Formulation and Evaluation of Colon Targeted Pulsincap Delivery of Carvedilol for Treatment of Hypertension

Abstract

The objective of this work is to ensure the controlled release of carvedilol at a given time and location for treating hypertension as a pulsincap delivery system. The capsule body was made of insoluble hard gelatin and filled with carvedilol microspheres, then a hydrogel plug was used to close it. The microspheres were made by oil/water emulsification followed by a solvent evaporation method in different drug: polymer ratios using Eudragit L100 and S100 as polymers. Direct compression was used to make the hydrogel plugs. Various assessment parameters, FTIR analysis, and in-vitro release experiments were performed on the produced microspheres. The results showed that formulated microspheres had satisfactory results for various micrometric properties. The microsphere formulations showed the highest entrapment efficiency were F9, F14 and F15 (89.18±2.25, 83.91±2.13 and 92.2±2.28% respectively). FTIR results revealed that carvedilol was molecularly dispersed into the polymeric matrix. In-vitro release studies of carvedilol microspheres showed sustained action over 8 hours. The pulsincap system was evaluated for the in-vitro release studies. PF9 had the highest cumulative release after 12 hours (94.161±0.83 %) and reduced drug release during lag time so, PF9 was chosen for the in-vivo study. The in-vivo study was carried out on 16 hypertensive patients using HPLC method to measure carvedilol conc. in the blood and compare PF9 with commercially available tablets of the same strength. The in-vivo study revealed that the prepared pulsincap has shown better pharmacokinetics parameters compared with the marketed formulation with a delayed release pattern for the effective treatment of hypertension.