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Solvents used in
Pharmaceutical Preparations
SOME SOLVENTS FOR LIQUID PREPARATIONS
The following agents find use as solvents in the preparation
of solutions
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, a feature especially useful in the extraction of active constituents
from crude drugs. By varying the proportion of the two agents, the active
constituents may be selectively dissolved and extracted or allowed to remain
behind, according to their particular solubility characteristics in the menstruum.
Alcohol, USP, is 94.9% to 96.0% C2H5OH by volume (i.e., v/v) when
determined at 15.56C, the U.S. governments standard temperature for alcohol
determinations. Dehydrated Alcohol, USP, contains not less than 99.5% C 2H5OH
by volume and is used when an essentially water-free alcohol is desired.
Alcohol has been well recognized as a solvent and excipient in the
formulation of oral pharmaceutical products. Certain drugs are insoluble in
water and must be dissolved in an alternative vehicle. Alcohol is often preferred
because of its miscibility with water and its ability to dissolve many waterinsoluble ingredients, including drug substances, flavorants, and antimicrobial
preservatives. Alcohol is frequently used with other solvents, such as glycols
and 6dourless, to reduce the amount of alcohol required. It is also used in liquid
products as an antimicrobial preservative alone or with parabens, benzoates,
sorbates, and other agents.
However, aside from its pharmaceutical advantages as a solvent and a
preservative, concern has been expressed over the undesired pharmacologic and
potential toxic effects of alcohol when ingested in pharmaceutical products,
particularly by children. Thus, the U.S. Food and Drug Administration (FDA)
has proposed that insofar as possible manufacturers of over-the-counter (OTC)
oral drug products restrict the use of alcohol and include appropriate warnings
in the 6dourless. 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%.
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.
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. According to the Internal Revenue Service,
U.S. Treasury Department, the denaturant employed in rubbing alcohol is
formula 23-H, which is composed of 8 parts by volume of acetone, 1.5 parts by
volume of methyl isobutyl ketone, and 100 parts by volume of ethyl alcohol.
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
Multistage Extraction
In the normal maceration process, extraction is incomplete,
since mass transfer ceases when equilibrium is reached. This problem can
be overcome using a multistage process. The equipment needed for this
method is a vessel for the crude drug, a circulating pump, spray distributors
and a number of tanks to receive the extracted solution. The extractor and
tanks are connected with piping and valves as shown in Figure 2, so that any
of the tanks may be connected to the extractor for transfer of the solution.
Each batch of drug is treated several times with solvent and, once a cycle
is in process, the receivers contain solution with the strongest in receiver 1
and the weakest in receiver 3.
Advantages
The crude drug is extracted as many times as there are receivers
(in figure there are three receivers). If more extraction stages are
required, it is only necessary to have more receivers. The last treatment of
the drug before it is discharged is with fresh solvent, giving maximum
extraction. The solution is in contact with fresh drug before removal for
evaporation, giving the highest possible concentration.
Procedure
Fill the extractor with crude drug, add solvent and circulate.
Run off to receiver 1. Refi ll the extractor with solvent and circulate. Run off
to receiver 2. Refi ll the extractor with solvent and circulate. Run off to receiver
3. Remove drug from the extractor and recharge. Return solution from
receiver 1 to the extractor. Remove for evaporation. Return solution from
receiver 2 to the extractor and circulate. Run off to receiver 1. Return solution
from receiver 3 to the extractor and circulate. Run off to receiver 2. Add
fresh solvent to the extractor and circulate. Run off to receiver 3. Remove
drug from the extractor and recharge. Repeat cycle.
Extraction Battery
In the normal percolation process, the percolate is a very dilute
solution, while the ideal situation is to obtain the maximum concentration
possible. Continuous extraction devices of battery type are used when large
amounts of a single material are handled. Such devices can be achieved by
treating percolation as a multistage process. In an extraction battery process,
a series of vessels is used and extraction is semicontinuous.
Equipment
An extraction battery consists of a number of vessels with interconnecting
piping. Vessels are so arranged that solvent can be added
to and the product taken from any vessel. These vessels can, therefore, be
made into a series with any of vessels as the first of the series. The use
of an extraction battery is illustrated in Figure 3, which shows the simplest
arrangement of three vessels.
References:
Ansels Pharmaceutical Dosage Forms and Drug Delivery
Systems (Page 335-336) (07-04-2016)