Name: Alternative Products if Patients cannot Swallow an Intact Solid

Dosage Form
Pharmaceutical Dosage
 Chewable tablet
Chapter 7: Capsules  Instant dissolving tablet
 Oral liquid
Capsules and Tablets  Oral or nasal inhalation solution
 Suppository
 Preferred when administered orally by adults: conveniently  Injection
carried, readily identified, easily taken
 Variety of dosage strengths, providing: Characteristics
 Flexibility to the prescriber
 Accurate individualized dosage for the patient  May be swallowed whole by patient
 May be inserted into the rectum for drug release and
Pharmaceutical Standpoints
absorption from site
 The content may be removed from the gelatin shell and
 Solid dosage forms:
employed as pre measured medicinal powder, the capsule
 Manufactured efficiently and productively
shell being use to contain a dose of the medicinal
 Packaged and shipped at lower cost and with less
substance.
breakage
 Ex: Theo-dur Sprinkle
 More stable
 Elegance
 Have longer shelf life than liquids
 Ease of use
Disadvantages of Tablets and Capsules  Portability
 Tasteless shell to mask the unpleasant taste/ odor
 Swallowing  Permits physician to prescribe the exact medication needed
 Formulation difficulties buy the patient
 Some have poor bioavailability or poor water solubility  Conveniently carried
 Some have irritant effect on the GIT when taken orally  Readily identified
 Easily taken
Key Features of a Good Tablet or Capsule  Tasteless when swallowed
 Commonly embossed or imprinted on their surface the
 Stability of the active drug manufacturer’s name and product code readily identified
 Accurate dose  Available in variety of dosage strength
 Uniformity (weight, amount of active ingredient, coating  Provide flexibility to the prescriber and accurate
thickness, etc) individualized dosage for the patient
 Consistent performance (manufacturing parameters,  Packaged and shipped by manufacturers at lower cost, less
pharmacokinetics) breakage than liquid forms
 Appropriate disintegration and dissolution  More stable and longer shelf life
 Can withstand packaging, shipping, handling without
breakage Hard Gelatin Capsules
 Masking of taste and odor
 Pharmaceutically elegant  Also referred to as “DFC” Dry Filled Capsule,
 Production economically sound manufactured into two sections, the capsule body and a
shorter cap
Overview of Capsules  Manufacture most of the commercially available medicated
capsules
 Capsules  Employed in clinical drug trials
 Medicinal agents and/or inert substances  For extemporaneous compounding of
enclosed in a small shell of gelatin prescriptions
 Swallowed wholly  Contains 13% to 16% moisture
 Open capsule or crushed tablets  Manufactured form:
 Mixed with food or drink (children or patients  Gelatin
who are unable to swallow solid dosage forms)  Titanium dioxide (opacifying agent)
 0.15% SO2 (prevents decomposition of gelatin)
Solid Dosage Forms that must be Left Intact  Colorants

 Enteric coated tablets Empty Capsule Shells

 To pass through the stomach for drug release and
absorption in the intestine  Made of gelatin, sugar and water
 Extended-release dosage forms  Hard or soft
 Provide prolonged release of the medication  Softened (made elastic or plasticized) by adding glycerin or
 Sublingual or buccal tablets polyhydric alcohol like sorbitol)
 To dissolve under the tongue or in the mouth  Can be: clear, colorless, tasteless
 Colored with various FD&C and D&C dyes

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  Made opaque by adding agents like titanium oxide  Magnesium stearate
 Stearic acid or talc (about 0.25-1%)
Gelatin  Surface active agent (surfactant)
 To facilitate wetting by GI fluids
 Obtained by partial hydrolysis of collagen from the skin,  Sodium lauryl sulfate
white connective tissue and bones of animals
 Properties: Fixed or Volatile Oils
 Stable in air (dry)
 Subject to microbial decompositions when  Do not interfere with stability of the gelatin shells
moistened
 Insoluble in cold water, softens through Eutectic Mixture of Drugs
absorption of up to 10 times its weight of water
 Soluble in hot water and in warm gastric fluid  Mixtures of agents that have a propensity to liquefy when
 A protein, digested by proteolytic enzymes and admixed
absorbed
 High humidity: additional moisture is absorbed Methods to Track the Passage of Capsules and Tablets through the
 Becomes distorted and lose their rigid GIT to Map their Transit Time and Drug Release Patterns
shape
 Remedy: use desiccant material (silica  Gamma scintigraphy
gel, slay, or activated charcoal)  Gamma ray emitting radiotracer incorporated into
 Extreme dryness: moisture is lost the formulation with gamma camera coupled to a
 Becomes brittle and crumble when data recording system
handled  Pharmacoscintographic evaluation
 IVIVC for bioavailability of immediate release
Gelatin Capsule products
 Combination of scintigraphy and pharmacokinetic
 Dissolves and exposes its contents studies
 Unsuitable for aqueous liquids (softens gelatin and  Assesses integrity and transit of time of enteric
distorted, resulting in leakage of contents) coated tablets through the stomach to the
intestines
Additives  Drug and dosage form evaluation in new product
development
 Desiccant  Heidelberg capsule (No. 0 gelatin capsule)
 To protect against the absorption of atmospheric  pH sensitive (non indigestible radio telemetric
moisture device)
 Dried silica gel  A non-radioactive means to measure solid dosage
 Clay forms (fasting and non fasting human subjects)
 Activated charcoal  Gastric pH, gastric emptying time,
 Diluents or filter gastric residence time
 To produce the proper capsules fill volume
 Provide cohesion to the powders Manufacture of Hard Gelatin Capsule Shells
 For the transfer of the powder blend into the
capsule shells  Manufactured in 2 sections:
 Lactose  Capsule body
 Microcrystalline cellulose  Shorter cap
 Starch
Drug Absorption Depends on a Number of Factors
Excipients Added for Capsule Fill
 Solubility of the drug
 Wetting agents (Li2CO3)  Type of product formulation (immediate release, modified
 Added to capsule formulation to enhance drug enteric)
dissolution  Gastrointestinal contents
 Absorbent  Physiologic character and response
 Separates interacting agents
 Absorbs any liquefied material that may form Innovations to Provide Distinctions (Distinctive Looking Capsules)
 Magnesium carbonate
 Kaolin or light MgO  Pulvules
 Disintegrants  End of the body-producing peg is tapered while
 To assist the break up and disintegration of the leaving the cap-making peg rounded
capsule’s contents in the stomach  Spansule capsules
 Pregelatinized starch  Capsules with the ends of both the bodies and
 Croscarmellose caps highly tapered
 Sodium starch glycolate
 Lubricant or glidant Innovations in Capsule Shell Designs
 Enhances flow properties
 Silicon dioxide  Snap-fit
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  Two halves of capsule shells positively joined  Lack of homogeneity for low dose drugs
through locking grooves in the shell walls  Results in significant therapeutic consequences
 Ensure reliable closing of the filled capsule
 Coni-snap Preformulation Studies
 Rim of the capsule body is tapered slightly, not
straight  Determine whether all of the formulation’s bulk powders
 Reduces the risk of the capsule rims touching or  Effectively blended together
joining  Require reduction of particle size
 Eliminates splitting (telescoping) and/or denting  Other processes to achieve homogeneity
of capsule shell
 Coni-snap supro Methods in Reducing Particle Size
 Rim is tapered, upper capsule part extends
(rounded edge of lower surface is visible)  Milling
 Opening is difficult, lower surface less gripping  Particles ranging from 50-1000 micrometer
to pull 2 halves apart  Micronization
 Increases security of contents and integrity of the  Drugs of lower dose or when smaller particles are
capsule required
 Eliminates splitting (telescoping) and/or denting  Particles ranging from 1-20 micrometer
of capsule shell
Filling Hard Capsule Shells
***Check the book: coni-snap capsule parts, coni-snap and coni-snap
supro capsule sizes (as in actual size of capsule in relation to a quart)  Use punch method
 Steps:
Capsule Sizes  Count the capsules
 Powder encapsulated placed on a sheet of
000 15 grains 972mg (largest) clean paper or a glass or porcelain plate
00 10 grains 648mg  Powder mixed formed into a cake depth of
0 7.5 grains 486mg approximately ¼ to 1/3 the length of the
1 5 grains 324mg capsule body
2 4 grains 259mg  Empty capsule punched vertically into the
3 3 grains 194mg powder cake until filled
4 2 grains 130mg
5 1 grain 64.8mg (smallest) Process of Capsule Filling

 Milling or sieving of all ingredients

Preparation of Filled Hard Gelatin Capsules  Blending
 Powder blender or empty capsules
 Formulation development and preparation and selection of  Capsule filler
capsule size  Capsule deduster or cleaner
 Filling the capsule shells  Capsule injection screen
 Capsule sealing (optional)  Capsule check-weighing system or reject
 Cleaning and polishing of filled capsules  Finished capsules
 Packaging
Examples of Fill in Hard Gelatin Capsules
***Check book: profill system
 Powder or granulate
 Pellet mixture Capsule Sealing
 Paste
 Capsule  For the manufacturers:
 Tablet  Sealing the joint between the 2 capsule parts
using:
Developing the Formulation and Selection of Capsule Size  Colored band of gelatin (KAPSEALS,
Parker Davis)
 Goals in preparing a capsule:  Heat welding process
 Accurate dosage o Fuses the capsule cap to the
 Good availability body through the double wall
 Ease of filling and production thickness at their juncture
 Stability (distinctive “ring” around the
 Elegance capsule)
 Liquid wetting agent (liquid sealing-
Dry Formulations water and ethanol sprayed around the
seam area), followed by thermal
 Blended thoroughly (active and inactive components) to bonding
ensure uniformity of powder mix for the fill  Extemporaneously
o Warm gelatin solution,
Care in Blending lightly coating the inner
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 surface of the cap prior to  Polyethylene glycols and nonionic surface active
placement on the filled agents as polysorbate 80
capsule body  Water-miscible and relatively nonvolatile compounds
 Propylene glycol and isopropyl alcohol
Cleaning and Polishing Capsules (depending on factors as concentration used and
packaging conditions)
 Small scale
 By rubbing with a clean gauze or cloth
 Large scale Soft Medications Commercially Prepared into Soft Gelatin Capsules
 Cleaning vacuum affixed to the capsule-filling
machines (removes any extraneous material)  Acetazolamide: Diamox sequels: Carbonic anhydrase
using Accela-Cota apparatus inhibitor
 Cyclosporine: Sandimmune, Neoral: Immunosuppressive
Some Medications Commercially Prepared into Soft Gelatin  Ethosuximide: Zarontin: Anticonvulsant
Capsules  Ranitidine HCl: Zantac Geldose: Histamine H 2 receptor
inhibitor
 Acetazolamide: Diamox: Carbonic anhydrase inhibitor
 Cyclosporine: Sandimmune: Immunosuppressive
 Cyclosporine: Neoral: Immunosuppressive Liquids that cannot be Encapsulated into a Soft Gelatin Capsule
 Digoxin: Lanoxicaps: Cardiac glycoside
 Ethosuximide: Zarontin: Anticonvulsant  Easily migrate through capsule shell like materials with
 Ranitidine HCl: Zantac Geldose: Histamine H 2 receptor water above 5%
inhibitor  Low molecular weight
 Water soluble and water volatile organic compounds
(alcohols, ketones, acids, amine, and esters)
Preparation of Soft Gelatin Capsules

 Plate process Solids that may be Encapsulated into a Soft Gelatin Capsule
 Uses set of molds to form capsules
 Rotary die process  Solutions in a suitable liquid solvent, suspensions, dry
 Most commonly used powders, granules, pellets or small tablets
 Rotary die machine
 Liquid gelatin flowing from an overhead tank
into two continuous ribbons brought together Compendial Requirements for Capsules
between rotating die
 More efficient and productive  Added substances may only be used:
 Results in bicolored capsules  Harmless in the quantities used
 Very accurate filling (+/-1-3%)  Do not exceed the minimum amount required to
 Reciprocating die process provide their intended effect
 Norton capsule machine  Do not impair the product’s bioavailability
 Similar to rotary die (gelatin ribbons are formed) therapeutic efficacy or safety
 Differs in encapsulating process  Do not interfere with requisite compendial assays
 Produced, filled and sealed in a continuous and tests
operation
 Accogel capsule machine
 Stern Machine Comparison Between Hard and Soft Capsules
 Unlike the other fill dry powders into soft elastic
capsules Property Hard Capsule Soft Capsule
 Also use liquids or liquids and powders as fill
 Used to cover tablets with a gelatin film (geltabs) Shell  Made of  Gelatin,
 Variety of shapes, sizes, color possible gelatin, sugar plasticizer
and powder (glycerin) or
polyhydric
Utilization of Soft Gelatin Capsules alcohol
(sorbitol) water
 To contain a variety of liquid, pastry and dry fills and etc.,
colorants
Manufacturi  Shells  Shells and fill
Uses of Soft Gelatin Capsules ng processes produced made and
separately combined on
 Water-immiscible volatile and nonvolatile liquids from the fill one and the
 Vegetable and aromatic oils, aromatic and  Continuous same process
aliphatic hydrocarbons, chlorinated dipping, line
hydrocarbons, ethers, esters, alcohols and organic drying,  By: plate
acids removing and process, rotary
 Water-miscible nonvolatile liquids joining of die process and
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 capsules as peg reciprocating  Contents of a specified number of capsules can
containing die process be removed
plates rotate in  Empty capsule shells dissolved in the dissolution
and out of medium
gelatin bath  Weight variation
Content  Dry powders  Liquids and  Hard Capsules
or granules, semi-liquids,  Individual weight of 10 capsules – weight of
pellet mixture, suspensions, empty shells = net weight of performed
paste, small pasty assay for content of active ingredient
capsule and materials, dry according to monograph
tablets powders and  Soft capsules
preformed  Same as above, cut open the capsule and the
tablets content is removed by dissolving with
Formulation  13%-16%  More moisture suitable solvent
technology moisture  Water content  Content uniformity
content of fill not more  Amount of active ingredient (determined by assay)
 Moisture proof than 5% must be:
packaging  Addition of  Within 85% to 115%of the label claim for 9-
needed titanium 10 dosage units
 Encapsulation dioxides or  No unit outside the range of 70% to 125% of
using iron oxides for label claim
succinylated light sensitive  Additional test are needed when 2-3 dosage
gelatin shells units are outside of the desired range but
 Packed in within the stated extremes.
aluminum  Weight variation and content uniformity: uniformity
blisters of dosage units can be determined
 Encapsulation  Content labeling requirement
uses  Express the quantity of each active ingredient in per
succinylated, dosage unit
glycerol-free  Stability testing
shell  Factors like temperature, humidity, light, formulative
formulation, components and other container closure system using
addition of long term and accelerated stability tests
PVP to the fill  Moisture permeation test
 For single unit and unit-dose containers to assure
suitability for packaging
 Containers for dispensing capsules  Uses color revealing desiccant pellet for color change
 Tight and weight changes
 Well-closed
 Light-resistant
 In glass or plastic containers Examples of some official capsules: Table 7.2: memorize
 Some with packets of desiccant (prevents
absorption of excessive moisture) Inspection
 Unit dose and strip packaging of solid
dosage forms provides:  Visual or electric inspection
o Sanitary handling of the  To detect any flaws in the integrity and appearance of
medications the capsules
o Ease of identification  Defective caps should be rejected.
o Security in accountability for  CGMP regulations if number of production flaws is
medications excessive
 The cause must be investigated, documented and steps
 Disintegration test fop capsules
undertaken to correct the problem.
 Uses basket rack assembly, immersed 30 times per
Counting
minute into a thermostatically controlled fluid (37 oC)
and observed over the time described in the individual
 Community pharmacy
monograph
 Counting small numbers of solid dosage units:
 To satisfy the test, the capsules disintegrate
specifically designed trays are used
completely into a soft mass having no palpably firm
 Spatula used to count and sweep the dosage units into
core and only some fragments of the gelatin shell
the trough until the desired number is reached
 Dissolution test for capsules
 Tray must be wiped clean after every use to prevent
 USP Apparatus I (stainless steel basket on a stirrer
batch-to-batch contamination
shaft) and USP apparatus II ( using paddle as the
 Industrial scale
stirrer): same apparatus for immediate release tablet
 Use of automated pieces of equipment dosage units
 If the capsule shells interfere with the chemical
into bulk containers
analysis before proceeding with the sampling and
chemical analysis:

5
Packaging

 Caps are packaged in:

 Glass or in plastic containers
 Some containing packets of desiccant ( prevent
absorption of excessive moisture)
 Unit dose and strip packaging of solid dosage forms
 Provides sanitary handling of the medications
 Ease of identification
 Security in accountability for medication
Storage

 Caps should be stored in tightly capped containers in a

cool, dry place.