug, and cosmetics
(c) Adopt measures to ensure rational use of drugs and services
(d) Strengthen the BFAD
*includes definitions of adulterated and misbranded drugs and devices
BFAD Functions (a) Administer and supervise the implementation of this Act and of the rules and regulation
(b) Provide for the collection of samples of food, drug and cosmetic
(c) Analyze and inspect food, drug and cosmetic
(d) Establish analytical data to serve as basis for the preparation of food, drug and cosmetic standards,
and to recommend standards of identity, purity, quality and fill of container
(e) Issue certificate of compliance
(f) Levy, assess & collect fees for inspection, analysis and testing of products & materials
(g) Certify batches of anti-biotic and anti-biotic preparations

BFAD Divisions (a) Inspection and Licensing Division

(b) Laboratory Division
AO 56 s of 1989
REVISED REGULATIONS FOR THE LICENSING OF DRUG ESTABLISHMENTS AND OUTLETS

Types of Drug Drug Manufacturer

Establishments Drug Trader
Drug Distributor/Importer Drug Distributor/Exporter
Drug Distributor/Wholesaler
Requirements for A. Premises
Drug Outlets  Signboard in front of the place of business bearing registered name of drug store
 A well-ventilated area not less than 15 sq. m. with concrete, tile or wooden flooring
 A place suitable for compounding prescription and for washing and sterilizing bottles
(compulsory only for hospital pharmacy).
 A suitable and proper place for the adequate storage of drugs and biological products as
specified on the label
 A suitable cabinet for keeping poisons and/or dangerous drugs
 An adequate water supply

B. References/Documents
 Philippine National Drug Formulary (when available)
 United States Pharmacopeia/National Formulary (USP-NF) (latest edition)
 R.A. 3720, R.A. 6675, R.A. 5921
 Remington’s Pharmaceutical Sciences (latest edition)
 Goodman & Gilman — Pharmacological Basis of Therapeutics (latest edition)

C. Record Books Registered with BFAD

 Prescription Book
 Dangerous Drug Book
 Exempt Preparation Book
 Poisons Book
 Record Book for Selected Non-Prescription Drugs

RA 6425 THE DANGEROUS DRUGS ACT

RA 9165 COMPREHENSIVE DANGEROUS DRUGS ACT
Dangerous Drugs Prohibited Drug
Opium and its derivatives, Coca leaf and its derivatives

Regulated Drug
Barbiturates, Benzodiazepines, Amphetamine, such as benzedrine or Dexedrine, Methaqualone

Records Required Original record of sales, purchases, acquisitions and deliveries of dangerous drugs, indicating therein
of RPh the license number and address of the pharmacist; the name, address and license of the
manufacturer, importer or wholesaler from whom dangerous drugs have been purchased; the
quantity and name of the dangerous drugs so purchased or acquired; the date of acquisition or
purchase; the name, address and class A residence certificate number of the buyer; the serial number
of the prescription and the name of the doctor, dentist, veterinarian or practitioner issuing the same;
the quantity and name of the dangerous drug so sold or delivered; and the date of sale or delivery.

A certified true copy of such record covering a period of three calendar months, duly signed by the
pharmacist or the owner of the drug store or pharmacy, shall be forwarded to the city or municipal
health officer within fifteen days following the last day of every quarter of each year.
RA 6675
AN ACT TO PROMOTE, REQUIRE AND ENSURE THE PRODUCTION OF AN ADEQUATE SUPPLY,
DISTRIBUTION, USE AND ACCEPTANCE OF DRUGS AND MEDICINES IDENTIFIED BY THEIR GENERIC
NAMES

Prohibited Acts:
1. Code - system of words to represent words
2. Cipher - method of secret writing
3. Secret Keys - confidential to one or few

Components of 1. Quality Assurance of Drugs

the National 2. Rational Use of Drugs by Health Professionals and Consumers
Drug Policy 3. National self-sufficiency in Pharmaceuticals
4. Rationalization of the DOH’s Procurement Program
AO 62 s of 1989 RULES AND REGULATIONS TO IMPLEMENT PRESCRIBING REQUIREMENTS UNDER THE
GENERICS ACT OF 1988
 Generic names shall be used
 Generic name must be written in full but salt may be abbreviated
 Generic name must be clearly written on the prescription immediately after Rx
 Brand name should be in parentheses and under generic name

Violative Prescriptions
 generic name is not written;
 generic name is not legible, brand name is legible
 brand name is indicated and instructions added, such as 'No Substitution'

Impossible Prescriptions
 only generic name is written but illegible
 generic does not correspond with the brand
 both generic and brand are not legible
 product not registered with BFAD

Erroneous Prescriptions
 brand name precedes the generic name
 generic name is the one in parenthesis
 brand name is not in parenthesis
 more than one drug product is prescribed in one prescription form

AO 63 s of 1989 RULES AND REGULATIONS TO IMPLEMENT DISPENSING REQUIREMENTS UNDER THE

GENERICS ACT OF 1988
 Generic dispensing – dispensing the patient’s choice from among generic equivalents
 Inform the patient of all available drug products generically equivalent to the prescribed drug
 All drug outlets shall post in a conspicuous place in their establishment a list of drug products
using their generic and brand names

RA 7432 SENIOR CITIZENS ACT 65 y.o 20% + 12% VAT

RA 9257 EXPANDED SSA 65 y.o 20% non-VAT
RA 9994 EXPANDED SSA of 2010 60 y.o 20% non-vat