Pharmaceutics I

(PT303)
Lecture 4
 Syrups
• Clear, viscous, concentrated aqueous preparations of a sugar or sugar-substitute.
• Syrups serve as pleasant tasting vehicles to hide the bitter tasting APIs in
prescriptions especially for children.
Advantages of syrups:
1. Mask unpleasant taste of drugs due to: viscosity & sweetness.
2. Easy to swallow by children and elderly (compared to solid
dosage forms).
3. Can be given to pediatrics due to little or no alcohol content
(compared to elixir).
4. In cough & anti-tussive syrups, the thick and sweet syrup has
soothing effect on the irritated tissues of the throat.
5. Syrups prevent decomposition of herbal extracts.
due to  osmotic pressure of sucrose solution, inhibit the growth of
bacteria and molds, which cause decomposition of herbal extracts
 Disadvantages of syrups
1. Stability of the API is affected by the change
in syrup pH by the presence of flavoring
agents (acidic, neutral or basic).
2. If the syrup is completely saturated with
sucrose and stored in a cool place, some
sucrose might crystallize from solution,
causing the solution to be suitable for
microbial growth.
Syrups are stable against MO growth …. WHY? Because the amount of free water
is little, so no MO can grow, but when the syrup crystallizes, the free water
increases and now MO can grow.
 Components of syrup
1. sugars (sucrose/sugar-substitute) to provide sweetness and viscosity
2. preservative
3. flavoring agent
4. coloring agent
5. purified water
6. may contain solubilizing agents, thickeners and stabilizers
7. may contain polyols, such as glycerol or sorbitol …… WHY? retard
crystallization of sucrose or to increase the solubility of added
ingredients.
8. alcohol can act as both a preservative and a solvent for flavorants
1. Sugars (Sucrose and non-sucrose syrups)
➢ Sucrose is the most frequently used sugar in syrups
(sucrose-based syrups).
➢ Dextrose, sorbitol, glycerol and propylene glycol (non-
sucrose-based syrup) can also be used.
➢ In case of diabetic patients/diet controlled, all glycogenetic
substances (converted to glucose in the body) are replaced
by non-glycogenetic substances such as methylcellulose or
hydroxy ethylcellulose…. WHY? they are not hydrolyzed
and not absorbed into the blood stream.
➢ Sucrose has a disadvantage of causing dental caries.
➢ Sucrose syrups are sweet and viscous.
 1. Sugars (Sucrose substitutes)
A- Dextrose (D-glucose):
➢ Used in syrup containing an ACID to avoid the
inversion and brown discoloration (caramelization)
when using sucrose.
➢ Contains 70% w/v dextrose.
➢ Dextrose syrup is less viscous and less sweet than
sucrose syrup.
➢ Glycerin is used as preservative.
 reduction
1. Sugars (Sucrose substitutes)
B- Sorbitol:
➢ Hexahydric alcohol made by hydrogenation of glucose.
➢ Used in conc of 70% w/w in water.

Sorbitol advantages over sucrose:

➢ Not cause dental caries
➢ It is glycogenic (like sucrose i.e converted into glucose in the
body), however it is not absorbed rapidly, so not cause
hyperglycemia.
➢ Not support mold growth (alcoholic, self-preserved)
➢ Chemically stable & not affected by heat
 Simple syrup
BP 66.7% w/w USP 85% w/v
• Simple syrup contains a high proportion of sucrose (66-85%) to impart
desirable sweetness and viscosity and causes inherent stability (resistant
to crystallization and microbial growth).
• Dilute syrups are unstable and will be a nutrient medium for the growth of
microorganisms especially yeasts and molds.
• It requires no additional preservation if it is used immediately,
preservatives are only added if the syrup is to be stored and used later.
• Syrup USP is 85% w/v sucrose solution has a specific gravity of 1.313.
Why concentration of syrup approaches but not reaches saturation point
(nearly saturated solution)?
Why sucrose should be in the range of 66-85% in syrup?

If diluted (<66%) If saturated (>85%)

Microorganisms MO grow (Due to Crystallization of sucrose occurs upon cooling →
availability of the free water required separation of an amount of sucrose so the
for the growth of microorganisms) amount in solution becomes less than its
solubility at the storage temperature →
syrup would then be very diluted → suitable
for microbial growth
Explain how: "Official syrup is self-preserved" ?
Let's calculate free water:
85% w/v syrup is nearly saturated
It has a specific gravity of 1.313 (density= 1.313 g.ml)
Thus the mass of the 100 ml of syrup is 100*1.313= 131.3 g
The mass of water is 131.3- 85 (mass of sucrose)=46.3 g
To dissolve 1g of sucrose, you need 0.5 g water.
Hence 85 g of sucrose need 42.5 g
The remaining free water ( not engaged in sucrose solvation) =
46.3- 42.5= 3.8 ml
This volume is too low to support microbial growth
 Components of syrup
If syrup is freshly prepared and used, no preservatives are needed
2- Preservatives
- The amount of a preservative required to protect the syrup against
microbial growth varies with:
1. The amount of free water available for MO growth
2. The nature and preservative activity of some additives such as flavoring oil .
3. The capability of the preservative itself (spectrum of activity).
- Preservatives used are benzoic acid (0.1-0.2%), sodium benzoate (0.1-0.2%)
and various combinations of methyl, propyl and butyl parabens (0.1%).
- Alcohol is used in syrups to:
- assist dissolving of alcohol-soluble ingredients (flavorants, preservatives)
- has a preservative effect when its concentration reaches 15-20%
Methods of preparation of syrups

1. Solution by heat
2. Solution by agitation When to use?
3. Percolation of sucrose
1. Solution by heat: it is rapid method but NOT used for:
• Volatile substance (flavored substances)
• Substance affected by heat (thermolabile)
The sucrose is added to the purified water or aqueous solution and heated just
until dissolved, then strained and sufficient purified water added to make the
desired weight or volume.

Avoid excessive heating during the preparation of syrup ….

WHY? to prevent inversion of sucrose

Sucrose (di) + Heat dextrose + levulose (monosaccharides)

formed.
 Invert sugar (levulose) properties:
➢ More fermentable
➢ Tend to darken in color (discoloration)
➢ Overheating causes carmelization (brown color)
➢ Protects API from oxidation (levulose is a reducing sugar)
➢ Levulose formed is sweeter than sucrose
Sweetness in taste
Advantages of levulose syrup:
1- Prevent oxidation of APIs Dextrose Sucrose Levulose
2- Sweeter taste
Acacia Syrup is prepared by solution with heat and used as flavored vehicle
2. Solution by agitation:
➢To avoid heat-induced inversion of sucrose
➢Suitable for volatile and thermolabile substances
➢Sucrose + water in bottle of twice size (allow space for agitation)→
shake till dissolve
➢Used for codeine phosphate syrup (cough syrup)

API
Sucrose
Dist. water
3. Percolation of sucrose:
➢ A piece of cotton is placed in the neck
Sucrose

of the percolator to prevent the

passage of undissolved sucrose.

➢ Coarse crystalline sucrose must be

used to avoid formation of compact
mass & the liquid can not pass
Syrup
through it.

Simple syrup USP is an example of syrup prepared by percolation

 Artificial syrup (Non-nutritive syrup)
used for: 1- Diabetic patient
2- People regulating their diet

Composition:
1. Sodium carboxymethyl cellulose (↑viscosity).
2. Artificial sweeteners (stevia, aspartame, tagatose & xylitol).
 Other sweet & viscous preparations
Mucilage:
➢ They are viscous, adhesive liquids of polysaccharides, produced by
dispersing gum in water.
➢ They can be natural (acacia) or synthetic (carboxymethyl cellulose).
➢ Mucilages are used as suspending agents in suspensions.
➢ Preservatives must be added to the mucilage to prevent its
deterioration.
water
 Tinctures
- They are prepared by soaking the APIs from natural or chemical origin in
an alcoholic or hydroalcoholic solutions.

- They contain alcohol in the range of 15-80%, therefore they must be

stored in air-tight containers and in a cool place.
Examples of pharmaceutical topical tinctures
Coal tar topical solution: alcoholic solution containing 20% coal
tar. It is a local preparation used to treat skin disorders as
eczema.
Iodine tincture: alcoholic solution containing 2-7% iodine, has
antiseptic effect. ‫صبغة يود‬
Differs from tincture Spirits
More concentrated
Must be diluted - Alcoholic or hydroalcoholic solutions of volatile
substances. They contain high alcohol content (over
60%), so they have greater solubility for aromatic or
volatile substances than aromatic waters.
- They are pharmaceutically used as flavoring agents
(spirit of lemon, mentha) and medicinally used for the
therapeutic effect of the aromatic substance.
- They may be taken orally (mixed with water to reduce
pungency of the spirit), applied externally or used by
inhalation.
- Take care: When mixed with water, the volatile
substances in spirits may separate from the solution
and form a milky preparation (cautious dilution).
 Liniments
➢ Liniments are alcoholic (rubefacient / counterirritant / penetrating action) or
oleaginous solutions (massage) or emulsions of various medicinal substances
intended to be rubbed on the skin, NOT applied to broken or bruised skin to
avoid excessive irritation. The vehicle (alcoholic – oleaginous – emulsion) is
chosen based on the action and the solubility of the components.

➢ Oils in oleaginous liniments can be fixed (sesame /

cottonseed) oils or volatile (wintergreen / turpentine) oils.
➢Oleaginous liniments are less irritant than
alcoholic liniments.
➢All liniments should have a label “For External
Use” and emulsion liniments should have
extra label “Shake Before Use” and stored in
tight containers.
 Collodions
▪ They are liquid preparations composed of pyroxylin dissolved in a solvent mixture
(alcohol & ether). It forms a precipitate upon adding water.
▪ Pyroxylin is obtained by mixing nitric & sulfuric acids with cotton (cellulose). It has
the appearance of raw cotton when dry, but has harsh texture. They must be
labeled “For External Use”.
 Collodions
• Collodions are flammable so must be
stored in well-closed containers (solvent
is volatile) protected from light and away
from flames (temperature must be less
than 30°C).
• Collodions are intended for external use, applied to
dry skin with a fine brush or glass applicator, in
which the solvent rapidly evaporates leaving a thin
filmy residue of pyroxylin (occlusive protective
coating), if medicated it firmly places the drug on
the skin.
 Collodions
❑The collodion film is useful in holding the edges of incised
wound together, but its presence on the skin is uncomfortable
because it is inflexible. How to add flexibility to collodion?
Flexible collodion: is prepared by adding 2% camphor
(makes product waterproof) + 3% castor oil (causing
the product to be flexible and comfortable use on
moving skin areas as fingers, toes, joints). It is applied
by physicians over bandages or stitched skin incisions
to make them waterproof and protect them from
external stress.
Salicylic acid collodion: is 10% solution in flexible
collodion. It is keratolytic used for removal of warts
from the fingers & toes.
Famous aqueous
external solutions
 1- Mouthwashes

Mouthwashes are hydroalcoholic solution, can be used for therapeutic

& cosmetic purposes
(I) Therapeutic mouthwashes: to treat gingivitis, dental caries, stomatitis.
➢ Treatment of stomatitis, a painful side effect of cancer therapy (a
combination of hydrocortisone, nystatin and tetracycline)
➢ Prevention of gum bleeding after oral surgery (tranexamic acid)
➢ Anti-infective agent (chlorhexidine)
(II) Cosmetic mouthwashes: to clean and refresh the buccal cavity
(antimicrobial and/or flavoring agents)

Mouthwash may be diluted with water prior use

Mouthwashes generally contain five groups of excipients
1) Flavors: (menthol or methyl salicylate) to mask API disagreeable taste.
2) Humectants: (glycerin - sorbitol)
• increase the viscosity of the preparation
• enhance the sweetness of the product
• improve the preservative qualities of the product
3) Surfactants: aid in the solubilization of flavors and in the removal of food
debris by providing foaming action.
4) Alcohols:
• preservative
• solubilizing agent for APIs & flavoring agents
5) CoIoring agents: (amaranth)
 2- Gargles
Gargles are aqueous solutions used to treat the pharynx (throat) infections
(soreness in mild throat infections) by forcing air from the lungs through the
gargle, which is held in the throat; subsequently, the gargle is expectorated.

- Frequently containing antiseptics, antibiotics and/or anesthetics for

antiseptic, astringent and soothing effects
- Gargles may be diluted with water prior use.
- Phenol Gargle, Betadine Gargle contains phenol, glycerin, amaranth
solution in water.
 3- Enemas
An enema is an injected liquid into the rectum via the anus to either
administer medication
- They are(coma patients,
rectal injection pediatrics)
that are orrectum,
introduced into flush types:
out colon
contents.
(I) Evacuation enemas used to evacuate stool in constipation or
before surgery. They act by stimulating peristalsis (soap enema is
composed of 5% soft soap, marketed as single-dose disposable
unit).
(II) Therapeutic (retention) enemas:may contain medicaments
required to exert a local effect in the large bowel (anthelmintic
enemas or sulphamerazine rectal enema for the treatment of
ulcerative colitis).
(III) Diagnostic enemas They contain radio-opaque substances for
X- ray diagnostic investigation in the large bowel (barium sulfate
enema is composed of barium sulfate, acacia mucilage and starch).
 4- Douches
Douche is an aqueous solution, directed into a body cavity by using bulb
syringe. It functions as a cleansing, antiseptic agent, astringent or promote
healing.
- Douches are most frequently dispensed in the form of:
(1) Powder with directions for dissolving in a specified quantity
of water (usually warm).
(2) Tablets for preparing solutions
If powders or tablets are supplied, they must be free from
insoluble material, in order to produce a clear solution.
(3) Solutions
 5- Nasal Solutions
Aqueous solutions administered to the nasal mucosa in
small volume in form of drops or sprays.

- Nasal solutions may have local effect to reduce nasal congestion and irritation
(ephedrine sulfate as decongestant) (chlorpheniramine maleate as
antihistaminic)for have systemic effect (insulin and other hormones which are
inactivated when administered orally).
- Nasal decongestant solutions as drops or sprays are employed in the
treatment of rhinitis in common cold and of allergic rhinitis (hay fever) and of
sinusitis..
- They are usually formulated to be isotonic with nasal secretions and buffered
as nasal secretions (pH of 5.5 - 6.5) in order to minimize damage of nasal cilia.
 6- Eye (Ophthalmic) Solutions
Eye drops are sterile and isotonic solutions containing drugs or only lubricating or
tears-replacing solution.
Excipients:
1. Permeation enhancers to increase of the permeation of the drug
through the ophthalmic barrier (polyoxyethylene glycol ester and
ethylenediamine tetra acetic acid sodium salt). (to overcome
short residence time of solution in eye)
2. Viscosity enhancers by increasing the viscosity of
solution allow the improvement of the residence time
on the eye and the local bioavailability of the drug
(hydroxy methylcellulose, hydroxy ethylcellulose).
3. Preservatives
 7- Otic (Aural) Solutions
They are solutions of medicaments designed to exert a local effect in the
ear, to soften wax, to treat local inflammation and infections, or to relieve
pain.

✓ Solvents used: glycerin, propylene glycol or water. The

viscous glycerin or propylene glycol permit the drug to
remain in the ear for a long time.
✓ Surfactants can be added to aid in the removal of
cerumen (ear wax).
✓ The main classes of drugs used include: local anesthetics
(benzocaine); antibiotics (neomycin); and anti-
inflammatory (cortisone).
 8- Topical Solutions Differ from Lugol
Povidone iodine alcoholic topical solution: solution (I2 / KI)
A chemical complex of iodine with polyvinylpyrrolidone (PVP). PVP is a polymer
having an average molecular weight of about 40,000. It contains 10% (PVP-I) and
slowly releases it when applied to the skin. The preparation is employed
topically as a surgical scrub and non-irritating antiseptic solution.

PVP-I alcoholic
solution
 Give the scientific name
Scientific
Sentence
term
1. They are liquid preparations
composed of pyroxylin dissolved
in a solvent mixture of ethanol
and ether.
2. They are alcoholic (rubefacient /
counter-irritant / penetrating
action) or oleaginous solutions
(massage) or emulsions of various
medicinal substances intended to
be rubbed on the skin.