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PHARMACEUTICAL
DOSAGE FORM “I“
LIQUID DOSAGE FORMS

10/17/2020 Department of pharmaceutics

 MARKS DISTRIBUTION
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 Periodical Quizzes 15.00 %

 Oral Examination 10.00 %
 Practical Examination 25.00 %
 Final-term Examination 50.00 %
The curriculum will be distributed on about 12 lectures
(2 hour weekly )
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 Course specification
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Pharmaceutical dosage form I

This course will cover:
*Pharmaceutical solutions,
* Coarse dispersions,
*Suspensions, colloids and emulsions.

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 Dosage forms classification

Dosage forms
classification

Liquid Dosage Semisolid D.F.

Solid Dosage
forms Ointment Molded D.F. Sterile D.F.
form
Solution Cream Suppositories Injection
Tablets
Suspension Paste Pessaries Ophthalmics
capsules
Emulsion gel
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Solutions
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 Introduction
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An understanding of the properties of solutions, the factors that affect solubility and the
process of dissolution is essential because of the importance of solutions in so many areas of
pharmaceutical formulation.
Solution is a homogenous one-phase system consisting of two or more components. The
solvent, or mixture of solvents, is phase in which the dispersion occurs, and the solute is the
component which is dispersed as molecules or ions in the solvent.
In general the solvent is present in the greater amount, but there are several exceptions. For
example, Syrup BP contains 66.7% w/w of sucrose as the solute in 33.3% w/w of water as the
solvent.
For most pharmaceutical solutions the solvent system is likely to be liquid, and the solute
will be either a liquid or a solid. Solid dispersions, in which both solute and solvent are solids,
are used for the improvement of the bioavailability of poorly soluble drugs.
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 Introduction
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Solutions of gases in liquids are characteristic of aerosols, in which the propellant gas is
dispersed or dissolved in the solvent under pressure. On actuation of the valve mechanism the
propellant ejects the product from the container. The propellant immediately evaporates, leaving
the active agent in the form of tiny droplets or particles or within a foam structure.
Type of Solution: Example Solute Solvent
Gas dissolved in gas: dry air oxygen nitrogen
Gas dissolved in liquid: carbonated water carbon dioxide Water
Gas dissolved in solid: floating soap air soap
Liquid dissolved in gas: moist air water air
Liquid dissolved in liquid: vinegar acetic acid water
Liquid dissolved in solid: amalgum mercury silver
Solid dissolved in gas: Mothballs in Air Moyhball Air
Solid dissolved in liquid: sweet tea sugar Tea
Solid dissolved in solid: bronze Tin Copper 10/17/2020
12 kerat gold copper gold
 Introduction
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Based on their composition, solutions classified as:

1- Syrups; aqueous solutions containing a sugar.
2-Elixirs; sweetened hydroalcoholic (combinations of water and
ethanol) solutions.
3-Aromatic waters; aromatic materials dissolved in aqueous.
4-Spirits; aromatic materials dissolved in alcohol
5-Tinctures or fluidextracts; Solutions prepared by extracting active
constituents from crude drugs. Tinctures may also be solutions of
chemical substances dissolved in alcohol or in a hydroalcoholic
solvent. 10/17/2020
 Classification:
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Based on route of administration and pharmaceutical use, solution classified as:

I-Solutions for Internal Use:-
1- Oral solutions, syrups, elixirs, spirits, and tinctures are prepared and used for the
specific effects of the medicinal agents they carry. In these preparations, the medicinal
agents are intended to provide systemic effects. The fact that they are administered in
solution form usually means that they are soluble in aqueous systems and their absorption
from the gastrointestinal tract into the systemic circulation may be expected to occur more
rapidly than from suspension or solid dosage forms of the same medicinal agent.
II-Solutions for External use:-
1- Injection solutions; sterile and pyrogen free and intended for parenteral administration.
2- Topical solution; preparation intended for topical application such as paints, otics, lotions
and liniments
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 Advantages and disadvantages of solution
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Advantages of solution as dosage form:

1-Therapeutic agents can easily be administered orally to individuals who have difficulty in swallowing, e.g.
elderly, patients, infants.
2- A drugs in the form of solutions are immediately available for absorption with fast therapeutic response.
3- Reduce the irritation of the gastric mucosa caused by some drugs.
4- A dose uniformity is obtained.
5-Taste-masking of bitter therapeutic agents may be readily achieved.
Disadvantages of solution as dosage form:
1- Liquids are bulk and not easy to transported and storage.
2- Require the addition of sweeteners and flavors to mask the unpleasant taste of some drugs.
3- Enhance growth of microorganisms , therefore it require the incorporation of preservatives.
4-Low ingredients stability.
5-Dose inaccuracy.
6-The poor solubility of certain therapeutic agents may prohibit their formulation as pharmaceutical
solutions. 10/17/2020
 Solvents for aqueous solution
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Definition of aqueous solution: It is a homogenous mixture that is prepared by dissolving a
solid, liquid or gases (dissolved substance) in water (solvent). It includes those pharmaceutical
forms that are designed with water, aromatic waters, aqueous acids, as solutions, douches,
enemas, gargles, mouthwashes, juices, nasal solutions, otic solutions, and irrigation solutions.
I-Water: Water is the solvent most widely used as a vehicle for pharmaceutical products,
because of its physiological compatibility and lack of toxicity. It possesses a high dielectric
constant, which is essential for ensuring the dissolution of a wide range of ionizable materials.
In some cases this property may be an advantage, but the lack of selectivity can be responsible
for aqueous solutions containing unwanted substances such as inorganic salts and organic
impurities. This is one reason why water is rarely used for the extraction of active constituents
from vegetable sources. Naturally occurring water contains dissolved minerals indigenous to
the region, such as calcium, magnesium, iron+3, sodium and potassium ions. Hard water
contains calcium and magnesium cations. 10/17/2020
 I- Waters
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Water

Water for
Sterile water for injection free Bacteriostatic
Potable water Purified water from dissolved water
injection
gasses

Ion-exchange or
Distillation de-ionized water Reverse osmosis

Acid or cation Base or anion

exchange step exchange step
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 Solvents for aqueous solution
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a- Potable water (Tap water): For many preparations potable water can
be used. This is water freshly drawn from the mains system and
suitable for drinking. Potable water is unsuitable for certain
pharmaceutical purposes due to its possible bacterial contamination.
b-Purified water (BP): Purified water must used in all occasions where
the presence of salts and microorganisms (often dissolved in potable
water) is undesirable. Purified water is normally prepared by:
1- Distillation: which has been freshly boiled and cooled
immediately before use to destroy any vegetative microorganisms that
might be present. It is a widely used method for separating mixtures
based on differences in the conditions required to change the phase of
components of the mixture.
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 Solvents for aqueous solution
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To separate a mixture of liquids, the liquid can be heated to force components, which
have different boiling points, into the gas phase. The gas is then condensed back into liquid
form and collected. Repeating the process on the collected liquid to improve the purity of the
product, the process which is called double distillation.

2- Deionization (ion exchange): The process includes remove of the major impurities
in water using cations (acid) exchanger (the replacement of cations in solution with
hydrogen ion) and anion ( base) exchanger (the replacement of anions in solution with
hydroxyl group).
CaSO4 + H2R CaR + H2SO4 (cationic)
H2SO4 + 2AOH A2SO4 + 2 H2O (anionic)

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 Solvents for aqueous solution
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3- Reverse osmosis: It is a membrane separation process in which feed water flows along
the membrane surface under pressure. Purified water permeates the membrane and is
collected, while the concentrated water, containing dissolved and undissolved material
that does not flow through the membrane, is discharged to the drain. The
key requirements of Reverse Osmosis process are a membrane and water under a
pressure. Other requirements include pre-filtration to remove suspended impurities and
carbon to remove chlorine (damages the membrane). Most membranes remove 90-99%
of the dissolved impurities depending on the impurity and the composition of water.
Reverse osmosis systems remove salts, microorganisms and many high molecular weight
organics. System capacity depends on the water temperature, total dissolved solids in
feed water, operating pressure and the overall recovery of the system.
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 Solvents for aqueous solution
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c)Water for injection: must be used for the formulation of parenteral solutions and is obtained
by sterilizing pyrogen-free distilled water immediately after its collection.
d)Water for injection free from dissolved gases: water free from CO2 or O2 are used to
dissolve special drugs that are sensitive to these gases. It is obtained by boiling pyrogen-free
distilled water for 10 min and immediately sealing in its final container and then sterilized.
e)Bacteriostatic water for injection: It is a sterile pyrogen-free water contains one or more
suitable antimicrobial agents.
f) Sterile water for irrigation: Water for injection that has been sterilized and packaged. It
contains no antimicrobial agent or other added substance.
II- Aromatic water (Hydrolata): Known also as medicated water, which is clear, saturated
with volatile or other aromatic substances ( peppermint, chloroform and rose), has a pleasant
taste and odor.
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 Solvents for aqueous solution
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Due to its deterioration by time, it must be protected from direct sun light, excess heat and
stored in air-tight container. It is prepared by one of the following methods:
a) Distillation method (EP): In this method, the plant portions of interest are placed with the
sufficient amounts of purified water in a still, and the produced distillate is the required
aromatic water.
b) Solution method (EP): The aromatics are agitated with the purified water for 15 min, and
the mixture set aside for 12 h and then filtered through a wet filter paper.
c) Alternate solution method (EP): In which the volatile material is mixed with purified talc
powder, and then agitated with purified water for 15 min. Talc acts as distributing agent that
increase surface area of volatile oil exposed to the solvent leading to enhance dissolution and
aids filtration.
d) Dilution method (EP): It is used to prepare a concentrated alcoholic solution of volatile oils
which diluted with purified water when needed. 10/17/2020
 Solvents for aqueous solution
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Example of this, the preparation of peppermint, caraway and cinnamon concentrates as

follow: 2 ml of the essential oil is dissolved in 60 ml of 90% ethyl alcohol, a successive
small portions of purified water are added with shaking to produce 100 ml total volume. Then
after, 5 g of sterilized purified talc is added with occasional shaking for several hours and
filter. Upon uses, one volume of concentrate is diluted with 39 volume of purified water. The
produced solution contain less than 1.5% alcohol.
Preservation of Aromatic Waters
Aromatic waters should be freshly prepared and should not be made in larger quantities
than can used within a reasonable time as they deteriorate when kept too long, usually
through the development of microorganisms, all traces of their agreeable odour disappearing.
No preservative should be added to aromatic waters. If they become cloudy or otherwise
deteriorate, they should be discarded.
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 Solvents for aqueous solution
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Stability of Aromatic Waters

*Many of the aroma bearing solutes are oxidized by exposure to light.
*High temperature cause aromatic waters to loss some of their desirable characteristics.
*Since aromatic waters are saturated solutions, lowering the temperature caused separation
of the aromatic component producing cloudiness.
*The aromatic substances may be salted out when the water is used as a vehicle for drugs
which are electrolytes and the insoluble materials collect on the top of the liquid,
imparting a burning taste to the first dose..
Incompatibility of Aromatic Waters
In the presence of very soluble salts, they will salt out the insoluble portion of the volatile
principle in aromatic water. This difficulty can be overcomes by replacing part of the aromatic
water with purified water.
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 Solvents for aqueous solution
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Uses of aromatic waters

1- They provide pleasantly flavoured medium for the administration of water-
soluble medicinals. Flavoured waters certainly added to the elegance of
prescriptions, whether simple or complex.
2- They also mask the undesirable tastes in suspensions and emulsions.
3- Several aromatic waters are not used as vehicles for oral medication, e.g., Rose
water, Hammemlis water, and camphor water. Rose water is a perfume,
Hammemlis water is used as astringent in after shave lotions and other cosmetic
products, Camphor water is frequently prescribed in eye drops and eye washes
for its slight refreshing and stimulating effects.

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 Solvents for aqueous solution
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III- Aqueous acids: The official undiluted organic and inorganic acids
(e.g. have some pharmaceutical applications. They provide in the
form of concentrated solutions with varied strength expressed in the
form of percent by weight (W/W).example of the aqueous acid is
1% acetic acid used as a solvent for many ingredient as chitosan

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 Solvents for non-aqueous solution
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The non-aqueous solvents are used when the active ingredients not insure
complete solubility or unstable in aqueous solvents. Also, the non-aqueous
solvents over an advantage over the aqueous in that it can be used for depot
therapy (releasing the drugs slowly). It is essential that in choosing a suitable
solvent, its toxicity, irritancy and sensitizing potential are taken into account, as
well as its flammability, cost, stability and compatibility with other excipients. A
far wider range of solvents are available for use as part of the manufacture of
pharmaceuticals. In these instances the solvent is removed before packaging and
is therefore not present in the final products ( such as acetone, light petroleum and
chloroform)
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 Solvents for non-aqueous solution
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I- ALCOHOL, USP: ETHYL ALCOHOL, ETHANOL, C2H5OH

Next to water, alcohol is the most useful solvent in pharmacy. It is used as a
primary solvent for many organic compounds. Together with water, it forms a
hydroalcoholic mixture that dissolves both alcohol-soluble and water-soluble
substances.
By varying the proportion of the two agents, the active constituents may be
selectively dissolved and extracted. Alcohol, USP, is 94.9% to 96.0% C2H5OH by
volume (i.e., v/v) when determined at 15.56°C. Dehydrated Alcohol, USP,
contains not less than 99.5% C2H5OH by volume and is used when an essentially
water-free alcohol is desired.
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Alcohol is often preferred because of its miscibility with water and its ability to
dissolve many water-insoluble ingredients, including drug substances, flavorants,
and antimicrobial preservatives. It is also used in liquid products as an
antimicrobial preservative alone or with parabens, benzoates, sorbates, and other
agents.
For OTC oral products intended for children under 6 years of age, the
recommended alcohol content limit is 0.5%; for products intended for children 6
to 12 years of age, the recommended limit is 5%; and for products recommended
for children over 12 years of age and for adults, the recommended limit is 10%.

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 Solvents for non-aqueous solution
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II- DILUTED ALCOHOL, NF

Diluted Alcohol, NF, is prepared by mixing equal volumes of Alcohol, USP, and
Purified Water, USP. The final volume of such mixtures is not the sum of the
individual volumes of the two components because the liquids contract upon
mixing; the final volume is generally about 3% less than what would otherwise be
expected.
Thus, when 50 mL of each component is combined, the resulting product measures
approximately 97 mL. It is for this reason that the strength of Diluted Alcohol,
NF, is not exactly half that of the more concentrated alcohol but slightly greater,
approximately 49%. Diluted alcohol is a useful hydroalcoholic solvent in various
pharmaceutical processes and preparations.
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 Solvents for non-aqueous solution
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III- RUBBING ALCOHOL

Rubbing alcohol contains about 70% ethyl alcohol by volume, the remainder consisting
of water, denaturants with or without color additives and perfume oils, and stabilizers. Each
100 mL must contain not less than 355 mg of sucrose octaacetate or 1.4 mg of
denatonium benzoate, bitter substances that discourage accidental or abusive oral ingestion.
The use of this denaturant mixture makes the separation of ethyl alcohol from the
denaturants virtually impossible with ordinary distillation apparatus. This discourages
the illegal removal for use as a beverage of the alcoholic content of rubbing alcohol.
The product is volatile and flammable and should be stored in a tight container
remote from fire. It is employed as a rubefacient externally and as a soothing rub for
bedridden patients, a germicide for instruments, and a skin cleanser prior to injection. It is
also used as a vehicle for topical preparations.
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