Solvents

 

Solvents

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 15.56°C, the U.S. government’s standard temperature for alcohol determinations.

•       Dehydrated Alcohol, USP, contains not less than 99.5% C2H5OH 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 water-insoluble ingredients, including drug substances, flavorants, and antimicrobial preservatives.

•       Alcohol is frequently used with other solvents, such as glycols and glycerin, 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 labeling.

•       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 octa- acetate 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 cleanser prior to injection. It is also used as a vehicle for topical preparations.

•       Synonym: alcohol rubbing compound.

GLYCERIN, USP (GLYCEROL), CH2OH•CHOH•CH2OH

•       Glycerine is a clear syrupy liquid with a sweet taste.

•        It is miscible with both water and alcohol. As a solvent, it is comparable with alcohol, but because of its viscosity, solutes are slowly soluble in it unless it is rendered less viscous by heating.

•       Glycerine has preservative qualities and is often used as a stabilizer and as an auxiliary solvent in conjunction with water or alcohol.

•        It is used in many internal preparations.

ISOPROPYL RUBBING ALCOHOL

•       Isopropyl rubbing alcohol is about 70% by volume isopropyl alcohol, the remainder consisting of water with or without colour additives, stabilizers, and perfume oils.

•       It is used externally as a rubefacient and soothing rub and as a vehicle for topical products.

•       This preparation and a commercially available 91% isopropyl alcohol solution are commonly employed by diabetic patients in preparing needles and syringes for hypodermic injections of insulin and for disinfecting the skin.

PROPYLENE GLYCOL, USP, CH3CH(OH)CH2OH

•       Propylene glycol, a viscous liquid, is miscible with water and alcohol.

•       It is a useful solvent with a wide range of applications and is frequently substituted for glycerin in modern pharmaceutical formulations.

PURIFIED WATER, USP, H2O

•       Naturally occurring water exerts its solvent effect on most substances it contacts and, thus, is impure, containing varying amounts of dissolved inorganic salts, usually sodium, potassium, calcium, magnesium, and iron; chlorides; sulfates; and bicarbonates, along with dissolved and undissolved organic matter and microorganisms.

•       Water found in most cities and towns where water is purified for drinking usually contains less than 0.1% of total solids, determined by evaporating a 100-mL sample to dryness and weighing the residue (which weighs <100 mg).

•       Drinking water must meet the U.S. Public Health Service regulations with respect to bacteriologic purity.

•       Acceptable drinking water should be clear, colorless, odorless, and neutral or only slightly acidic 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).

•       Ordinary drinking water from the tap is not acceptable for the manufacture of most aqueous pharmaceutical preparations or for the extemporaneous compounding of prescriptions 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.

•        Its use is permitted in washing, in extraction of crude vegetable drugs, in preparation of certain products for external use, and when the difference between tap water and purified water is of no consequence.

•       . Naturally, when large volumes of water are required to clean pharmaceutical machinery and equipment, tap water may be economically employed so long as a residue of solids is prevented by using purified water as the final rinse or by wiping the water dry with a meticulously clean cloth.

Method For Purification of Water USP

Purified Water, USP, is obtained by

•       1. Distillation,

•       2. Ion exchange treatment,

•       3. Reverse osmosis,

•       It is prepared from water complying with the federal Environmental Protection Agency with respect to drinking water.

•       Purified Water, USP, has fewer solid impurities than ordinary drinking water.

•       When evaporated to dryness, it must not yield more than 0.001% of residue (1 mg of solids per 100 mL of water).

•       Thus, purified water has only 1% as much dissolved solids as tap water.

•        Purified Water, USP, is intended for use in the preparation of aqueous dosage forms except those intended for parenteral administration (injections).

•       Water for Injection, USP; Bacteriostatic Water for Injection, USP; or Sterile Water for Injection, USP, is used for injections

Distillation Method

•       Many stills in various sizes and styles with capacities ranging from about 0.5 to 100 gallons of distillate per hour are available to prepare purified water.

•       Generally, the first portion of aqueous distillate (about the first 10% to 20%) must be discarded because it contains many foreign volatile substances usually found in urban drinking water, the usual starting material.

•       Also, the last portion of water (about 10% of the original volume of water) remaining in the distillation apparatus must be discarded and not subjected to further distillation because distillation to dryness would undoubtedly result in decomposition of the remaining solid impurities to volatile substances that would distill and contaminate the previously collected portion of distillate.

Ion Exchange Method

•       On a large or small scale, ion exchange for the preparation of purified water offers a number of advantages over distillation.

•       For one thing, the requirement of heat is eliminated and with it, the costly and troublesome maintenance frequently encountered in the operation of the more complex distillation apparatus.

•       Because of the simpler equipment and the nature of the method, ion exchange permits ease of operation, minimal maintenance, and a more mobile facility.

•       Many pharmacies and small laboratories that purchase large volumes of distilled water from commercial suppliers for use in their work would no doubt benefit financially and in convenience through the installation of an ion exchange demineralizer in the work area.

•       The ion exchange equipment in use today generally passes water through a column of  cation and anion exchangers consisting of water insoluble synthetic polymerized phenolic, carboxylic, amino, or sulfonated resins of high molecular weight.

•       These resins are mainly of two types:

•        (a) the cations, or acid exchangers, which permit the exchange of the cations in solution (in the tap water) with hydrogen ion from the resin;

•       (b) the anions, or base exchange resins, which permit the removal of anions.

•       These two  processes are successively or simultaneously employed to remove cations and anions from water.

•       The processes are indicated as follows, with M+ indicating the metal or cation (as Na+) and the X− indicating the anion (as Cl−).

•      Cation exchange:

 H-resin+M + X +H2O → M-resin+H + X +H2 O(pure)

•      Anion exchange:

 Resin-NH2 +H + X +H2O →2 Resin-NH2* HX+H2O(pure)

Water purified in this manner, referred to as demineralized or deionized water, may be used in any pharmaceutical preparation or prescription calling for distilled water.

Reverse Osmosis

•       Reverse osmosis is one of the processes referred to in the industry as cross-flow (or tangential flow) membrane filtration .

•       In this process, a pressurized stream of water is passed parallel to the inner side of a filter membrane core.

•       A portion of the feed water, or influent, permeates the membrane as filtrate, while the balance of the water sweeps tangentially along the membrane to exit 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.

•       Whereas in osmosis the flow through a semipermeable membrane is from a less concentrated solution to a more concentrated solution, the flow in this cross-flow system is from a more concentrated to a less concentrated solution; thus the term reverse osmosis.

•       Depending on their pore size, cross-flow filter membranes can remove particles defined in the range of microfiltration (0.1 to 2 μm, e.g., bacteria); ultrafiltration (0.01 to 0.1 μm, e.g., virus); nanofiltration (0.001 to 0.01 μm, e.g., organic compounds in the molecular weight range of 300 to 1,000); and reverse osmosis (particles less than 0.001 μm). Reverse osmosis removes virtually all viruses, bacteria, pyrogens, and organic molecules and 90% to 99% of ions.