Biopharmaceutical Studies on the Coprecipitate of Metoclopramide-Polyvinylpyrrolidone

Metoclopramide-Polyvinylpyrrolidone 공침물(共沈物)에 관(關)한 생물약제학적(生物藥劑學的) 연구(硏究)

In order to increase the solubility of metoclopramide, various ratio coprecipitates with polyvinylpyrrolidone (M.W. 40,000) were prepared. The experiments of the solubility, physicochemical characteristics were quantitatively developed. The solubility increased as the ratio of rnetoclopramide to polyvinylpyrrolidone in metoclopramide-polyvinylpyrrolindone coprecipitate increased. In powder state, the dissolution rate of metoclopramide-polyvinylpyrrolidone coprecipitate was greater than that of metoclopramide and metoclopramide-polyvinylpyrrolidone physical mixture. Dissolution characteristics of non-disintegrating disk with constant surfacearea was in accord with Noyes-Nernst equation. The intrinsic dissolution rate, G, at $37^{\circ}C$ was $3.98{\times}10^{-7}M/cm^2{\cdot}min$ for metoclopramide, $2.26{\times}10^{-6}\;M/cm^2{\cdot}min$ for 1 : 5 metoclopramide-polyvinylpyrrolidone coprecipitate, respectively. Accordingly, activation energy of metoclopramide was 15,061cal/M, 9,178cal/M for 1 : 5 metoclopramide-polyvinylpyrrolidone coprecipitate and the activation energy decreased as the coprecipitate was formed. X-ray diffraction study revealed the fact that metoclopramide was crystalline, in contrast, there was no crystallinity evident in the 1 : 5 metoclopramide-polyvinylpyrrolidone coprecipitate. There was no difference between physical mixture and coprecipitate in TLC, UV and NMR studies. From the comparision between physical mixture and coprecipitate in IR spectrum, the interaction such as association between metoclopramide and polyvinylpyrrolidone was considered. But the association was easily dissociated in methanol solution.