PHARMACEUTICAL SOLUTIONS

Definition:

• A solution is a homogenous one-phase system consisting of two or more components.

• The solvent is that phase in which the dispersion occurs and the solute is that component which is dispersed as small 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.

Advantages of solutions as an oral dosage form:

1. Easier to swallow than solid dosage forms and are therefore particularly acceptable for pediatric and geriatric use.

2. A drug in solution is immediately available for absorption. Thus, the therapeutic response is faster than that from a solid dosage
form which will require a dissolution step before drug absorption takes place.

3. A solution is a homogenous system with a uniform distribution of the drug throughout the preparation. In suspension or emulsion
formulations uneven dosage can occur due to phase separation on storage and shaking is needed before use.

4. Immediately diluted by the gastric contents which reduce irritation to the gastric mucosa caused by high local concentration of
some drugs (aspirin, KCl) if administered as a solid dosage form.

Disadvantages of solutions as oral dosage form:

1. Liquids are bulky and are therefore inconvenient to transport and store. Moreover, immediate loss of the whole product occurs in
case of breakage of the container.

2. Poor stability of the ingredients in aqueous environment of solutions compared to that formulated as a tablet or capsule, which is
particularly important for drugs susceptible to hydrolysis.

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

4. Accurate dosage will depend on the ability of the patients to use a 5 ml spoon or, more rarely, a volumetric dropper. Inaccurate
dosing may lead to loss of the therapeutic efficiency.

5. The unpleasant taste of drugs is more pronounced in solutions than when in a solid form. Sweetening agents & flavors can be used
to make solutions more palatable.

Preservatives

• Microbes will grow in an aqueous solution. Therefore, it is necessary that formulator should add a preservative to the product to
decrease the probability of product contamination.

The major criteria that should be considered in selecting a preservative are as follows:

1. Effective against a wide spectrum of microorganisms

2. Stable for the shelf life of the formulation
3. Nontoxic
4. Nonsensitizing
5. Relatively free of taste and odor
Preservatives may be grouped into a number of classes depending upon their molecular structure, including:

1) Alcohols

• Ethanol is useful as a preservative when it is used as a solvent; however, it needs a relatively high concentration, somewhat
greater than 10% to be effective.

• Propylene glycol is also used as a solvent in oral solutions and topical preparations, and it can function as a preservative in the
range of 15 to 30%. It is not volatile like ethanol.

• Chlorobutanol and phenylethyl alcohol are used in lower concentrations of about 1% for preservative action.

2) Acids

• Benzoic acid has a low solubility in water, about 0.34% at 25°C. The concentration range used for inhibitory action varies from
0.1 to 0.5%. Only the nonionized form is effective, and therefore its use is restricted to preparations with a pH below 4.5.

• Sorbic acid has also a low solubility in water, 0.3% at 30°C. Suitable concentrations for preservative action are in the range of
0.05 to 2%. Its preservative action is due to the nonionized form; consequently, it is only effective in acid media. Because of the
double bonds in its structure, it is subject to oxidation.

3) Esters

• Parabens are esters of p-hydroxybenzoic acid and include the methyl, ethyl, propyl and butyl derivatives. The solubility in water
decreases as the molecular weight increases from 0.25% for methyl ester to 0.02% for the butyl ester. These compounds are
used widely in pharmaceutical products and are effective and stable over a pH range of 4 to 8. They are employed at
concentrations up to a bout 0.2%. Frequently, two eaters are used in combination in the same preparation. This achieves a higher
total concentration, and the mixture tends to be active against a wider range of microorganisms. Their activity is reduced in the
presence of nonionic surface active agents due to binding. In alkaline solutions, ionization takes place and this reduces their
activity; in addition, hydrolytic decomposition of the ester group occurs with a loss of activity.

• The most widely used preservatives are mixture of Methyl parahydroxybezoate in a 0.2% concentration and Propyl
parahydroxybenzoate in a 0.02% concentration. They are suitable for both external and internal use.

4) Quaternary Ammonium compounds

• Benzalkonium chloride is used at relatively low concentration, 0.002 to 0.02%, depending on the nature of the pharmaceutical
product. This class of compounds has an optimal activity over the pH range of 4 to 10 and is quite stable at room temperature.
Because of the cationic nature of this type of preservative, it is incompatible with many anionic compounds such as surfactants
and can bind to nonionic surfactants. It is used generally in preparations for external use or those solutions that come in contact
with mucous membranes.

Methods of preparation:

1) Simple solutions

• Solutions of this type are prepared by dissolving the solute in most of the solvent, mixing until dissolved, then adding sufficient
solvent to bring the solution up to the proper volume. The solvent may contain other ingredients that stabilize or solubilize the
active ingredient.

• Calcium hydroxide topical solution USP (lime water), sodium phosphates oral solution USP, and strong iodine solution USP are
examples. Calcium hydroxide topical solution USP contains, in each 100 ml, not less than 140 mg of Ca(OH)2. The solution is
 prepared by agitating vigorously 3 g of calcium hydroxide with 1000 ml of cool, purified water. Excess calcium hydroxide is
allowed to settle out and the clear, supernatant liquid dispensed.

• An increase in solvent temperature usually implies and increases in solute solubility. This rule does not apply, however, to the
solubility of calcium hydroxide in water, which decreases with increasing temperature. The official solution is prepared at 25°C.

• Solutions containing hydroxides react with the carbon dioxide in the atmosphere.

• Calcium hydroxide topical solution, therefore, should be preserved in well- filled, tight containers, at a temperature not
exceeding 25°C.

• Strong iodine solution USP contains, in each 100 ml, 4.5 to 5.5 g of iodine, and 9.5 to 10.5 of potassium iodide. It is prepared by
dissolving 50 g iodine in 100 ml of purified water containing 100 g of potassium iodide. Sufficient purified water is then added
to make 1000 ml of solution. One g of iodine dissolves in 2950 ml of water. However, solutions of iodides dissolve large
quantities of iodine. Strong iodine solution is, therefore, a solution of polyiodides in excess iodide.

(2n I- +nI2 →I- +1) Doubly charged anions may be found also
2I- + nI2 → I2-(2n+2)

• Strong iodine solution is used in the treatment of iodide deficiency disorders such as endemic goiter.

2) Solution by chemical reaction

• These solutions are prepared by reacting two or more solutes with each other in a suitable solvent. An example is aluminum
subacetate topical solution USP.

• Aluminum sulfate (145 g) is dissolved in 600 ml of cold water. The solution is filtered, and precipitated calcium carbonate (70
g) is added, in several portions, with constant stirring. Acetic acid (160 ml) is added slowly and the mixture set aside for 24
hours. The product is filtered and the magma on the buchner filter is washed with cold water until the total filtrate measures
1000 ml.

• Aluminum subacetate topical solution is used as astringent wash or wet dressing for topical application in treatment of certain
eczematous condition of the skin.

3) Solution by extraction

• Drugs or pharmaceutical necessities of vegetable or animal origin often are extracted with water or with water containing other
substances. Preparations of this type may be classified as solutions but more often, are classified as extracts.

• Aromatic waters, known also as medicated waters, are clear, saturated aqueous solutions of volatile oil or other aromatic or
volatile substances. Their odors and tastes are similar to those of the drugs or volatile substances from which they are prepared.
They are used principally as flavored or perfumed vehicles.

a. Distillation method

• The distillation method consists of placing the odoriferous portion of the plant or drug from which the aromatic water is to
be prepared in a suitable still with sufficient purified water and then distilling most of the water. The aqueous phase, which
may require further clarification, is the product.

• Orange flower water is an example of aromatic water which is prepared directly from fresh plant material and, thus cannot
be prepared by any method other than distillation.
 b. Solution method

• In solution method the volatile substance is agitated with purified water for a period of 15 minutes.

• The mixture is then set aside for at least 12 hours, to ensure saturation, before it is filtered through wetted filter paper.

• A large excess of solute is used (2 ml or 2 gm, liquid or solid as the case may be, per liter) in order to obtain a saturated
solution. The filter paper must be wet to prevent the passage of excess oil into the filtrate and to eliminate absorption of the
dissolved aromatics by the filter.

Pharmaceutical classification of solutions according to vehicle:

Aqueous solution
• A solution is a homogeneous mixture that is prepared by dissolving a solid, liquid, or gas in another liquid and represents a
group of preparations in which the molecules of the solute or dissolved substance are dispersed among those of the solvent. The
narrower definition in this section limits the solvent to water and excludes those preparations that are sweet and/or viscid in
character and non-aqueous solutions, therefore, it includes those pharmaceutical forms that are designated as water, aromatic
waters, aqueous acids, solutions, douches, enemas, gargles, mouthwashes, juices, nasal solutions, otic solutions, and irrigation
solutions.

• Aromatic waters prepared from essential oils, e.g. peppermint water, have been used as carminatives. Chloroform water, is used
in expectorants preparations. Rose water is a perfume.

Aromatic waters are prepared by the following methods:

c. Alternate solution method

• Clarification and time consumed present difficulties in the solution method.

• An alternative method is applied, in which the volatile material is mixed thoroughly with 15 gm. of purified talc. This
mixture is agitated with a liter of purified water for 10 minutes, prior to filtration.

• The talc or other inert material functions as both a filter aid and a distribution agent.

• The time-saving factor is an important advantage.

• As distribution agent, it serves to accelerate the rate of solution by adsorbing and facilitating the breaking up of the aromatic
substance into fine particles, thus increasing the surface area exposed to solvent action.

• As filter aid, it facilities the clarification of the solution.

d. Dilution method
• In an attempt to obviate the difficulties involved in the clarification of aromatic waters, formulas have been developed for
concentrates which are designed to be diluted with an appropriate volume of water when needed.

• An alcoholic solution of the essential oil is mixed with water and talc. The mixture is agitated; after several hours it is
filtered. The concentrate contains between 50 and 55 per cent alcohol by volume. One volume of concentrate is diluted with
39 volumes of water, producing aromatic water which contains less than 1.5 per cent of alcohol.
Concentrated waters, such as peppermint, dill, cinnamon, and caraway, may be prepared as follows:

Essential oil 2 ml
Alcohol 90% 60 ml
Talc 5g
Water to 100 ml

• Dissolve 2 ml. of the volatile oil in 60 ml of 90% ethanol.

• Add sufficient purified water in successive small portions to produce 100 ml.
• Shake vigorously after each addition.
• Add 5 g. of sterilized purified talc, shake occasionally for several hours, and filter.

The aromatic water is prepared by diluting the concentrated with 39 times its volume of water.

Preservation

Aromatic waters will deteriorate with time and should, therefore, be made in small quantities, protected from intense light and
excessive heat, and stored in airtight, light-resistant containers.