The Dissolution Characteristics of Two Clinically Different Brands of Chlorpromazine HCL Tablets

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Abstract
The time required for 60 percent of the active ingredient in two clinically different brands of chlorpromazine HCl tablets (the T60% value) to be released was found to be 5.7 and 35.4 minutes. The dissolution characteristics of these two products were determined by using the U.S.P. dissolution apparatus, 900 ml of Simulated Gastric Fluid U.S.P. (without enzyme), and a basket-stirrer speed of 50 rpm. The data obtained for these two products indicated that, if the apparatus is carefully standardized, the U.S.P. method yields reproducible results. However, mesh size of basket, depth of the basket-stirrer assembly in the dissolution container, and stirrer speed will alter dissolution profiles. The effects of these variables on dissolution characteristics are well documented in the literature and the data herein merely substantiates the need to carefully standardize operating conditions. On the basis of the results obtained for the two clinically different brands of chlorpromazine HCl tablets, a maximum T60% values of 30 minutes for products containing this drug does not appear to be unreasonable. The T60% value for Brand A is 35.4 ± 3.49 minutes. It would appear, therefore, that a value of 30 minutes might be a suitable time for inclusion in the pharmacopeia. If such a T value were acceptable, four of a total number of seven brands tested in this laboratory would fail to meet the specification. If, on the other hand, the maximum permitted time was 40 minutes, six of the seven brands would comply. The T60% value of the seventh product is in excess of 70 minutes. Over and beyond the clinical evidence available, it is possible to manufacture a product which will rapidly release its drug content to SGF. There, therefore, is both direct and indirect evidence that a 30 minute T60% value is not unreasonable and might be considered by pharmacopeial officials for inclusion in the monograph for this product. Many researchers have criticized the dissolution procedures now described in both the U.S.P. and the N.F. On the basis of the results obtained in this investigation, the most important factor, with respect to the dissolution characteristics of these products, is the dissolution medium. In spite of the fact that chlorpromazine HCl is very soluble in water, it is not a suitable solvent for the determination of dissolution characteristics. There is no evidence that container size or geometry adversely affects dissolution characteristics but there is evidence that T values decrease when a 10 mesh basket is used. This basket effect appears to be product related. For example, a fast dissolving tablet is not affected significantly by mesh size of basket. However, Brand A (and C) are so affected. This would imply that the pharmaceutical properties of these products are such that dissolution characteristics will change if a 10 mesh basket is used in the determination. On the basis of the data reported herein, the U.S.P. dissolution apparatus will yield reproducibile results. With respect to chlorpromazine HCl tablets, if the apparatus is carefully standarized, the stirrer rotated at 50 rpm, and SGF is used as the dissolution medium, T60% values greater than 30 minutes may well indicate that the tested product will be clinically different from those with shorter T60% values.

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