Higashi K, Matsushita M, Morisaki K, Hayashi S, Mayumi T
Research and Development Div., Rohto Pharmaceutical Co., Ltd., Osaka, Japan.
J Pharmacobiodyn. 1991 Feb;14(2):72-81. doi: 10.1248/bpb1978.14.72.
Filmy local drug delivery systems (LDDSs) were administered to periodontal pockets in beagles with induced periodontitis, and the in vivo-in vitro correlation of drug release from the LDDS and changes in the clindamycin (CLDM) concentration in the periodontal pocket fluid were studied. The in vitro drug release rate from the LDDS was determined by the dissolution study, without agitation, using phosphate buffer as the dissolution medium at 37 degrees C, and the in vivo drug release rate was determined according to the decrease in the drug load remaining in the LDDS after administration in periodontal pockets. The in vivo drug release rate from LDDSs was lower than the in vitro rate determined by the dissolution study, but the two rates showed a correlation in LDDSs that released drugs by diffusion. Therefore, the in vivo drug release rate was considered to be estimated from the results of the in vitro dissolution study. Changes in the drug concentration in the periodontal pocket fluid after administration of LDDS were dependent on the drug release properties of the LDDS. Also, when CLDM was administered as an aqueous solution in periodontal pockets, its concentration in the periodontal pocket fluid decreased according to a pseudo first-order equation. Therefore, the concentration in the periodontal pocket fluid after administration of a LDDS is considered to be simulated by the one compartment model based on a pseudo first-order elimination process.
将薄膜型局部给药系统（LDDSs）应用于诱导性牙周炎的比格犬牙周袋，并研究了LDDSs药物释放的体内-体外相关性以及牙周袋液中克林霉素（CLDM）浓度的变化。通过溶出度研究确定LDDSs的体外药物释放速率，在37℃下以磷酸盐缓冲液作为溶出介质，不进行搅拌，体内药物释放速率根据给药后LDDSs中剩余药物负荷的减少来确定。LDDSs的体内药物释放速率低于溶出度研究确定的体外速率，但在通过扩散释放药物的LDDSs中，这两个速率显示出相关性。因此，认为可以根据体外溶出度研究的结果来估算体内药物释放速率。LDDSs给药后牙周袋液中药物浓度的变化取决于LDDSs的药物释放特性。此外，当在牙周袋中以水溶液形式给药CLDM时，其在牙周袋液中的浓度根据伪一级方程降低。因此，认为基于伪一级消除过程的一室模型可以模拟LDDSs给药后牙周袋液中的浓度。
