In vitro and in vivo evaluation of single-unit commercial immediate-and sustained-release capsules compared with multiple-unit polystyrene microparticles dosage forms of indomethacin.
The objective of this study is to select a multiple-unit sustained-release formulation and to compare it with both commercial immediate and single unit sustained-release capsules and also to determine whether an in vitro-in vivo correlation exists for single- and multiple- unit formulations. Indomethacin (20-60% w/w)-loaded, multiple-unit polystyrene microparticles were prepared by emulsion-solvent evaporation method from an aqueous system. The in vitro release profiles obtained in phosphate buffer of pH 6.8 for drug-loaded polystyrene microparticles and for commercial sustained-release capsules (Indocap-SR, 75 mg) were compared. As the microparticles with 50% indomethacin load showed a release profile comparable to that of the Indocap-SR release profile, the microparticles with this drug load was considered as optimized/selected formulation and, therefore, was subjected to stability study and in vivo study in human volunteers. In spite of significantly higher C(max), Ka, and Ke, and lower T(max), t1/2a, t1/2e and AUC(0 --> infinity)) values observed with commercial Microcid immediate-release capsules, there was no sign of difference among the listed parameters between optimized microparticles and Indocap-SR capsules. Indeed, the values of retard quotient (Rdelta) calculated from half-value duration analysis did not show any statistical difference, indicating the occurrence of an almost same degree of retardation of drug release from the optimized microparticles and the Indocap-SR capsules. Furthermore, linear relationship obtained between the percentages dissolved and absorbed suggests a means to predict in vivo absorption by measuring in vitro dissolution. The results suggest that the optimized polystyrene microparticles could provide an alternative controlled-release drug delivery system for indomethacin.
Tamilvanan
Shunmugaperumal
S
Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700 032, India. tamilvanan2k@yahoo.com
Sa
Biswanath
B
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D005544:Forecasting; D006207:Half-Life; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008863:Microspheres; D010316:Particle Size; D011137:Polystyrenes / Q000737:chemistry*; D012995:Solubility
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011137:Polystyrenes; D007213:Indomethacin