Potential of Cocoa Pod Husk Pectin-Based Modified Release Capsules as a Carrier for Chronodelivery of Hydrocortisone in Sprague-Dawley Rats

摘要

The potential of cocoa pod husk (CPH) pectin-based modified release (MR) capsules as a carrier for chronodelivery of hydrocortisone in Sprague-Dawley rats was assessed. Extemporaneously formulated CPH pectin-based hydrocortisone (10?mg) capsules crosslinked with calcium chloride (Formulation A) or zinc (Formulation B) and a commercial immediate release hydrocortisone formulation were administered orally to Sprague-Dawley rats and the pharmacokinetic parameters were evaluated using noncompartmental analysis. Formulation A had a 2?h lag phase followed by an increase in serum drug concentration in the treated rats. Peak concentrations () of 21.799 ± 1.993?ng/ml and 20.844 ± 2.661?ng/ml were achieved after 6 ± 0.23?h and 6 ± 0.35?h (), respectively, for capsules A and B. The immediate release formulation had a peak concentration of 15.322 ± 0.313?ng/ml within 1 ± 0.2?h. The relative bioavailability of the CPH pectin-based capsules A and B was 213% and 274%, respectively. Formulations A and B had half-lives more than three times that of the immediate release formulation. The MR capsules exhibited a higher exposure, greater bioavailability, and versatility in release of cortisol than the commercial immediate release formulation. Additionally, the MR capsules exhibited an extended drug release with overnight cortisol rise and early morning cortisol peak and hold promise in the management of adrenal insufficiency.