Water-Insoluble Drug Formulation Stability

Use of these semisolid and solid approaches can potentially alleviate the chemical stability problems sometimes observed for liquid-Llled formulations, and may eventually offer the possibility of development of a tablet dosage form using conventional equipment. Liquid lipid-based formulations, however, generally afford the greatest enhancement of bioavailability for water-insoluble drugs, as well as affording more rapid development for First-in-Human studies. Any decisions on the best formulation route would have to be evaluated on a case-by-case basis. 

Emulsions and suspensions are disperse systems that is, a liquid or solid phase is dispersed in an external liquid phase. While emulsions are sometimes formulated from oily drugs or nutrient oils their main function is to provide vehicles for drug delivery in which the drug is dissolved in the oil or water phase. Suspensions, on the other hand, are usually prepared from water-insoluble drugs for delivery orally or by injection, usually intramuscular injection. An increasing number of modern delivery systems are suspensions - of liposomes or of polymer or protein microspheres, nanospheres or dendrimers, hence the need to understand the formulation and stabilization of these systems. Pharmaceutical emulsions and suspensions are in the colloidal state, that is where the particles range from the nanometre size to visible (or coarse) dispersions of several micrometres. 

Diluents, although commonly presumed inert, do have the ability to influence the stability or bioavailability of the dosage form. For example, dibasic calcium phosphate (both anhydrous and dihydrate forms) is the most common inorganic salt used as a filler-binder for direct compression. It is particularly useful in vitamin products as a source of both calcium and phosphorous. Milled material is typically used in wet-granulated or roller-compacted formulations. The coarse-grade material is typically used in direct compression formulations. It is insoluble in water, but its surface is alkaline and it is therefore incompatible with drugs sensitive to alkaline pFI. Additionally, it may interfere with the absorption of tetracyclines [7]. 

Side effects associated with use of topical tretinoin ointment include transient hyperemia, irritation, or burning. Ocular pharmacokinetic studies in rabbits show low levels of drug in the aqueous humor after topical application of [ H]-tretinoin, with major tissue uptake in the surface epithelium and the iris. Because retinoic acid has poor stability in the presence of light and oxygen and is insoluble in water, its formulations and clinical use are limited. Although it is capable of reversing squamous metaplasia and keratinization, these ocular surface changes are seen only in severe, not mild to moderate, cases of dry eye. 

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