Non-Aqueous Pharmaceutical Solutions Lecture Notes PDF

Dina Omar, PhD Lecturer of Pharmaceutics and Industrial Pharmacy 1 Uses of non-aqueous preparations If the dr...

Dina Omar, PhD Lecturer of Pharmaceutics and Industrial Pharmacy 1 Uses of non-aqueous preparations If the drug is unstable Oily solutions of If the drug is not in aqueous medium, drugs are often used completely soluble in it may be necessary for depot therapy e.g. aqueous medium. to use an alternative injections in muscles non-aqueous solvent. Routes of administration Internal oral products may contain ethanol, glycerol, propylene glycol, certain oils. (in permitted amounts) Solvents such as acetone and petroleum ether are not used for internal products. (external use only) For parenteral products, the choice is very limited (water- certain oils eg. corn, sesame oil). 1  Non-Aqueous Pharmaceutical Solutions Alcoholic or Ethereal Glycerin Oleaginous Hydroalcoholic solutions solutions solutions solutions Elixirs and Liniments, Collodions Glycerites medicated oils, Spirits oleo-vitamins 1- Elixirs Clear pleasantly flavored, sweetened hydroalcoholic liquids intended for oral use Elixir Composition Main ingredients Secondary Ethanol & water ingredients Each elixir requires a specific blend Glycerin & syrups to: of alcohol and water to maintain all 1- ↑ solubility components in solution 2- Sweetening agent Alcoholic content vary from elixir Propylene glycol as containing small quantity to others substitute for glycerin & containing large quantity. alcohol e.g. Aromatic elixir (21-23% alc.) Flavoring agent, Compound benzaldehyde elixir (3- preservatives 5% alc) N.B. Elixirs containing over 12% of 4 alcohol are usually self-preserving 2  Elixirs Incompatibilities: Alcohol in elixir precipitates tracaganth, acacia, agar & inorganic Syrups Eixirs salts from aqueous solutions. If water is added to elixir  pptn. of ingredient due to reduced alcohol content in final preparation. Elixirs cause separation of extractive matter from tincture & fluid extract (solutions in alcohol) due to reduction of alcohol content. 5 Preparation of elixirs: When elixir contains alcohol & water-soluble ingredients: Dissolve water- Add & solubilize Prepare alcoholic soln. soluble substances sucrose in aq. solution containing alcohol Add aqueous solution in part of water soluble ingredients to alcoholic solution (sucrose ↑ viscosity & ↓ solubilizing Filter, Complete property of water so must be added volume after primary solution is done). Elixirs must be brilliantly clear so they must be filtered after few hours of standing or if necessary subjected to clarifying action of talc which absorbs excessive amounts of oils 6 3  Types of Elixirs Non-medicated Medicated (aromatic) elixirs elxirs Addition of a Antihistamine elixir therapeutic agent to Dilution of an existing Relief of certain allergic a pleasant tasting medicated elixir. disorders vehicle Phenobarbital Elixir - Contains 14% of alcohol ( mim. required to keep the phenobarbital in solution. Glycerin is added to enhance phenobarbital solubility Digoxin Elixir 7 10% alcohol 2- Spirits (Essence) Alcoholic or hydroalcoholic solution of volatile substances, used internally (62-68% alc.) or by inhalation (80-87% alc.) or as flavor. May be used to prepare It should be stored in tight, light aromatic water. resistant container in cool place why? To prevent evaporation of alcohol & volatile drugs. Methods of preparation Simple Solution by Chemical Distillation solution maceration reaction 8 4  1- Simple solution: e.g. Aromatic ammonia spirit (respiratory stimulant taken by inhalation) Rx (NH4)2CO3  NH3 + CO2 + water Ammonium carbonate Strong ammonia soln. (NH4OH) Lemon oil Strong ammonia solution ↓ hydrolysis Lavender oil (decomposition) of ammonium carbonate Nutmeg oil decrease loss of dissolved gas  ↑ stability. Alcohol Water Aromatic ammonia spirit can not be mixed with preparation containing alkaloid (e.g. codeine phosphate ) → ammonium phosphate is formed & if alcohol content of final mixture is too low  codeine will ppt. 9 2- Solution by maceration : Filter Filter Leaves of drug are Volatile oil is added to the filtered liquid. Add alcohol to the macerated in water (e.g. peppermint spirit USP) leaves To remove water It is green in color due to chlorophyll. soluble matter Why maceration of leaves in alcohol? To acquire the green color. Spirits’ Incompatibility on dilution with pptn. of Spirit is of high water/liquids of dissolved alcohol strength low alc. content substance of spirit Spirit cause ppt. of salt from aqueous solution due to low solubility of salts in alcohol. 10 5  3- Oleovitamins Vitamin concentrate (Vitamins A&D) in fish liver oil or in edible vegetable oil. Vitamins are unstable in presence of rancid oil so should be stored in: Small tight container Protected Under from vacuum light. or inert gas 11 4- COLLODIONS Are liquid preparations They are applied to the skin by containing pyroxylin (a means of a soft brush or other nitrocellulose derivative) in a suitable applicator and, when the mixture of ethyl ether and ether and ethanol evaporated, ethanol external use. they leave a film of pyroxylin on the surface. The official medicated collodion, Salicylic Acid Collodion USP, contains 10 % w/v of Salicylic Collodion is made flexible by the Acid in Flexible Collodion USP addition of castor oil and and is used as a keratolytic camphor. agent in the treatment of corns and warts. 6  5- GLYCERITES Glycerins or glycerites are solutions or mixtures of medicinal substances in not less than 50% by weight of glycerin. Glycerin is used as In Otic Solutions, Glycerins are Most of the the sole solvent for glycerin alone is hygroscopic and glycerins are the preparation of used to aid in the should be: stored in extremely viscous. Benzocaine Otic removal of tightly closed Solution USP. cerumen. containers. 6- LINIMENTS Are solutions or mixtures They are intended for of various substances in external application and oil, alcoholic solutions of should be so labeled soaps, or emulsions. (red). They are applied with The oil or soap base rubbing to the affected providing for ease of area, application and massage. Alcoholic liniments are used for their rubefaciant & counterirritant effects. Liniments should not be Such liniments penetrate applied to skin that are the skin more readily broken. than do those with an oil base only. 7  15 Galenical extraction Extraction is the operation by which soluble constituents of crude drugs are dissolved in a suitable solvent and separated from unwanted, insoluble materials eg., albumin, cellulose, gum , pectin, starch and sugars. Solvent= menstruum Filter Crude drug Extractive Marc Preparation obtained Insoluble residue by extraction remaining after extraction In drug extraction the solvent should extract the maximum amount of the active substances and a minimum amount of the inert substances because inert extracted substances affect the finished product: Oxidation of inert Inert substances may be substances cause hydrolyzed to insoluble darkening of Galenical compounds that extractives on aging precipitate. 16 8  Selection of menstruum Extracts considerable amount of substances that are liable to hydrolysis or oxidation Extracts mucilaginous and carbohydrate materials which form viscous solutions Water that are difficult to process and are good media for microbial growth Good solvent for alkaloids, glycosides, and resins; it does not dissolve inert gums, sugars, and albumin. Inhibits enzymatic action and microbial growth (preservative effect) Alcohol Not used alone as menstrum because it is expensive Combines the advantages of alcohol and water without the disadvantages of Hydro- water alcoholic solvent Good solvent for many plant substances Cosolvent with water/alcohol because of its ability to extract and then prevent inert materials from precipitating upon standing Glycerin Preservative action thus contribute to stability of final product 17 Methods of extraction 1- Maceration The marc washed free of extractive Agitate repeatedly over a by the additional passage of period of 2 to 14 days menstrum through the strainer or filter Straining and/or filtration For drugs containing little or no cellular Properly comminuted drug is soaked in the material, such as benzoin, aloe and tolu, menstrum till the cellular structure is softened and which dissolve almost completely in the penetrated by the menstrum and the soluble menstruum, maceration is the most efficient constituents are dissolved method of extraction. 2- Percolation The flow of the menstruum over the drug A comminuted drug is extracted of column is generally downward to the exit its soluble constituents by the orifice, drawn by the force of gravity and slow passage of a suitable the weight of the column of liquid. solvent through a column of the drug. The drug is packed in a In more sophisticated percolation apparatus, special extraction apparatus additional pressure on the column is exerted termed a percolator, with positive air pressure at the inlet and extractive = percolate. suction at the outlet or exit. Combination of maceration and percolation is employed in extraction of a crude drug. The drug is 18 macerated first to soften plant tissues and to dissolve much of the active constituents, then percolation is conducted to achieve separation of the extractive from the marc. 9  3- Digestion 4- Infusion 5- Decoction Form of maceration A dilute solution of Process which in which gentle heat the readily soluble extracts water is used during the constituents of crude soluble and heat- process of drugs. Fresh stable constituents extraction, used infusions are from crude drugs by when moderately prepared by boiling in water for elevated temp. Is not macerating the 15 minutes, cooling, objectionable drugs for a short straining, and time with either cold passing sufficient or boiling water. cold water through the drug to produce the required volume 19 Extractives Tinctures Fluid Extracts Galenical Oleoresins extracts resins Extractive is ready for use as a Extractive is further processed to produce a solid or medicinal agent semisolid extract 1- Tinctures Alcoholic or hydroalcoholic Depending upon the Tinctures prepared from solutions prepared from preparation, tinctures potent drugs are usually vegetable materials or contain alcohol in 10% tinctures eg., Digitalis from chemical substances amounts ranging from tincture and belladonna (eg., Iodine tincture). 15 - 80%. tincture Tinctures prepared from Tinctures of vegetable materials are prepared by 2 chemical substances eg., processes, maceration eg. Compound benzoin tr. And Iodine tr. are prepared by percolation eg. Belladonna tr. simple solution of chemical agent in solvent. The alcoholic content protects against microbial growth and keeps the alcohol-soluble extractives in solution. In addition to alcohol, other solvents as glycerin may be used. 20 10  2- Fluid extracts Liquid preparations of vegetable drugs, prepared by percolation. Because of their They contain alcohol as a concentrated nature, they They are too bitter tasting solvent or as a preservative, are too potent to be taken and unpalatable to patients. or both, and are made so safely in self-administration Therefore, they are either that each ml contains the by the patient and are used modified by the addition of therapeutic constituents of pharmaceutically as the flavoring or sweetening 1 g of the standard drug drug source component of agents. that it represents. other liquid dosage forms, such as syrups. 3- Extracts Concentrated preparations of vegetable or animal drugs Collection of the Adjustment of the active constituents Evaporation of all residual masses or with suitable or nearly all of powders to the menstrua by the solvent, prescribed percolation standards. Semi-liquids Plastic (pilular) Dry powder masses liquids of syrup Ointments/ Capsules/Powders/ consistency Suppositories Tablets 21 4- Galenical resins Evaporation Pour on water Percolation of a crude drug Resin Resin ppt with an alcoholic solvent It containst alcohol- soluble, water-insoluble constituents of crude drug 5- Oleoresins Liquid galenical extractives of natural oils and resins extracted by percolation, generally using acetone or ether as a solvent. 22 11  23 12