Kondo N, Iwao T, Hirai K, Fukuda M, Yamanouchi K, Yokoyama K, Miyaji M, Ishihara Y, Kon K, Ogawa Y
Research Division, Green Cross Corp., Osaka, Japan.
J Pharm Sci. 1994 Apr;83(4):566-70. doi: 10.1002/jps.2600830425.
An anticancer agent, N-[[[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]amino]carbonyl]-2 - nitrobenzamide (HO-221, 1), shows poor oral absorption and is only slightly soluble in water (0.055 microgram/mL at 37 degrees C). The coprecipitates with polyvinylpyrrolidone or a vinylpyrrolidone and vinylacetate copolymer (copolyvidone) showed a marked increase of the dissolution rate and attainment of temporary supersaturation of 1. The oral bioavailability of these preparations in dogs at a dose of 1 of 5 mg/kg was approximately 60%, which was 3.5 times greater than that of a micronized preparation. Further, the enteric coprecipitate with hydroxypropyl methylcellulose phthalate 200731, which showed a dissolution profile similar to that of the copolyvidone preparation at pH 6.5 but no dissolution at pH 1.2, revealed the almost complete oral absorption. Because intraduodenal administration of the copolyvidone coprecipitate showed a higher absorption than that of per oral administration, it was suggested that the partial precipitation of crystallites in the nonenteric coprecipitates occurred before reaching the absorption site, the small intestine.
一种抗癌剂，N-[[[4-(5-溴-2-嘧啶氧基)-3-氯苯基]氨基]羰基]-2-硝基苯甲酰胺（HO-221，1），口服吸收差，在水中溶解度仅微溶（37℃时为0.055微克/毫升）。与聚乙烯吡咯烷酮或乙烯基吡咯烷酮和醋酸乙烯酯共聚物（共聚维酮）的共沉淀物显示溶出速率显著增加，并实现了1的暂时过饱和。这些制剂在犬体内以5毫克/千克的剂量给药时的口服生物利用度约为60%，比微粉化制剂高3.5倍。此外，与邻苯二甲酸羟丙基甲基纤维素200731形成的肠溶共沉淀物，在pH 6.5时显示出与共聚维酮制剂相似的溶出曲线，但在pH 1.2时不溶出，显示出几乎完全的口服吸收。由于十二指肠内给予共聚维酮共沉淀物显示出比口服给药更高的吸收，因此提示非肠溶共沉淀物中的微晶在到达吸收部位小肠之前发生了部分沉淀。
