Inhibition of crystal growth in a model pharmaceutical semisolid
Crystal growth ofmiconazole andeconazole, two antimycoticimidazole derivatives, were studied with a view to preventing orlimiting crystal growth in atopical semisolid formulation. Crystal growth of the drugs from alcoholic solution was studied, and a ternary (water - cetostearyl alcohol - cetrimide) gel was prepared and considered as a model topical semisolid, principally using rheology and microscopy. The interaction of the drugs with gel components was studied, including interaction of crystalline drug material with aqueous surfactant solutions, and van't Hoff solubility profiles of drugs in nonaqueous components. The effect of gel quality (found to vary with manufacturing temperature) upon rate of crystal growth and crystalline habit was considered, and comparison was made between crystal growth in a ternary system, and in a similarly formulated semisolid emulsion. A range of molecules were screened as potential inhibitors of miconazole crystal growth in the ternary system, and β-cyclodextrin and Dextran-40 were studied in more detail. The additives reduced the rate of crystal growth and altered the proportion of the two habits, but did not prevent growth of crystals in the gels for any practical length of time. It was found that the appearance of a platy habit of miconazole was related to the development of a layered structure within the gel, and the effect of the additives, both in the bulk water phase, and within the layers of swollen gel phase, was considered.