Rama Prasad Y V, Eaimtrakarn Sudarat, Ishida Makoto, Kusawake Yoichi, Tawa Riichi, Yoshikawa Yukako, Shibata Nobuhito, Takada Kanji
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan.
Int J Pharm. 2003 Dec 11;268(1-2):13-21. doi: 10.1016/j.ijpharm.2003.08.008.
Gentamicin (GM) is a polarized water-soluble compound having very poor intestinal membrane permeability resulting in low oral bioavailability. Labrasol was found to improve the intestinal absorption of GM in rats. In the present study, GM formulations containing labrasol were evaluated in beagle dogs after filling into hydroxypropylmethyl cellulose (HPMC) capsules wrapped with Eudragit L100 (Eud L) and Eudragit S100 (Eud S) films. The results of the in vitro drug release studies could not differentiate between two kinds of enteric capsules and among the three kinds of GM formulations. Oral administration of GM solution at a dose of 50.0 mg per dog of GM and 0.60 ml per dog of labrasol has resulted in Cmax values of 2.38 +/- 0.50 microg/ml and 2.30 +/- 0.42 microg/ml with Eud L and Eud S capsules, respectively. The AUC values obtained were also higher at 4.35 +/- 1.31 microg h/ml and 5.34 +/- 0.95 microg h/ml with Eud L and Eud S capsules, respectively. Formulation of GM as a suspension in labrasol has resulted in the decrease of Cmax values by two to four times and AUC values by > 2.5 times compared to the solution formulation. The above results indicate that solution formulation was better over the suspension. An absorbent, synthetic sponge was used to absorb GM solution formulation and encapsulated with Eud L and Eud S capsules. The Cmax and AUC values obtained with sponge formulation were higher than those of suspension formulations but were lower than solution formulations. There was no significant difference in the extent of GM absorption between Eud L and Eud S capsules used for encapsulating GM formulations.
庆大霉素（GM）是一种极性水溶性化合物，肠道膜通透性很差，导致口服生物利用度低。发现Labrasol可改善大鼠肠道对GM的吸收。在本研究中，将含有Labrasol的GM制剂填充到用Eudragit L100（Eud L）和Eudragit S100（Eud S）薄膜包裹的羟丙基甲基纤维素（HPMC）胶囊中后，在比格犬中进行了评估。体外药物释放研究结果无法区分两种肠溶胶囊以及三种GM制剂。以每只犬50.0 mg GM和每只犬0.60 ml Labrasol的剂量口服GM溶液，使用Eud L和Eud S胶囊时的Cmax值分别为2.38±0.50 μg/ml和2.30±0.42 μg/ml。获得的AUC值也更高，使用Eud L和Eud S胶囊时分别为4.35±1.31 μg h/ml和5.34±0.95 μg h/ml。与溶液制剂相比，将GM制成Labrasol中的混悬液导致Cmax值降低两到四倍，AUC值降低超过2.5倍。上述结果表明溶液制剂优于混悬液制剂。使用一种吸收性合成海绵吸收GM溶液制剂，并用Eud L和Eud S胶囊包封。海绵制剂获得的Cmax和AUC值高于混悬液制剂，但低于溶液制剂。用于包封GM制剂的Eud L和Eud S胶囊在GM吸收程度上没有显著差异。
