Grinding Effect on Some Pharmaceutical Properties of Drugs by Adding β-Cyclodextrin

Abstract

The effect of grinding on the physicochemical properties of ground mixtures of crystalline drugs (acetaminophen, warfarin, indomethacin, diazepam and hydrocortisone acetate) with 3-cyclodextrin was studied by IR analysis, x-ray diffraction method and thermal analysis. The crystallinities of drugs decreased with increasing grinding time and became amorphous or nearly amorphous, which depended on drug moiety and cavity size of 3-cyclodextrin. The result indicates that acetaminophen became amorphous and only formed an inclusion complex in the ground mixture with 3-cyclodextrin, although all five drugs interacted with 3-cyclodextrin in water. The dissolution rate of drugs from the ground mixtures was shown to be higher than that of the ground drug, crystalline drug or physical mixture, while the dissolution rate of the inclusion complex was the very highest. Physicochemical stability of the ground mixtures stored under 40°C and 75% RH condition was measured by differential scanning calorimetry. In the case of diazepam, indomethacin, warfarin or hydrocortisone acetate and 3-cyclodextrin ground mixture, drug was crystallized and the crystallinities increased with the increase of storage time, which reached an equilibrium state after 15 days storage. Whereas, acetaminophen-3-cyclodextrin ground mixture was still amorphous during 60 days storage.