Biowaiver extension potential and IVIVC for BCS Class II drugs by formulation design: Case study for cyclosporine self-microemulsifying formulation.
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.
Utah-Inha DDS and Advanced Therapeutics, Incheon, Korea. Sugeun.Yang@Inha.ac.kr
Su-Geun
SG
Yang
D000042:Absorption; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D004285:Dogs; D016503:Drug Delivery Systems; D015195:Drug Design; D016568:Drugs, Generic / Q000008:administration & dosage / Q000737:chemistry / Q000145:classification* / Q000493:pharmacokinetics; D045703:Emulsifying Agents; D004655:Emulsions; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000145:classification*; D012995:Solubility
D016568:Drugs, Generic; D045703:Emulsifying Agents; D004655:Emulsions; D007166:Immunosuppressive Agents; D004364:Pharmaceutical Preparations; D016572:Cyclosporine