Adi-Dako Ofosua, Ofori-Kwakye Kwabena, Amponsah Seth Kwabena, Boamah Isaac, Kuntworbe Noble, Oppong Esther Eshun
Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.
Department of Pharmaceutics and Microbiology, University of Ghana School of Pharmacy, Accra, Ghana.
J Drug Deliv. 2018 Oct 8;2018:9825363. doi: 10.1155/2018/9825363. eCollection 2018.
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 (C) 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 (T), 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.
评估了可可豆荚壳（CPH）果胶基缓释（MR）胶囊作为氢化可的松在Sprague-Dawley大鼠体内定时释放载体的潜力。将与氯化钙交联的即配CPH果胶基氢化可的松（10毫克）胶囊（制剂A）或锌（制剂B）以及市售速释氢化可的松制剂口服给予Sprague-Dawley大鼠，并使用非房室分析评估药代动力学参数。制剂A有2小时的延迟期，随后治疗大鼠的血清药物浓度升高。胶囊A和B分别在6±0.23小时和6±0.35小时（T）后达到峰值浓度（C），分别为21.799±1.993纳克/毫升和20.844±2.661纳克/毫升。速释制剂在1±0.2小时内达到峰值浓度15.322±0.313纳克/毫升。CPH果胶基胶囊A和B的相对生物利用度分别为213%和274%。制剂A和B的半衰期是速释制剂的三倍多。与市售速释制剂相比，MR胶囊在皮质醇释放方面表现出更高的暴露量、更大的生物利用度和多功能性。此外，MR胶囊表现出药物缓释，夜间皮质醇升高，清晨皮质醇达到峰值，在肾上腺功能不全的管理方面具有前景。
