Transcript Solution dosage form

Solution dosage form
Lecture 3
Oral solutions
Dry mixtures for solution
- Certain antibiotics have insufficient stability in aqueous
solution to meet extended shelf life periods.
- They are provided in dry powders or granules for
reconstitution with a prescribed amount of purified water
immediately before dispensing to the patient.
- - Once reconstituted, the solution remain stable in the
refrigerator for the labeled period usually 7-14 days
depending on the preparation.
Examples: Penicillin V Potasium for oral solution, USP
Cloxacillin Sodium for oral solution, USP
Oral rehydration solutions
Are usually effective in treatment of diarrhea and mild volume depletion (5-10% of
body weight). These are available OTC
Oral colonic lavage solution
Used for preparation of the bowel for colonoscopy, administration of a clear liquid
diet for 24 to 48 hours preceding the procedure, administration of an oral
laxative such as magnesium citrate the night before, and a cleansing enema
administered 2 to 4 hours prior to the procedure.
Syrups
Sweet or other Viscid Aqueous Solutions
Syrups are concentrated solutions of sugar such as sucrose in water or
other aqueous liquid.
simple syrup: when water is used alone for making syrup.
medicated syrup: when the aqueous preparation contains some added
medicinal substance
flavored syrup: which contains aromatic or pleasantly flavored
substances and is intended to be used as a vehicle or flavor for
prescriptions. They are accepted by both adult and children and as it
contains no or little alcohol, they are vehicle of choice for children
preparations
Acacia Syrup can mask the disagreeable
taste of many drugs due to its colloidal
character. Raspberry Syrup is useful in masking
the taste of bitter drugs.
Syrups
Syrups are concentrated aqueous preparations of a sugar substitute with or without flavoring
agents and medicinal substances. Syrups containing flavoring agents but not medicinal
substances are called nonmedicated or flavored vehicles (syrups) such as cherry syrup,
orange syrup and Raspberry syrup. These syrups are intended to serve as pleasant-tasting
vehicles for medicinal substances.
Medicinal syrups are commercially prepared from the starting materials , that is
by combining each of the individual components of the syrup, such as sucrose,
purified water, flavoring agents, coloring agents, the therapeutic agent, and other
necessary and described ingredients. Naturally, medicated syrups are employed in
therapeutics for the value of the medicinal agent present in the syrup.
Components of syrups
The sugar, usually sucrose or sugar substitute used to provide sweetness and
viscosity.
Antimicrobial preservatives
Flavorants and colorants
Also, many syrups contain special solvents, solubilizing agents, thickeners or
stabilizer.
- Sucrose is the sugar most frequently employed in syrups it may be replaced by other sugars or
substances such as sorbitol, glycerin and propylene glycol.
- In some instances, all glycogenetic substances (materials converted to glucose in the body) are
replaced by nonglycogenetic substances such as methylcellulose or hydroxy ethylcellulose.
These two materials are not hydrolyzed and absorbed into the blood stream, and their use
results in excellent syruplike vehicle for medications intended for use by diabetic patients.
- - Most syrups contain a high proportion of sucrose, usually 60 to 80% not only because of the
desirable sweetness and viscosity of such solutions but also because of their inherent stability in
contrast to unstable character of dilute sucrose solutions. Additionally, the concentrated sugar
solution are quite resistant to microbial growth.
- Simple syrup Syrup, NF, is prepared by dissolving 85g of sucrose in enough purified water to
make 100 ml of syrup.
- The slight excess of water permits the syrup to remain physically stable in varying temperatures. If
the syrup were completely saturated with sucrose, in cool storage some sucrose might
crystallize from solution.
As formulated, the official syrup is both stable and resistant to crystallization and microbial growth.
• The amount of preservative required to protect a syrup against microbial growth
varies with the proportion of water available for growth
• Preservative commonly used in syrups : benzoic acid 0.1-0.2%, sodium
benzoate 0.1-0.2%, parabens (0.1%)
• To enhance the appeal of the syrup, a coloring agent that correlates with the
flavorant employed (green with mint, brown with chocolate).
• Most syrups are flavored with synthetic flavorants or with naturally occurring
materials, such as volatile oils (orange oil), vanilin
• Colorant to enhance the appeal of the syrup may be added
• Sucrose-based syrup may be substituted by a polyol, such as sorbitol solution
USP, 64%
• Examples of medicated syrup:
• Analgesic
• Anticholenergic
• Antiemetics
• Anticonvulsant
• Antihistamine
• Antiviral
• Antitussives
• Expectrorant
• Bronchodilators
• Fecal softener
Polyols (e.g. glycerin or sorbitol) may be added to
- retard crystallization of sucrose or
- increase the solubility of added ingredients.
Alcohol often is included as
- preservative
- solvent for volatile oils.
Syrups possess remarkable masking properties for bitter and
saline drugs.
It is important that the concentration of sucrose approaches
but not quite reach the saturation point, WHY?
 In dilute solutions sucrose provides an excellent nutrient for
molds, yeasts, and other microorganisms.
 In concentration of 65 % by weight or more the solution will
retard the growth of such microorganisms (WHY?).
 A saturated solution may lead to crystallization of a part of the
sucrose under conditions of changing temperature.
When heat is used in the preparation of syrups, there is almost
certain to be an inversion of a slight portion of the sucrose.
C12H22O11
Sucrose
heat & acid
2 C6H12O6
Invert sugar
(dextrose and levulose)
The speed of inversion is greatly increased by acids (why ?);
the hydrogen ion acts as a catalyst in this hydrolytic reaction.
Invert sugar
 is more readily fermentable than sucrose
 tend to darken in color
 retard the oxidation of other substances.
The levulose formed during inversion is sweeter than sucrose;
therefore the resulting syrup is sweeter than the original syrup.
When syrup is overheated it caramelizes.
Invert Syrup:
 It is prepared by hydrolyzing sucrose with hydrochloric acid
and neutralizing the solution with Ca or Na carbonate.
 The sucrose in the 66.7% w/w solution must be at least 95%
inverted.
 The invert syrup, when mixed in suitable proportions with
syrup, prevents the deposition of crystals of sucrose under
most conditions of storage.
Invert Syrup:
 It is prepared by hydrolyzing sucrose with hydrochloric acid
and neutralizing the solution with Ca or Na carbonate.
 The sucrose in the 66.7% w/w solution must be at least 95%
inverted.
 The invert syrup, when mixed in suitable proportions with
syrup, prevents the deposition of crystals of sucrose under
most conditions of storage.
Preparation of Simple Syrup
(a) Solution with heat
This is the usual method of making syrups:
 in the absence of volatile agents or those injured by heat
 when it is desirable to make the syrup rapidly.
The sucrose is added to the purified water or aqueous solution
and heated until dissolved, then strained and sufficient purified
water added to make the desired weight or volume.
Excessive heating in the preparation of syrups must be
avoided to prevent inversion of sucrose, with increased
tendency to fermentation. Syrups cannot be sterilized by
autoclaving without caramelization (yellow color).
The specific gravity of syrup is an important property to
identify its concentration. Syrup has a specific gravity of about
1.313, which means that each 100 ml of syrup weighs 1313 g.
(b) Agitation without Heat
 This process is used in those cases where heat would cause
loss of valuable volatile constituents.
 The syrup is prepared by adding sucrose to the aqueous
solution in a bottle of about twice the size required for the
syrup. This permits active agitation and rapid solution.
 The stoppering of the bottle is important, as it prevents
contamination and loss during the process.
(c) Percolation
 In this procedure, purified water or an aqueous solution is
permitted to pass slowly through a bed of crystalline
sucrose, thus dissolving it and forming a syrup a pledget of
cotton is placed in the neck of the percolator
 If necessary, a portion of the liquid is repassed through the
percolator to dissolve all of the sucrose.
This method is used for the preparation of Syrup USP.
Preservation of Syrups
 The USP suggests that syrups be kept at a temperature not
above 25°C.
 Preservatives such as glycerin, methyl paraben, benzoic acid
and sodium benzoate may be added to prevent bacterial and
mold growth, particularly when the concentration of sucrose in
the syrup is low.
 The concentration of preservative is proportional to the free
water.
 The official syrups should be preserved in well dried bottles
and stored in a cool dark place.
Dextrose-Based Syrups
Dextrose may be used as a substitute for sucrose (WHEN?) in
syrups containing strong acids in order to eliminate the
discoloration associated with inversion.
Dextrose forms a saturated solution in water at 70% w/v,
which is less viscous than simple syrup.
It dissolves more slowly than sucrose and is less sweet
Preservatives are required to improve the keeping qualities of
such syrups. Glycerin is added in 30% to 45% v/v as
preservative.
Artificial Syrups (Non-Nutritive Syrups)
 intended as substitutes for syrups and are to be administered to
persons who must regulate their sugar and/or calorie intake
accurately. e.g. persons suffering from diabetes mellitus.
 Some early formulae included glycerin, however, glycerin and
propylene glycol are glycogenetic substances, i.e. they are
materials which are converted into glucose in the body.
 An example of non–nutritive syrup is “Diabetic Simple Syrup”. It
contains compound sodium cyclamate (6% cyclamate sodium
and 0.6% saccharin sodium)
However, the cyclamate studies showed that the sweetener could
produce cancer in animals and, as a result, this substance was
removed from a wide variety of products. Similar studies have been
carried out on saccharin. Much research has been done to find a safe
synthetic substitute for sucrose. As a result, aspartame which is about
200 times sweeter than sucrose, is being used now in many
commercial preparations as the sweetening agent.
Sorbitol-Based Syrups
Sorbitol which is hexahydric alcohol made by hydrogenation of
glucose has been used in the preparation of syrup.
It is used mostly in the form of a 70% w/w aqueous solution.
Sorbitol solution is not irritating to the membrane of the mouth
and throat and does not contribute to the formation of dental
carries.
Sorbitol is metabolized and converted to glucose; however, it is
not rapidly absorbed from the GlT as sugars. No significant
hyperglycemia has been found (WHY?); it may be used as
component of non-nutritive vehicles.
Sorbitol solution does not support mold growth. Preservative
should be used in solution containing less than 60% w/w
sorbitol.
It is chemically stable and inert with respect to drugs and other
ingredients used in pharmaceutical perpetration.
Mucilages
► The official mucillages are thick, viscid, adhesive liquids, produced by dispersing gum in
water or by extracting the mucilaginous principles from vegetable substances with water. The
mucillages decompose showing appreciable decrease in viscosity on storage. They should never
make in quantities larger than can be used immediately unless a preservative is added.
► Acacia Mucillage contains benzoic acid and tragacanth Mucillage contains alcohol and
chloroform water. Mucillage are used to aid in suspending insoluble substances in liquids. Their
colloidal character and viscosity help to prevent immediate sedimentation.
► The alcohol is used to disperse the gum to prevent agglomeration on addition of water.
Several synthetic mucilage-like substances such as polyvinyl alcohol, methylcellulose,
carboxymethylcellulose are used at the appropriate concentration as mucilage substitute,
emulsifying and suspending agents.
Jellies
► They are a class of gels contains water and having a jellylike consistency. Tragacanth
may be used with thickening agent. These preparations may be formulated with water from
acacia, gelatin, carboxymethylcellulose, hydroxyethylcellulose and similar substances. It has
many uses such as Ephedrine sulfate jelly, lubricant for gloves, topical preparations. Jellies are
prone to microbial contamination and contain preservatives such as methyl p-hydroxybenzoate.
Honeys
They are thick liquid used as a base. It is not much used nowadays.
Advantages
 If the drug is not completely soluble or unstable in aqueous
medium it may be necessary to use an alternative non-aqueous
solvent.
 Oily solutions of drugs are often used for depot therapy e.g. in
muscles
It is essential to test:
toxicity – irritancy – flammability – cost – stability and compatibility
of solvents to avoid problems
 Solvents such as acetone, benzene and petroleum ether are not
used for internal products.
 Internal products may contain ethanol, glycerol, propylene glycol
certain oils.
 For parental products the choice is very limited
This section is devoted to four groups of non-aqueous
solutions:
1. alcoholic or hydroalcoholic solutions, e.g. elixirs and spirits,
2. ethereal solutions, e.g. the collodions
3. glycerin solutions, e.g. the glycerites,
4. oleaginous soIutions e.g. the liniments, medicated oils, oleovitamins, sprays, and toothache drops.
ELIXIRS
 Are clear, pleasantly flavored, sweetened hydroalcoholic liquids
intended for oral use and usually flavored to enhance their palatability.
 They are used as flavors and vehicles e.g. Aromatic Elixir USP for
drug substances and when drug is added they are classified as
medicated elixirs. For example: Dexamethasone Elixir USP and
Phenobarbital Elixir USP are in use.
 The main ingredients in elixirs are ethanol and water but other
substance such as glycerin, sorbitol, propylene glycol, flavoring agents,
preservatives, and syrups are often used in the preparation of the final
product.
 EIixirs contain ethyl alcohol, however, the alcoholic content will vary
greatly, from elixir containing only a small quantity to those that
contain a considerable portion as a necessary aid to solubility
 An elixir may contain water and alcohol soluble ingredients.
Elixirs
Compared with syrups, elixirs are usually less sweet and less viscous
because they contain a lower proportion of sugar and consequently
are less effective than syrups in masking the taste of medicinal
substances.
Non-medicated elixirs are employed as vehicles.
In addition to alcohol and water, other solvents, such as glycerol and
propylene glycol are frequently employed in elixirs as adjunctive
solvents.
Because of their usual content of volatile oils and alcohol, elixirs should be stored in tight,
light-resistant containers and protected from excessive heat
Antihistamine Elixir: Diphenhydramine HCl
Analgesic Elixir: acetominophen
Cardiotonic Elixir: digoxin
Antispasmodic Elixir: hyoscyamine sulfate
Sedative Elixir: phenobarbital
Elixirs are sweetened with sucrose, sorbitol, glycerol, and/or artificial
sweeteners
Elixirs having a high alcoholic content usually use artificial sweetener
such as saccharin.
Most elixirs have coloring agents to enhance their appearance
Elixirs containing more than 10-12% alcohol are usually self-preserving.
The alcohol contents for elixirs vary greatly. For example Aromatic
Elixir USP contains 21 to 23% of alcohol; Compound Benzaldehyde
Elixir USP contains 3 to 5%. An elixir may contain both water and
alcohol soluble ingredients. Elixirs should be made brilliantly clear.
Incompatibilities:
Since elixirs contain alcohols, alcohol precipitates acacia and agar from aqueous
solutions. Similarly, it will precipitate many inorganic salts from solutions. If an
aqueous solution is added to an elixir a partial precipitation of alcohol-soluble
ingredient may occur due to the reduced alcoholic content of the final preparation. As
a vehicle for tinctures and fluidextracts, the elixirs generally cause a separation of
extractive matter from these products due to reduction of the alcoholic content.
Tinctures
In medicine, a tincture is an alcoholic extract (e.g.
•
of leaves or other plant material) or solution of a
non-volatile substance; e.g. of iodine,
mercurochrome).
Tinctures contain alcohol in amounts ranging from •
approx. 15-80%. The alcohol content protects
against microbial growth
Other solvent, such as glycerol, may be employed •
Tincture must be tightly stopered and not exposed •
to excessive temperature
Many tinctures must be stored in light-resistant
containers and protect from sunlight.

Some examples that were formerly common in 
:medicine include
Tincture of Cannabis sativa 
Tincture of Benzoin 
Tincture of cantharides 
Tincture of green soap (which contains also lavender)
Tincture of iodine
Tincture of opium (laudanum) 
(paregoric) Camphorated tincture of opium 
Tincture of iodine is often found in emergency survival
kits, used both to disinfect wounds and to sanitize
surface water for drinking.
When an alcohol solution is not desirable, Lugol's 
iodine, an aqueous solution of iodine in potassium
iodide solution, or povidone iodine (Betadine), a PVP
solution, can be used.
Other names for Lugol's solution are I2KI (Iodine- 
Potassium Iodide); Markodine, Strong solution
(Systemic); Aqueous Iodine Solution BP.

Topical tinctures

Iodine Tincture 
It is a reddish-brown colour tincture 
It is prepared from 2% iodine crystal and 2.4% sodium iodide in a vehicle 
alcohol/water (44-50% alcohol)
It is a popular local anti-infective agent applied to the skin in general household
first aid
Compound Benzoin tincture 
It is prepared from 10% benzoin and lesser amounts of aloe, storax and tolu 
balsam
The mixture is macerated in alcohol 
It is used to protect and toughen skin in the treatment of bedsores, ulcers, 
cracked nipples, and fissures of the anus
Also used in treatment of venereal warts 
It is also used as an inhalent for bronchitis and other respiratory conditions 
It is best stored in tight, light-resistant containers 

Thimerosal Tincture 
The vehicle is water, acetone and 50% alcohol 
It must be manufactured and stored in glass or suitably resistant 
containers
Ethylenediamine is used as stabilizer in the official solution and 
tincture
The commercial preparation is colored orange red, the colour 
defines the area of application
It is a commonly used household antiseptic for application to the 
skin abrasions and cuts and in preparation of patients for surgery
Green Soap tincture 
65% of active constituent in alcohol 
Also contains 2% lavender oil as perfume 
Used as detergent 