Pharmaceutical

Solutions and Other

Liquid Dosage Forms

Pharmaceutical solutions:
are liquid preparations that contain one or more chemical
substances dissolved in a suitable solvent or mixture of
mutually miscible solvents.

Classification

1- According to its use as oral, otic, ophthalmic, or
topical,etc.
2- According to their composition , classified as ,
syrups are aqueous solutions containing a sugar.
elixirs are sweetened hydro alcoholic (combinations of
water and ethanol) solutions.
spirits are aromatic materials if the solvent is alcoholic.
aromatic waters if the solvent is aqueous.
Solutions prepared by extracting active constituents from
crude drugs are termed tinctures or Fluid extracts,
depending on their method of preparation and
concentration.

Tinctures may also be solutions of chemical substances
dissolved in alcohol or in a hydro alcoholic solvent.

Certain solutions prepared to be sterile and pyrogen
free and intended for parenteral administration are
classified as injections.

Advantages of solutions as an oral dosage form:

1. Liquids are easier to swallow, so they are preferred for
pediatric and geriatric use.

2. Drugs administered in the form of a solution are
immediately available for absorption.

3. Solutions are homogenous systems i.e the drug is
uniformly distributed throughout the preparation.

4. Irritation is reduced by administration of a solution of a
drug due to the immediate dilution by the gastric
contents.
Disadvantages of solutions as an oral dosage
form:

1. Liquids are bulky to transport and store.

2. Poor stability of ingredients in aqueous solutions.

3. Solutions often provide suitable media for the growth
of m.o. and may therefore require the incorporation of a
preservative.

4. The taste of a drug, is always more pronounced when
in solution. Solutions can, however, easily be sweetened
and flavored to make them more palatable.

5. Accurate dosage usually depends on the ability of the
patient to use a spoon or, a volumetric dropper.
Solutions can be classified according to the type of
solvent in which the active ingredients are
dissolved into:

A. Aqueous Solutions

B. Non- Aqueous Solutions.
A. Aqueous Solutions:

Water is the most widely used solvent for use as a vehicle
for pharmaceutical products due to:

1. Lack of toxicity.
2. Physiological compatibility.
3. Ability to dissolve a wide range of materials.

Naturally occurring water containing varying amounts of
dissolved inorganic salts, Na, K, ca, Mg and iron, Cl
-
,
SO
4
- -
and CO
3
- -
, along with dissolved and undissolved
organic matter and microorganisms.
Drinking water
must meet the regulations with respect to bacteriologic purity.
Acceptable drinking water should be

Clear,
Colorless
Odorless and
Neutral or only slightly acid or alkaline,

The deviation from neutral being due to the nature of the
dissolved solids and gases (carbon dioxide contributing to
the acidity and ammonia to the alkalinity of water).
Drinking tap water is unacceptable for the manufacture of
aqueous pharmaceutical preparations because of the
possible chemical incompatibilities between dissolved
solids and the medicinal agents being added.

Signs of such incompatibilities are
Precipitation
Discoloration
and occasionally effervescence.

Purified water, is used in preparation of aqueous dosage
forms except those for parenteral administration
(injections) which need highly pure, sterile and pyrogen
free water.

Purified water, is obtained by

A. Distillation.
B. Ion exchange.
C. Reverse osmosis.

It contains fewer solid impurities than ordinary drinking water
reaching only 1% as much dissolved solids as tap water.

A. Distillation Method:
Stills in various sizes and styles with capacities ranging from
about 0.5 to 100 gallons of distillate per hour are used.

The first portion of aqueous distillate (about the first 10-20%)
must be discarded, Why?

Since it contains many foreign volatile substances usually
found in drinking water.

Also, the last portion of water (about 10% of the original
volume of water) remaining in the distillation apparatus must
be discarded Why?

Distillation to dryness results in decomposition of the
remaining solid impurities to volatile substances that
contaminates the previously collected portion of distillate.
B. Ion Exchange Method:

Advantages over distillation is that

no heat is required,
simple equipment,
ease of operation
and minimal maintenance of the equipment.

The ion exchange equipment passes water through a
column of cation and anion exchangers consisting of
water insoluble synthetic polymerized resins of high
molecular weight.


The resins are mainly of two types:

a. The cation, or acid exchangers, which permit
the exchange of the cations in water with
hydrogen ion-from the resin.

b. The anion, or base exchangers, which permit
the removal of anions from water.

These two processes are successively employed
to remove both cations and anions from water.


The processes are indicated as follows:
With M
+
indicating the metal cation ( as Na
+
)
and the X

indicating the anion (as cl

-
).

Cation exchange:
Hresin + M+ + X- + H2O M-resin + H+ + X- + H2O
(Pure)
Anion exchange:
Resin-NH2 + H+ + X- + H2O Resin-NH2 + HX + H2O
(Pure)
Water purified is referred to as demineralized or deionized
water.
C. Reverse Osmosis:

A pressurized stream of water is passed parallel to the inner
side of a filter membrane core.

A portion of the feed water, permeates the membrane as
filtrate, while the rest of water exits the system without being
filtered.

The filtered portion is called the "permeate" because it has
permeated the membrane.

The water that has passed through the system is called the
"concentrate" because it contains the concentrated
contaminants rejected by the membrane.

What is the difference between osmosis and
reverse osmosis?

In osmosis, the flow through a semipermeable
membrane is from a less concentrated solution to a more
concentrated solution, while in reverse osmosis, the flow
is from the more concentrated to the less concentrated
solution, thus the term reverse osmosis.



Approaches to the improvement of aqueous
solubility:
Complete solution of all ingredients in water is
sometimes difficult.

It is important that the concentration of any material
does not come close to its limit of solubility to prevent
precipitation if the product is cooled or if any evaporation
of the vehicle take place.

In these cases one or more of the following methods
may be used in order to improve aqueous solubility.
1. Cosolvency:

The solubility of a weak electrolyte or non-polar
compound in water by the addition of a water-
miscible solvent in which the compound is also
soluble.

Vehicles used in combination to increase the
solubility are called "co solvents".

The choice of suitable cosolvents is limited
because of possible toxicity and irritancy,
particularly for oral or parenteral use.



Suitable blends should possess values of dielectric
constant between 25 and 80.

e.g.a water / ethanol blend, other suitable solvents
including sorbitol, glycerol, propylene glycol and syrup.

A blend of propylene glycol and water is used to improve
the solubility of co-trimoxazole,

paracetamol is formulated as an elixir by the use of
alcohol, propylene glycol and syrup.

2. pH control:

The solubility of a weak base can be by the
pH of its solution whereas solubility of a weak acid
is by a pH .

The chosen pH must not conflict with other
product requirements.

The pH of optimum solubility Mostly is not the pH
of optimum stability.

The pH of parenteral and ophthalmic solutions,
must be controlled as extremes application to
mucous membranes can cause pain and irritation.
specially subcutaneous and intramuscular injections.

pH changes may affect :

The bioavailability of drugs
and the preservative activity by altering the
degrees of its ionization.

Maximum solubility may best be achieved by a balance
between pH control and concentration of cosolvent.

The inclusion of cosolvents such as alcohol or propylene
glycol will the dielectric constant of the vehicle and
the solubility of unionized form of the drug.

This of the polarity of the solvent system will also the
degree of dissociation of the drug and hence its pka will
be .

This will the concentration of the unionized (less soluble)
species, i.e. an in the pH of the system is necessary to
maintain solubility.


3. Solubilization:
The solubility of a drug in water can be improved by the
addition of a surface active agent.

This phenomenon is micellar solubilization.

A large excess of surfactant is undesirable because of
Cost
Possible toxic effects
Its effect on products aeration during manufacture.
It may also reduce the bioavailability of a drug due to its
strong adsorption within the micelle,

An insufficient amount of surfactants,may not solubilize all
of the drug or may lead to precipitation on storage or on
dilution of the product.
Hydrophilic surfactants with HLB values above 15 will be of
particular value as solubilizing agents.

The material chosen must be:

Non-toxic and non-irritant bearing in mind its
intended route of administration.

It must also be miscible with the solvent system,

Compatible with other ingredients,

Free from disagreeable odor and taste

and non-volatile.
Examples
The solubilization of fat-soluble vitamins using
polysorbates, enabling their inclusion with water-
soluble vitamins in the same formulation.

The solubilization of iodine to produce iodophores
is achieved by the use of macrogol ethers,
The advantages over simple iodine solutions
are:
Improved chemical stability,
Reduced loss of active agent due to sublimation,
Less corrosion of surgical instruments
and in some cases, enhanced activity.

The solubility of phenolic compounds such as cresol and
chloroxylenol which are soluble in water up to 2% and
0.03% respectively can be by solubilization with soaps

e.g. Lysol contains 50% cresol in an aqueous system by
the use of potassium soaps of oleic , linoleic and
linolenic acids.

It may be also possible to combine solubilization and
cosolvency in one formulation.

A 5% chloroxylenol solution can be formulated by the
inclusion of potassium ricinoleate, as well as ethanol and
terpineol as cosolvents.

Glycerol has also been used with polysorbate 80 to
improve the solubility of vitamin A.

4. Complexation:
Is to interact a poorly soluble drug with a soluble material
to form a soluble intermolecular complex.

most complexes are macromolecular

they tend to be inactive, being unable to cross lipid
membranes. therefore, complex formation should be
easily reversible so that the free drug is released during
or before contact with biological fluids.

The term "hydrotropy", which has been defined as the
increase in aqueous solubility of a material by the
inclusion of additives.

Many complexes are not water-soluble and may, in fact,
be better suited for the prolonged release of the drug.

E.g. the complexation of iodine with 10-15 % solution of
polyvinylpyrrolidone to improve the aqueous solubility of
the active agent.

The interaction of salicylates or benzoates with
xanthines such as theophylline or caffeine for.

5. Chemical modification:
Chemical modification of a drug in order to produce a
water soluble derivative.

Examples
The synthesis of the sodium phosphate salts of
hydrocortisone, prednisolone and betamethasone.

The water soluble chloramphenicol sodium succinate
has no antibacterial activity but is suitable for parenteral
administration as a solution to obtain high blood levels
after which it is converted back to the active base.
6. Particle size control:
The size and shape of very small particles, if
less than 1m diameter, can affect their
solubility.

As particle size decreases, solubility will
increase.
(B) Non-Aqueous Solutions:
To ensure complete solution of the ingredients at all
storage temperatures if the drug is unstable in aqueous
systems, by using an alternative solvent.

The advantages.
using the intramuscular injection of solutions of drugs in
oils as depot therapy.

Choosing a suitable solvent :
Its toxicity, Irritancy
Sensitizing potential Flammability,
Cost, Stability
Compatibility with other excipients
Non-aqueous solvents in pharmaceutical
preparations can be classified as:
non-volatile oils which consist mainly of fatty acid esters of
glycerol.
example, Almond oil which consists of glycerides mainly of
oleic acid, used as a solvent for oily phenol injection BP,

water being unsuitable Why?
because of the caustic nature of aqueous phenol solutions,

Olive oil, sesame oil, maize oil, cotton seed oil, Soya oil
and castor oil, are all suitable for parenteral use.

(I) Fixed oils of vegetable origin:

Some fixed oils are tasteless and a dourless to be
suitable for oral use as solvents for such materials as
vitamins (A) and (D).

Fractionated coconut oil is used as the solvent for
phenoxymethyl penicillin which would otherwise
hydrolyse rapidly if present in an aqueous system.

Oils tend to be unpleasant to use externally, unless
presented as an emulsion. Arachis oil is one of the few
examples and is used as the solvent in Methyl Salicylate
liniment B.P.

(II) Alcohols
It is used as primary solvent for many organic compounds.

Together with water, it forms a hydroalcoholic mixture that
dissolves both alcohol-soluble and water- soluble
substances, a feature useful in the extraction of active
constituents from crude drugs.

Alcohol is a solvent and excipient because of its miscibility
with water and its ability to dissolve many water- insoluble
ingredients, including drug substances, flavorants and
antimicrobial preservatives.

It is used as an antimicrobial preservative alone or with
parabens, benzoates, and other agents.


For the undesired pharmacologic and toxic effects of
alcohol when ingested by children. The (FDA)
recommended alcohol content limit of 0.5% for OTC oral
products for children under 6 years of age, 5 % for
children 6 to 12 years of age and 10% for children over
12 years of age.
.
The strength of diluted alcohol prepared by mixing equal
volumes of alcohol and purified water is not exactly half
that of the more concentrated alcohol but slightly greater.
Why?

The final volume of mixture is not the sum of the individual
volumes of the two components but about 3 % less than
what expected as liquids contract upon mixing.
Rubbing alcohol contains about 70% ethyl alcohol by
volume.

The remainder consisting of water, denaturants, with or
without color additives, perfume oils and stabilizers.

The use of this denaturant mixture makes the separation
of ethyl alcohol virtually impossible with ordinary
distillation apparatus.

This denaturant mixture is composed of 8 parts by
volume of acetone, 1.5 parts by volume of methyl
isobutylketone, and 100 parts by volume of ethyl alcohol.

The product is volatile and flammable and should be
stored in tight containers.


It is employed as:
1- Rubefacient and soothing externally,
2- Germicide for instruments
3- Skin cleanser prior to injection.
4- Vehicle for topical preparations

Isopropyl rubbing alcohol is about 70% by volume
isopropyl alcohol,
The remainder consisting of water with or without color
additives, stabilizers and perfume oils.
It is used externally as a:
1- Rubefacient and soothing rub
2- Vehicle for topical products.


(III) Polyhydric alcohols:
Alcohols containing two hydroxyl groups per molecule
are known as glycols but due to their toxicity are rarely
used internally.

One important exception is propylene glycol which is
used in conjunction with water or glycerol as cosolvent.

CH3.CH (OH)-CH2-OH
The lower molecular weight polyethylene glycols (PEG)
or macrogols can be used as cosolvents with alcohol or
water but their main use is in the formulation of water-
miscible ointment bases.
OH CH2 (CH2CH2O)nCH2OH
Glycerol
an alcohol possessing three hydroxyl groups per
molecule, is also widely used particularly as a
cosolvent with water for oral use.

Glycerin has preservative qualities, it can be
used externally at higher concentrations, for
example in phenol Ear Drops.


(IV) Dimethyl sulphoxide :
This is a highly polar compound and is thought to aid the
penetration of drugs through the skin.

(V) Ethyl ether:
This material is widely used for the extraction of crude
drugs. It is, however, used as a cosolvent with alcohol in
some collodions.

(VI) Liquid paraffin:
The oily nature makes it unpleasant to use externally,
although it is often used as a solvent for the topical
application of drugs in emulsion formulations.

Internally, it is indigestible and absorbed only to a limited
extent, it is an example of emollient cathartic when given
internally in the form of emulsion.
(VII) Miscellaneous solvents:
Isopropyl myristate and isopropyl palmitate are used as
solvents for external use in cosmetics as:
- Their low viscosity
- lack of greasiness make them pleasant to use.

Xylene is present in some ear drops to dissolve ear wax.

It may be possible to improve the solubility of a drug in a
particular vehicle by the addition of a cosolvent.

example
Nitrocellulose is poorly soluble in both alcohol and ether
but soluble in mixture of both.
The formulation of Digoxin injection is best achieved by
the inclusion of both ethyl alcohol and propylene glycol.
Formulation additives in solutions:
(I) Buffers

(II) Flavors and perfumes

(III) Colors

(IV) Preservatives
(I) Buffers:
when dissolved in a solvent, enables it to resist any
change in pH when an acid or an alkali is to be added.

The choice of suitable buffer depends on the pH and
buffering capacity required.

It must be compatible with other excipients and have low
toxicity.

Most pharmaceutically acceptable buffering systems are
based on carbonates, citrates, gluconates, lactates,
phosphates or tartarates. Borates can be used for
external application but not to mucous membranes or to
abraded skin.

As the pH of most body fluids is 7.4
products such as injections, eye drops and
nasal drops should be buffered at this value.

Many body fluids themselves, have a buffering
capacity
when formulating low volume intravenous
injections or eye drops a wider pH range can be
tolerated.

There must be a compromise between a pH
which is physiologically acceptable and a pH of
maximum stability and solubility and optimum
bioavailability.


Benzyl penicillin injection.

The optimum pH range for the stability of penicillin
solutions is 6-7.

Hydrolysis readily occurs in aqueous solutions with the
formation of inactive benzyl penicilloic acid

This is accompanied by in pH which further catalyses
hydrolysis leading to progressively acidity and more rapid
hydrolysis until the antibiotic has been destroyed.

Decomposition can be retarded by buffering the pH of the
solution to 6-7 with 45% W/V sodium citrate.


II) Flavors and perfumes:
Sweetening agents may not be sufficient to render
palatable a product. a flavouring agent can be included
specially in pediatric formulation.

Flavouring and perfuming agents are natural or
synthetic.

Natural products include fruit juices, aromatic oils
(peppermint and lemon oils), herbs and spices as
concentrated extracts, alcoholic or aqueous solutions,
syrups or spirits.
Artificial perfumes and flavours are synthetic,
They tend to be:

- Cheaper
- More readily available,
- Less variable in chemical composition
- More stable

They are usually available as alcoholic or
aqueous solutions or as powders.

Sometimes there is a strong association between the
use of a product and its flavour or perfume content.

example, products intended for the relief of indigestion are
often mint flavoured as mint has been used for its
carminative effect.

Other materials for the masking of unpleasant tastes
include menthol, peppermint oil and chloroform.

In addition to their own particular tastes and odours, they
also act as desensitizing agents by the exertion of a mild
anaesthetic effect on the sensory taste receptors.

Flavour- enhancing agents such as citric acid and glycine
or monosodium glutamate are widely used in solutions

(III) Colours:
It is useful to include a colour which is associated with
the used flavour to improve the attractiveness of the
product.

There is available range of both natural and synthetic
colours. The former, which tend to be more widely
acceptable than synthetic ones.

They exhibit problems namely variations in availability
and in chemical composition, both of which may cause
formulation difficulties.

Synthetic dyes tend to give brighter colours and are
generally more stable than natural materials.
(IV) Preservatives:
There are two strategies to be adopted in the
preparation of microbiologically acceptable
pharmaceutical preparations.

1- To minimize the access of microorganisms
from the sources.

2- To formulate the final product with inclusion of
preservatives.
Sources of contamination of solutions:
(1) Equipment:

- Should be simple for the purposes required
- With a minimum of junctions, valves and pumps, to allow
cleaning in place.

(2) Raw materials:

- Particularly those of natural origin, and water are a rich
source of microorganisms.
- Any treatment applied to remove or reduce the microbial
load must be such that the materials are not adversely
affected.
- A variety of processing procedures are available
including ionizing radiations, microwaves, gassing and
heat.
(3) Personnel:

To control contamination, of little importance unless the
personnel understand and appreciate the problems and
significance of microbial contamination.

Education in hygiene minimizes the introduction of
microorganisms by staff.

A full range of appropriate clothing must be available to
protect the product from body surfaces such as hood,
mask, overall protective gloves and boots.

preservatives
When choosing a suitable preservative, it must be
ensured that:

1- Adsorption on to the container from the product does not
occur or

2- Its efficiency is not impaired by the pH of the solution or
by interactions with other ingredients.

e.g.many of the widely used parahydroxybenzoic acid
esters are unable to exert their antimicrobial activity.
Why?
As they are adsorbed into the micelles of some non-ionic
surfactants.

Some examples of antimicrobial agents:
(1) Phenolics:

Distillation fractions of coal tar, include cresols, xylenols
and phenol.

all are toxic and caustic to skin and tissues.

Modification of the phenol molecule by the introduction
of cl
2
and cH
3
groups as in chlorocresol and
chloroxylenol has the dual effect of eliminating toxic and
corrosive properties and at the same time enhancing
and prolonging antimicrobial activity.

Thus, chlorocresol is used as bactericide in injections.
(2) Alcohols, acids and esters:
Ethyl alcohol, has long been used as preservative.

Aromatic substitution produce compounds which are less
volatile and less rapidly active.

e.g. phenylethanol for eye drops and contact lens
solutions,
benzyl alcohol in injections.

The organic acids, sorbic and benzoic and their esters,
because of their low toxicity, are well established as
preservatives.
We must be aware of chemical interactions
between the various components of a solution
that may alter the stability and/or potency.

Esters of p-hydroxybenzoic acid (methyl- ethyl-
propyl and butyl parabens), used in oral
preparations, have a tendency to partition into
certain flavoring oils.

This effect reduce the effective concentration of
the preservatives in the aqueous medium of the
product below the level needed for preservative
action.

(3) Quaternary ammonium compounds:
These cationic surface active compounds are derivatives of
an ammonium halide in which the hydrogen atoms are
substituted by at least one lipohilic group (Alkyl group).

They are mild in use and active at high dilutions as to be
non-toxic.

They are active as cations, alkaline conditions activity.

They interfere with cell permeability such that bacteria,
mainly the gram positive groups, leak their contents and
undergo lysis.

Gram negative bacteria are less susceptible.

Mixtures with other antimicrobial agents can be used.
(V) Reducing agents and antioxidants:

The decomposition of pharmaceutical products by
oxidation can be controlled by the addition of
reducing agents or antioxidants.
(VI) Sweetening agents:
MW carbohydrates particularly sucrose are the
most widely used sweetening agents.

Sucrose is colourless, very soluble in water,
stable over a pH range of about 4-8.

Polyhydric alcohols such as sorbitol, mannitol
and to a lesser extent glycerol can be included
in preparations for diabetic use.
Artificial sweeteners can be used both in
conjunction with sugars and alcohols to enhance
the degree of sweetness or on their own in
formulations for patients who must restrict their
sugar intake.

They are more sweeter than sucrose and therefore
rarely required at a concentration greater than
about 0.2%.

The most widely used is the sodium or calcium salt
of saccharin, exhibiting a high water solubility and
are chemically and physically stable over a wide pH
range.

(VII) Isotonicity modifiers :
Solutions for injection, for application to mucous
membranes and large volume solutions for
ophthalmic use must be made iso-osmotic with
tissue fluid to avoid pain and irritation.
preparation of solutions:

chemical agents in solvent require an extended time for
dissolving.

To hasten dissolution we may employ one of several
techniques:,
1-applying heat
2- reducing the particle size of the solute,
3- using a solubilizing agent,
4- or subjecting the ingredients to vigorous agitation.

Most chemical agents are more soluble at
temperatures because an endothermic reaction between
the solute and the solvent uses the energy of the heat to
enhance dissolution.

Many medicinal agents are destroyed at temperatures, and
the advantage of rapid solution may be completely offset by
drug deterioration.

If volatile solutes are used or if the solvent is volatile (as
alcohol), the heat the loss of these agents and must be
avoided.

Chemical agents, e.g. calcium salts, undergo exothermic
reactions as they dissolve and give off heat. the use of heat
discourages the formation of a solution.

E.g. calcium hydroxide, in the preparation of calcium
Hydroxide Topical Solution. It is soluble in water to the extent
of 140 mg per 100 ml at 25C, and 170 mg per 100 ml at
15C. the temperature of preparation or storage can affect
the concentration of the resultant solution.


In addition to or instead of the temperature of the
solvent to the rate of solution, we may the particle
size of the solute, by grinding the solid with a mortar and
pestle on a small scale or industrial micronizer on a large
scale, the particle size the surface area of the solute.

For and scale manufacture of solutions, the only
equipment suitable is mixing vessel, for agitation and a
filtration to ensure clarity of the solution.

Solutes present in concentrations, are often
predissolved in a small volume of the solvent and then
added to the bulk.

Volatile materials such as flavours and perfumes are
added at the end of the process and after cooling to
loss by evaporation.
Stability of solutions

Chemical and physical stability of solutions in their
containers is important. A solution must retain its initial
clarity, odour, colour, taste and viscosity over its shelf
life.

Clarity can easily be assessed by visual examination or
by a measurement of its optical density.

Colour assessed both visually and
spectrophotometrically.

The stability of flavours and perfumes must be also
assessed by chromatographic methods.
Types of solutions

Classified according to their route of administration into:


I) Oral Solutions:

Most oral solutions contain flavorants and colorants to
be more attractive and palatable.

They may also contain stabilizers to maintain the
chemical and physical stability of the medicinal agents
and preservatives to prevent the growth of
microorganisms in the solution.

In oral Liquid pharmaceuticals the patient receives the
usual dose of the medication in a conveniently
administered volume, as 5 ml (one teaspoonful), 10 ml,
or 15 ml (one tablespoonful).

Few solutions have large doses, e.g. magnesium citrate oral
solution, with a usual adult dose of 200 ml. On the other
hand, many solutions for children are given by drop with a
calibrated dropper.

Certain antibiotics, have insufficient stability in aqueous
solution to meet extended shelf life periods.

are provided in dry powder or granule form for
reconstitution with a prescribed amount of purified water
immediately before dispensing to the patient.

The dry powder mixture contains all of components, except
for the solvent.

Once reconstituted, the solution remains stable when stored
in the refrigerator for the labeled period, (7 to 14 days).

Syrups:
Concentrated aqueous preparations of a sugar or sugar
substitute with or without flavoring agent and medicinal
substances.

Syrups containing flavoring agents but not medicinal
substances are called non medicated or flavored syrups.

Syrups serve as pleasant tasting vehicles for medicinal
substances in the compounding of prescriptions.

Medicated syrups are commercially prepared, by
combining each of the individual component of the syrup,
e.g. antitussive and antihistamines.
Syrups are pleasant means of administration of a liquid
form of a disagreeable tasting drug.

They are effective in the administration of drugs to
youngsters.

Water soluble drug that is stable in aqueous solution
may be added to a flavored syrup.

Compatibility between the drug and the other
components of the syrup is a must.

Flavored syrups may have an acidic medium, or neutral
or slightly basic, the proper selection must be made
for the stability of any added medicinal agent.

Solid substances added directly to a syrup dissolve
slowly because

1- The viscous nature of the syrup does not permit the solid
substance to distribute readily throughout the syrup to
the available solvent.

2- The limited amount of available water in concentrated
syrups.

it is best to dissolve them in a minimal amount of
purified water and incorporate the resulting solution into
the syrup.

Components of Syrups
Contain the following components in addition to the
purified water and any medicinal agents.

A -The sugar, usually sucrose, or sugar substitute used to
provide sweetness and viscosity.

B - Antimicrobial preservatives.

C - Flavorants and colorants.

Syrups prepared commercially, contain special
solvents, solubilizing agents, thickeners, or stabilizers.
Sucrose and non-sucrose-based syrups:

Sucrose is used in syrups, it may be replaced by other
sugars and substances as sorbitol, glycerol and
propylene glycol.

Glycogenetic substances, are replaced by non
glycogenetic agents, such as methyl cellulose or
hydroxyl ethyl cellulose. Those are best used for patients
whose diet must be controlled (diabetic patients).

The viscosity resulting from their use is like that of
sucrose syrup.

Syrups contain usually 60 to 80%, not only because of
sweetness and viscosity, but also because of stability in
contrast to the dilute sucrose solutions.

Aqueous dilute sucrose solutions are good medium for
the growth of microorganisms, particularly yeast and
molds.

Conc sugar solutions are resistant to microbial growth
because of the unavailability of the water required for the
growth of microorganisms.

Simple syrup, prepared by dissolving 85 g sucrose in
purified water to make 100 ml of syrup.

Syrup has a specific gravity of about 1.313, which means
that 100 ml of syrup weighs 131.3 g

85 g of sucrose by difference, the weight of purified
water is about 46.3 g or ml which is used to dissolve 85
g of sucrose.



The solubility of sucrose in water is 1 g in 0.5 ml of
water

To dissolve 85 g of sucrose, about 42.5 ml of water
would be required.

i.e. very slight excess (about 3.8 ml of water per 100 ml of
syrup) which is not enough for the growth of
microorganisms.

Syrup requires no additional preservation if used soon,
preservatives are added only if the syrup is to be stored.


In cool storage, some sucrose crystallize from solution
acting as nuclei, it initiate a type of chain reaction that
would result in separation of an amount of sucrose.


The syrup would then be very much unsaturated
and probably suitable for microbial growth a
preservative is added.

The storage and use of syrups involves the
crystallization of the sugar within the screw cap
used to seal the containers.

This can be avoided by the addition of the
polyhydric alcohols (sorbitol- glycerol or
propylene glycol) or by the inclusion of invert
sugar which is a mixture of glucose and fructose.

Antimicrobial preservative:
The amount of effective preservative required varies with
the proportion of water available for growth of m.o.s.

Preservatives commonly used in syrups with effective
concentrations are:

-Benzoic acid 0.1-0.2 %, -Sodium benzoate 0.1-0.2%

-Combinations of methyl parabens, propyl parabens and
butyl parabens for about 0.1%.

-Alcohol in syrups assist in dissolving alcohol soluble
ingredients, but it is not present in amounts adequate for
preservation (15 to 20%).
Flavorant:
Syrups are flavored with synthetic flavorants or with
naturally occurring materials, such as volatile oils (e.g.
orange oil), to render the syrup pleasant tasting.

Because syrups are aqueous preparations, these
flavorants must be water soluble.

Sometimes a small amount of alcohol is added to syrup
to ensure the complete solution of a poorly water-soluble
flavorant.
Colorant:
To the appeal of the syrup, a coloring agent that
correlates with the flavorant employed (e.g. green with
mint, brown with chocolate) is used.

The colorant is generally:

- Water soluble

- Non reactive with other components and

- Color stable at the pH range and under the intensity of
light that syrup is likely exposed during its shelf life.
Preparation of syrups:
Syrups are mostly frequently prepared by one of four
general methods:

a. Solution with the aid of heat.

b. Solution by agitation without the aid of heat.

c. Addition of sucrose to a medicated or flavored liquid.

d. Percolation.
a. Solution with the aid of heat:
Applied to prepare the syrup as quickly as possible and if the
syrup's components are not damaged or volatilized by heat.

In this method:
1- The sugar is added to the purified water.

2- Heat is applied until the sugar is dissolved.

3- Other heat stable components are added to the hot syrup.

4- The mixture is allowed to cool, and its volume is adjusted to
the proper level by addition of purified water.

If heat labile agents or volatile substance such as volatile
flavoring oils and alcohol, are to be added, they are added to
the syrup after cooling to room temperature.
Overcome the use of excessive heat Why?

Sucrose, as a disaccharide, may be hydrolyzed into
monosaccharides, dextrose (glucose), and fructose
(levulose).

This hydrolytic reaction is inversion, and the combination of
the two monosaccharide products is invert sugar.

The speed of inversion is greatly increased by the presence
of acids, Why?

The hydrogen ion acts as a catalyst to the reaction.

The sweetness of the syrup is altered after
inversion, because invert sugar is sweeter than
sucrose, and the normally colorless syrup darkens
because the effect of heat on the levulose portion
of the invert sugar.

Because of the effect of decomposition by heat,
syrups con not be sterilized by autoclaving.

The use of purified water and the addition of
preservatives, protect the syrup during its shelf-life.
b. Solution by agitation without the aid of heat:
To avoid heat-induced inversion of sucrose, syrup may
be prepared without heat by agitation.

This process is more time consuming than use of heat,
but the product has maximum stability.
C. Addition of sucrose to a medicated or flavored
liquid:
A medicated liquid, such as tincture or fluid extract, is
employed as the source of medication in the preparation of
syrup.

Many tinctures and fluid extracts are prepared with
alcoholic or hydroalcoholic vehicles.

If the alcohol- soluble components are desired
medicaments, we render them water soluble.

If the alcohol- soluble components are unnecessary, they
are removed by:

1- mixing the tincture or fluid extract with water,
2-allowing the mixture to stand until the separation of
water-insoluble agents is complete,
3- Then filtering them from the mixture.

The filtrate is the medicated liquid to which the sucrose is
added.

If the tincture or fluid extract is miscible with aqueous
preparations, it may be added directly to simple syrup or
flavored syrup.
d. Percolation:
In this method, either
- sucrose may be percolated to prepare the syrup,

- or the source of the medicinal component may be
percolated to form an extractive to which sucrose or syrup
may be added.

Purified water or an aqueous solution is allowed to pass
slowly through a bed of crystalline sucrose, where a cotton
is placed in its neck, thus dissolving sucrose and forming a
syrup.
Linctuses:
It is a viscous preparation prescribed for the relief of
cough.

It consists of a simple solution of the active agent in a
high concentration of sucrose often with other
sweetening agents.

The syrup content has a demulcent action on the
mucous membranes of the throat.

For diabetic use, the sucrose is usually replaced by
sorbitol and/or synthetic sweeteners.
Elixirs:
They are clear, sweetened hydroalcoholic solutions
intended for oral use, usually flavored to enhance their
palatability.

Compared with syrups, they are less sweet and less
viscous because they contain a lower proportion of sugar
are less effective than syrups in masking the taste of
medicinal substances.

However, because of their hydroalcoholic character,
elixirs are better able than aqueous syrups to maintain
both water-soluble and alcohol-soluble components in
solution.
The proportion of alcohol in elixirs varies widely, according
to the water and alcohol solubility characteristics of the
individual components.

In addition to alcohol and water, other solvents, such as
glycerin and propylene glycol, are frequently employed in
elixirs as adjunctive solvents.

Although many elixirs are sweetened with sucrose or with
sucrose syrup, some use sorbitol, glycerin and/or artificial
sweeteners.

Elixirs with high alcoholic content usually use an artificial
sweetener, such as saccharin, only in small amounts rather
than sucrose, which only slightly soluble in alcohol and
requires greater quantities for equivalent sweetness.

Elixirs contain flavorings and coloring agents to increase
their palatability and enhance their appearance.

Elixirs containing more than 10 to 12% of alcohol are self-
preserving and do not require any antimicrobial agent.

A disadvantage of elixirs for children and for adults is their
alcoholic content.

Types of Elixirs:
Elixirs may be Non-medicated or medicated.

A) Non Medicated Elixirs:
Those elixirs may be useful to the pharmacist in the filling of
prescriptions involving:

a.The addition of a therapeutic agent to a pleasant tasting
vehicle.

b. Dilution of an existing medicated elixir.
In selecting a vehicle for a drug, the solubility and stability of
the drug in water and alcohol are concerned.

If a hydroalcoholic vehicle is selected, the proportion of
alcohol should be only slightly above the amount needed to
effect and maintain the drug's solution

When diluting a medicated elixir, the non medicated elixir
should have approximately the same alcoholic concentration
as the elixir being diluted.

Also, the flavor and color characteristics of the diluent
should not be in conflict with those of the medicated elixir,

All components should be chemically and physically
compatible. e.g. non medicated elixirs are: Aromatic elixir,
Compound benzaldehyde elixir, and Isoalcoholic elixir.
B) Medicated Elixirs:
Employed for the therapeutic benefit of the
medicinal agent.

Examples of medicated elixirs are:
Phenobarbital elixir used as sedative and
hypnotic, Acetaminophen elixir used as
analgesic, antipyretic and Diphenhydramine Hcl
elixir used as antihistaminic.


Preparation of Elixirs:
Prepared by simple solution with agitation and/ or by
admixture of two or more liquid ingredients.

Alcohol- soluble and water- soluble components are
generally dissolved separately in alcohol and in purified
water, respectively.

Then the aqueous solution is added to the alcoholic
solution, rather than the reverse, Why? to maintain the
highest possible alcoholic strength at all times so that
minimal separation the alcohol-soluble components
occurs.


When the two solutions are completely mixed, the final
mixture will be cloudy, because of separation of some of
the flavoring oils by the reduced alcoholic concentration.

If this occurs, the elixir is permitted to stand for a
number of hours to permit the oil globules to coalesce so
that they may be more easily removed by filtration.

Talc, is a frequent filter aid in the preparation of elixirs,
absorbs the excessive amounts of oils and therefore
assists in their removal from the solution.

The presence of glycerin, syrup, sorbitol and propylene
glycol in elixirs contributes to the solvent effect of the
hydroalcoholic vehicle, assists in the dissolution of the
solute, and enhances the stability of the preparation

Tinctures:
Alcoholic or hydroalcohlic solutions prepared from
vegetable materials or from chemical substances.

They vary in:
method of preparation,
strength of the active ingredient
alcoholic content.

When from chemical substances (e.g. iodine,
thiomerosal) tinctures are prepared by simple solution of
the chemical agent in the solvent.
They contain alcohol in amounts ranging from
approximately 15 to 80% according to the preparation.

The alcohol content protects against microbial growth
and keeps the alcohol soluble extractives in solution.

They must be tightly stoppered and not exposed to
excessive temperatures, Because of the alcoholic
content.

Tinctures undergo a photochemical change upon
exposure to light,must be stored in light- resistant
containers and protected from sunlight.

II) Topical solutions and tinctures:
Topical solutions employ an aqueous vehicle,
Topical tinctures employ an alcoholic vehicle.

They are prepared by
- simple dissolving - chemical reaction,
- maceration of the natural components in the
solvent as in compound benzoin tincture.
Because of the nature of the active ingredients or the
solvents, many topical solutions and tinctures are self-
preserved.

Those that are not may contain suitable preservatives.
Topical solutions and tinctures should be packaged in
containers that make them convenient to use.

Those that are used in small volume, such as the
anti-infectives, are usually packaged in glass or plastic
bottles with an applicator tip as a part of the cap or in
plastic squeeze bottles that deliver the medication in
drops.

Many of the anti-infective solutions and tinctures contain
a dye to delineate the area of application to the skin.

Lotions:
Can be formulated as solutions

Designed to be applied to the skin without
friction.

They may contain either humectants, so that
moisture is retained on the skin after application of
the product.

or alcohol which evaporates quickly, imparting a
cooling effect and leaving the skin dry.
Liniments:
Alcoholic or oleaginous solutions of various medicinal
substances to be rubbed on the skin.

Liniments with an alcoholic or hydroalcoholic vehicle are
useful when rubefacient, counterirritant or penetrating action
is desired,

Oleaginous liniments are employed primarily when massage
is desired. By their nature, oleaginous liniments are less
irritating to the skin than alcoholic liniments.

Liniments are not applied to skin areas that are broken
because excessive irritation might result. They can contain
such ingredients as methyl salicylate or camphor as counter-
irritants.
Collodions:
liquid preparations composed of pyroxylin (nitro
cellulose) in a solvent mixture usually composed
of alcohol and ether or alcohol and acetone
mixture with or without added medicinal agents.

They are for external use, when applied to the
skin with a fine hair brush, the solvent rapidly
evaporates, leaving a filmy residue of pyroxylin.
This provides an occlusive protective coating to
the skin, and when the collodion is medicated, it
leaves, a thin layer of that medication firmly
placed against the skin.

Its presence on the skin is uncomfortable
Why?

Because of its inflexible mature as its prepared by
dissolving pyroxylin (4% w/v) in a (3:1) mixture of
ether and alcohol and on application to the skin
and volatilization of the solvent, a protective film is
formed which is inflexible in nature.

Flexible collodion:
To render the product flexible, flexible collodion is prepared
by adding 2% camphor and 3% castor oil to collodion.

The castor oil renders the product flexible permitting its
comfortable use over skin areas that are normally moved,
such as fingers and toes.

The presence of camphor makes the product waterproof.

Example of flexible medicated collodion is "Salicylic acid
collodion" which consists of 10% solution of salicylic acid in
flexible collodion.

It is used for it keratolytic effects, especially in the removal of
corns from the toes.
III) Nasal Products:
Small volume solutions in an aqueous vehicle, oils being no
longer used for nasal administration.

Because the buffering capacity of nasal mucous is low,
formulation at a pH 6.8 is necessary.

Nasal drops should also be made isotonic with nasal
secretions using sodium chloride and

Viscosity can also be modified using cellulose derivatives if
necessary.

Active ingredients for administration by this route are usually
for local use and include antibiotics, anti-inflammatory and
decongestants.
IV) Sprays:
Aqueous or oleaginous solutions in the form of coarse droplets
or as finely divided solids to be applied topically, most usually
to the nasopharyngeal tract or to the skin.

Used as:

Intranasal to relieve nasal congestion and inflammation and
to combat infection and contain antihistamines,
sympathomimetic agents and antibiotic substances.

Against sunburn and heartburn contain local anesthetics,
antiseptics, skin protectants and antipruritics.
Throat sprays containing antiseptics, deodorants
and flavorant effective to relieve conditions such
as sore throat and laryngitis.

Other treat athlete's foot and fungal infections.

Numerous medicinal and cosmetic sprays are
available.

Several mechanical devices are commonly
employed.
The plastic spray bottle which gently squeezed to issue a
spray of its contents.

One way pump sprays with advantage of preventing
contamination for example nasal fluids after administration.

One type of atomizer with rubber bulb at the end of the
apparatus, when squeezed causes a flow of air, some of
which enters the glass reservoir and some of which exits
from the opposite end of the system.

The air forced into the reservoir causes the liquid to rise in a
small dip tube, forcing the solution up and into the stream of
air exiting the system. The air and the solution are forced
through a jet opening and the liquid is broken up into a
spray.

V) Ear drops:
They are simple solutions of drugs in either water,
glycerol, propylene glycol or alcohol / water
mixtures for local use and include antibiotics,
antiseptics, cleansing solutions and wax softeners.
VI) Vaginal and rectal solutions:
Vaginal Douches:

Prepared form powders (Douche powders) or from
liquid solutions or liquid concentrates.

Powders are used to prepare solutions for vaginal
douche, that is, for irrigation cleansing of the
vagina.

The powders themselves may be prepared and
packaged in bulk or as unit packages.

A unit package is designed to contain the amount of
powder to the specified volume of douche solution. The
powders are used by the teaspoonful or tablespoonful in
the preparation of solution.

Add the prescribed amount of powder to the appropriate
volume of warm water and stir until dissolved.

In liquid concentrates, it is instructed to add the
prescribed amount of concentrate (usually a teaspoonful
or cupful) to a certain amount of warm water.

The resultant solution contains the appropriate amount
of chemical agents in proper strength.


Among the components of vaginal douche powders are the
following:

1- Boric acid or sodium borate.

2- Astringents, e.g., potassium alum, ammonium alum, zinc
sulfate.

3- Antimicrobials, e.g., oxyquinoline sulfate, povidone iodine.

4- Quaternary ammonium compounds, e.g., benzethonium
chloride.

5- Detergents, e.g., sodium lauryl sulfate.

6- Oxidizing agents, e.g., sodium perborate.

7- Salts, e.g., sodium citrate, sodium chloride.

8- Aromatics, e.g., menthol, thymol, eucalyptol methyl
salicylate, phenol.

They are used for their hygienic effects. A few douche
powders containing specific therapeutic anti-infective
agents against monilial and trichomonal infections.

Enemas:
They are aqueous or oily solutions, as well as emulsions
and suspensions, are available for the rectal administration
of medicaments for cleansing, diagnostic or therapeutic
reasons.

Enemas are of two types:

1- Retention Enemas.

2- Evacuation Enemas.
1. Retention Enemas:
Solutions administered rectally for local effects (e.g.,
hydrocortisone) or for systemic absorption (e.g., aminophylline).

Aminophylline, rectal administration minimizes the
undesirable gastrointestinal reactions associated with oral
therapy.

Effective blood levels of the drug are usually obtained within
30 minutes followed rectal instillation.

Corticosteroids are administered as adjunctive treatment in
patients with ulcerative colitis.
2. Evacuation Enemas:
used to cleanse the bowel.

Are available in disposable plastic squeeze bottles
containing a premeasured amount of enema
solution.

The agents are solutions of sodium phosphate and
sodium biphosphate, glycerin and docusate
potassium, and light mineral oil.
VII) Topical oral (Dental) solutions:
A variety of medicinal substances are employed topically in
the mouth for a number of purposes and in a wide range of
dosage forms.

Teething lotions and toothache drops are medicated.

Others are used for hygienic purposes, such as dentrifices,
denture products, and many of the mouth washes.

Mouth Washes:
Hydroalcoholic solutions. used for two purposes
therapeutic and cosmetic.

Therapeutic to reduce plaque, gingivitis, dental caries
and stomatitis.

Cosmetic to reduce bad breath through the use of
antimicrobial and/ or flavoring agents.

Mouth washes generally contain the following groups of
excipients:

A. Alcohols B. Humectants
C. Surfactants D. Flavors
E. Coloring agents


a. Alcohols: in the range of 10-20%.

It enhances the flavor,
aids in masking the unpleasant taste of active
ingredients,
As a solubilizing agent for some flavoring agents.
May function as preservative.

b. Humectants: 5-20% such as glycerin and sorbitol

Increase the viscosity of the preparation.
Enhance the sweetness of the product and together with
ethanol.
may improve the preservative action.
C. Surfactants: in range of 0.1-0.5%.

They aid in the solubilization of flavors
In the removal of debris.
Usually of the nonionic class Why? as cationic surfactants
import a bitter taste although they provide antimicrobial
properties.

d. Flavors:
To overcome the disagreeable taste.
E.g. peppermint, cinnamon, menthol or methyl salicylate.

e. Coloring agents:
To make the product more palatable and attractive.

VIII) Miscellaneous solutions:
Aromatic waters:
Clear, aqueous solutions saturated with volatile oils or
other aromatic or volatile substances.

Prepared from a number of volatile substances, e.g.
orange flower oil, peppermint oil, rose oil, anise oil,
spearmint oil, camphor and chloroform.

The odors and tastes of aromatic waters are of the
volatile substances from which they are prepared.

Aromatic substances have very low water solubility, and
even though a water may be saturated, its concentration
of aromatic material is still rather small.

Used as perfuming and/or flavoring vehicles.

Deteriorate with time and therefore, made in small
quantities and protected from intense light and excessive
heat by storing in air tight, light resistant containers.

Deterioration may be due to volatilization, decomposition
or mould growth.

Examples include:

Peppermint water and anise water which have carminative
properties

Chloroform water which also acts as preservative.

Preparation of Aromatic waters
a. Distillation process:
Fresh drugs, the proportion of drug to distillate is about
(1:2), or (2:1).

Dried drugs as cinnamon, anise, in (1:10) drug: distillate.

Dried leaf drugs as peppermint, in (3:10) drug: distillate.

After the distillation, excess of oil in the distillate is removed
by filtration.

Multiple distillation: if the volatile principle in the water is in
small quantities, thus the distillate is returned several times
to the still with fresh portions of drug. This is cohobation.
b. Solution process:
Aromatic waters may be prepared by shaking 2 g or 2 ml of
the volatile substance with 1000 ml of purified water.

The mixture is set aside for 12 hours.

Filtered through wetted filter paper.

Made to volume (1000 ml) by adding purified water through
the filter.

Aromatic waters manufactured concentrated and then diluted,
1 to 40 in the final preparation.
Spirits:
Alcoholic or hydroalcoholic solutions of volatile substances.
The alcoholic concentration of spirits is rather high (over
60%). Why? Because of the greater solubility of aromatic or
volatile substances in alcohol than in water.

they contain a greater concentration than aromatic
waters.

When mixed with water or with an aqueous preparation, the
volatile substances present separate from solution and form
a milky preparation.

Used as:
- Flavoring agents
- Medicinally for the therapeutic value of the aromatic solute.
As flavoring agents, they are used to impart the flavor of
their solute to other pharmaceutical preparations.

For medicinal purposes, they may be taken orally,
applied externally, or used by inhalation, depending upon
the particular preparation.

When taken orally, they are mixed with water to reduce
the pungency of the spirit.

Examples of spirits are:

Aromatic ammonia spirit, camphor spirit, compound orange
spirit and peppermint spirit.
Preparation of spirits : depending on the materials
A. Simple solution: majority of spirits are prepared by it:
1- Aqueous ingredients are dissolved in water, oils are
dissolved in alcohol.
2- The aqueous solution is added gradually to the alcoholic
one.
3- Set aside for 24 hours in a cool place, with occasional
shaking, then filter.

B. Solution with maceration: Leaves of drug are
macerated in purified water to extract water soluble matter.
The moist macerated leaves are added to a prescribed
quantity of alcohol.

C. Distillation: as in aromatic waters.
Diluted Acids:
Aqueous solutions prepared by diluting the corresponding
concentrated acids with purified water.

The strength of a dilute acid is percent weight-to-volume
(%w/v), weight in grams of solute per 100 ml of solution.

The strength of a conc acid is percent weight to weight
(%w/w) the number of grams of solute per 100 g of solution.

To prepare a diluted acid from concentrated one, first
calculate the amount of solute required in the diluted
product. Then the amount of concentrated acid required to
supply the needed amount of solute can be determined.

Strength of Diluted acids is 10% w/v, except diluted
acetic acid ( 6% w/v).

The strengths coincide with concentrations for medicinal
or pharmaceutical purposes.

The concentrations of the concentrated acids vary,
according to properties of the solute such as solubility,
stability, and ease of preparation.

e.g. conc H
2
SO
4
is 95 - 98% w/w,
Conc HNO
3
69 -71 % w/w,
and conc H
3
PO
4
is 85 - 88% w/w.

The amounts of concentrated acids to prepare the diluted
acids vary and must be calculated on individual basis.

Diluted acids in medicine are of little use.

Acetic acid because of its antibacterial effects is used as :

1% solution in surgical dressings.

0.25% as an irrigating solution to the bladder.

Spermatocidal in some contraceptive preparations.


EXTRACTIVES
The separation of medicinally active plant or
animal tissues from the inactive or inert
components by the use of selective solvents by
extraction procedures.

Extractives of plants are impure semisolids or
powders, for oral or external use;

Include classes as infusions decoctions, fluid
extracts, tinctures, pilular (semisolid) extracts and
powdered extracts. popularly called galenicals.

Extraction of the therapeutic portion from crude
drugs elimination of inert material by treatment
with a selective solvent, known as menstruum.

It differs from solution that the percent of insoluble matter is
in extraction. The principle methods of extraction are:

(1) Maceration. (2) Percolation.
(3) Digestion. (4) Infusion.
(5) decoction.

The processes of importance as the USP is concerned, are
maceration and percolation; pharmacopoeias refer to such
processes for extraction of active principles from crude
drugs.

Maceration
Solid ingredients are placed in a stoppered
container with the whole of the solvent and allowed
to stand for at least three days (until soluble matter
is dissolved), with frequent agitation,

The mixture is strained, the marc (the damp solid
material) pressed, and combined liquids are
clarified by filtration or by decantation after
standing.


Percolation
To extract the active ingredients in the preparation of
tinctures and fluidextracts.

In the BPC, a percolator (a narrow cone-shaped vessel
open at both ends) is used.

The solid ingredient(s) moistened with an amount of
menstruum are, allowed to stand for four hours in a well-
closed container

The drug mass is then packed into the percolator. Sufficient
menstruum is added to saturate the mass and the top of the
percolator is closed.
When the liquid is about to drip from the neck (bottom) of the percolator,
the outlet is closed.

Additional menstruum is added to give a shallow layer above the mass
and the mixture is allowed to macerate for 24 hours

The outlet of the percolator is opened and the liquid contained is allowed
to drip slowly.

additional menstruum being added as required, until the percolate
measures about three-quarters of the required volume of the finished
product.

The marc is pressed and the expressed liquid is added to the percolate.

Sufficient menstruurn is added to produce the required volume, and the
mixed liquid is clarified by filtration or by allowing it to stand and then
decanting.
Digestion
Maceration with gentle heat during the process of
extraction.

When moderately elevated temperature is not objectionable
and the solvent efficiency is increased thereby.

Infusion
A dilute solution of the readily soluble constituents of crude
drugs.

Fresh infusion are prepared by macerating the drugs for a
short period of time with either cold or boiling water.

An example is conc Compound Gentian Infusion BP 1973.
Decoction
Extracts water soluble and heat-stable constituents from
crude drugs by boiling in water for 15 minutes,

Cooling, straining, and passing sufficient cold water through
the drug to produce the required volume.

Extractives

After a solution of the active constituents of a crude drug is
obtained by maceration or percolation, ready for use as a
medicinal agent, as with certain tinctures or fluidextracts.

or it may be further processed to produce a solid or semisolid
extract.
Tinctures
In the USP as "alcoholic or hydroalcoholic solutions
from vegetable materials or from chemical substance",
example of the latter being Iodine Tincture.

Tinctures of potent vegetable drugs represent the
activity of 10 g. of the drug in each 100 mL of tincture, the
potency is adjusted following assay.

Other tinctures of vegetable drugs represent the
extractive from 20 g of the drug in 100 mL of tincture.

The USP describes two processes for preparing
tinctures, one by percolation as Process P, and the other
by maceration as Process M.

Process P includes a modification so that tinctures that
require assay for adjustment to specified potency may
be thus tested before dilution to final volume.

A tincture prepared by Process P as modified for
assayed tinctures is Belladonna Tincture.

E.g. of tinctures by Process M are Compound Benzoin
Tincture and Sweet Orange Peel Tincture (contains the
extractive from 50 g of sweet orange peel in 100 ml of
tincture).

Fluid extracts
In USP it is "liquid preparations of vegetable drugs,
containing alcohol as a solvent or as a preservative, or both,
each mL contains the therapeutic constituents of 1 g of the
standard drug that it represents".

The USP states that pharmacopoeial fluidextracts are made
by percolation, the official compendia have described
procedures for three percolation methods used in making
fluid extracts.

Process A is a percolation method that can be modified for
fluidextracts that must be assayed.

Process E is an alternative for Process A in which
percolation is conducted on a column of drug much
greater in length than in diameter.

Process D for preparing fluidextracts with boiling water
as the menstruum,

alcohol added as preservative to the concentrated
percolate;
used for preparing Cascara Sagarada Fluidextracts.

The BP and BPC use Liquid Extract for category of
fluidextracts.

Extracts
Defined by USP as "concentrated preparations of vegetable
or animal, drugs obtained by removal of the active constituents
of drugs with suitable menstrua, evaporation of all or nearly all
of the solvent, and adjustment of the residual masses or
powders to the prescribed standards".

Three forms are recognized: - semi liquids liquids of syrup
consistency
-plastic masses, known as pilular or solid extracts
- dry powders, known as powdered extracts.

Extracts, as concentrated forms, used in solid or semisolid
dosage forms.

The USP states that pilular extracts and powdered extracts of
anyone drug are interchangeable medicinally, but each has its
own pharmaceutical advantages.

Pilular extracts are of a consistency that they could
be used in pill masses and made into pills, are
suited for use in ointments and suppositories;

Powdered extracts are for a powdered formulation,
as in capsules, powders, or tablets.

Semi liquid extracts or extracts of a syrupy
consistency used in the manufacture of some
pharmaceutical preparations.


Prepared by extracting the drug by percolation.

The percolate is concentrated by distillation under reduced
pressure; use of heat is avoided where possible because of
potential injurious effect on active constituents.

Powdered extracts that are made from drugs that contain
inactive oily or fatty matter may have to be defatted or
prepared from defatted drug.

Pure Glycyrrhiza Extract USP is an example of a pilular
extract;

Belladonna Extract USP and Hyoscyamus Extract BPC are
examples of powdered extracts (the former is prepared
also as a pilular extract and the latter as a liquid extract).