Utah-Inha DDS and Advanced Therapeutics, Incheon, Korea.
Arch Pharm Res. 2010 Nov;33(11):1835-42. doi: 10.1007/s12272-010-1116-2. Epub 2010 Nov 30.
The objective of this work was to suggest the biowaiver potential of biopharmaceutical classification system (BCS) Class II drugs in self-microemulsifying drug delivery systems (SMEDDS) which are known to increase the solubility, dissolution and oral absorption of water-insoluble drugs. Cyclosporine was selected as a representative BCS Class II drug. New generic candidate of cyclosporine SMEDDS (test) was applied for the study with brand SMEDDS (reference I) and cyclosporine self-emulsifying drug delivery systems (SEDDS, reference II). Solubility and dissolution of cyclosporine from SMEDDS were critically enhanced, which were the similar behaviors with BCS class I drug. The test showed the identical dissolution rate and the equivalent bioavailability (0.34, 0.42 and 0.68 of p values for AUC₀(→)₂₄(h), C(max) and T(max), respectively) with the reference I. Based on the results, level A in vitro-in vivo correlation (IVIVC) was established from these two SMEDDS formulations. This study serves as a good example for speculating the biowaiver extension potential of BCS Class II drugs specifically in solubilizing formulation such as SMEDDS.
本工作旨在提出生物药剂分类系统（BCS）Ⅱ类药物在自微乳药物传递系统（SMEDDS）中的生物豁免潜力，因为众所周知，SMEDDS 能够提高水不溶性药物的溶解度、溶解速率和口服吸收度。环孢素被选为 BCS Ⅱ类药物的代表。新的通用候选环孢素 SMEDDS（测试）与品牌 SMEDDS（参比 I）和环孢素自乳化药物传递系统（SEDDS，参比 II）一起应用于本研究。SMEDDS 中环孢素的溶解度和溶解速率得到显著提高，这与 BCS Ⅰ类药物的行为相似。测试结果显示，与参比 I 相比，测试具有相同的溶出速率和等效生物利用度（AUC₀(→)₂₄(h)、C(max)和 T(max)的 p 值分别为 0.34、0.42 和 0.68）。基于这些结果，从这两种 SMEDDS 制剂中建立了 A 级体外-体内相关性（IVIVC）。本研究为推测 BCS Ⅱ类药物在特定增溶制剂（如 SMEDDS）中的生物豁免扩展潜力提供了一个很好的范例。
