A Pharmacokinetic Evaluation of a Pectin-Based Oral Multiparticulate Matrix Carrier of Carbamazepine

Abstract

Background. Carbamazepine is a drug used in the treatment of neurological disorders such as epilepsy. However, due to its erratic absorption, oral bioavailability is often poor. There is, therefore, the need to develop alternative formulations for carbamazepine with better pharmacokinetic characteristics. Aim. The aim of this study was to formulate an oral modified-release multiparticulate matrix of carbamazepine from cocoa pod husk (CPH) pectin and evaluate the pharmacokinetic profile of this formulation using in vitro and in vivo models. Methods. CPH pectin was extracted from cocoa pod husks with hot aqueous and citric acid solutions. Oral multiparticulate carbamazepine matrices were formulated from CPH pectin cross-linked with calcium. The formulation was evaluated for carbamazepine content and release profile in vitro. For in vivo pharmacokinetic profile estimation, rats were put into 4 groups of 5 animals each to receive carbamazepine multiparticulate matrix formulations A and B, carbamazepine powder, and Tegretol CR®. Animals in each group received 200 mg/kg of each drug via the oral route. Maximum plasma concentration C max , area under the concentration-time curve (AUC), elimination rate constant K e , and terminal half-life t 1 / 2 of the formulations were estimated by noncompartmental analysis. Results. The pectin extraction from fresh cocoa pod husks using hot aqueous and citric acid solutions gave pectin yields of 9.63% and 11.54%, respectively. The drug content of carbamazepine in CPH pectin formulations A and B was 95% and 96%, respectively. There was controlled and sustained release of carbamazepine for both formulations A and B in vitro. AUC0⟶36 (176.20 ± 7.97 µg.h/mL), C max (8.45 ± 0.71 μg/mL), T max (12 ± 1.28 h), and t 1 / 2 (13.75 ± 3.28 h) of formulation A showed a moderately enhanced and comparable pharmacokinetic profile to Tegretol CR® (AUC0⟶36: 155 ± 7.15 µg.h/mL, C max : 8.24 ± 0.45 μg/mL, T max : 8.0 ± 2.23 h, and t 1 / 2 : 13.51 ± 2.87 h). Conclusion. Findings from the study suggest that formulations of CPH pectin had the potential to control and maintain therapeutic concentrations of carbamazepine in circulation over a period of time in the rat model.

Pectin Extraction from Residues of the Cocoa Fruit (<em>Theobroma cacao</em> L.) by Different Organic Acids: A Comparative Study

“…Due to the above, the yields obtained in the present study are lower than those obtained by similar studies. Thus, for example, pectin yielded of 5.55-7.70 % [9] and 6.10-9.20 % [53] dry wt., and 18.12 % [40], 11.52 % [54], and 9.00 % [55] wet-fresh wt. has been reported elsewhere for extraction with citric acid, while in the present work, a modest 0.62 % wt.…”

Cocoa Pod Husk: A High‐Pectin Source with Applications in the Food and Biomedical Fields

“…Furthermore, the ability of CPH pectin, after acidic and water extraction treatments, was tested to tune the drug release. Amponsah et al [16] described pectin-based multiparticulate matrices prepared by mixing CPH pectin, CaCl 2 , hydroxypropyl methylcellulose and carbamazepine (~100 mg), that is a widely used and poorly water-soluble antiepileptic drug [54]. These products were tested in simulated intestinal conditions (pH 6.8, 37 + 0.5 °C, and 50 rpm) for 8 h, showing an initial burst followed by a slow release of drug indicative of a biphasic release pattern useful for the maintenance of sustained drug concentration.…”

“…Furthermore, applied research shows the great potential of pectin extracted from CPH in the pharmaceutical and biomedical industry, focused on the creation of matrices and excipients. This is due to the suitable assimilation results of the pectin tested in animal in vivo studies, where no biochemical changes, organ damage, presence of bacteria or intoxication are reported [1,[16][17][18]. This review will investigate pectin extracted from CPHs by providing a critical analysis of the advantages and limitations of the current extraction methodologies, new perspectives in its characterization, and usage in different fields ranging from food to biomedical applications.…”

“…Furthermore, applied research shows the great potential of pectin extracted from CPH in the pharmaceutical and biomedical industry, focused on the creation of matrices and excipients. This is due to the suitable assimilation results of the pectin tested in animal in vivo studies, where no biochemical changes, organ damage, presence of bacteria or intoxication are reported 1, 16–18.…”

Advancement of Nanofibrous Mats and Common Useful Drug Delivery Applications

“…The practice of drug administration has evolved dramatically over the last few decades. In the field of drug delivery, the ultimate goal is to exclusively direct therapeutic agents to pathological tissues in order to increase therapeutic efficacy and eliminate side effects [ 10 , 11 ]. Researchers understand more about the different ways our bodies respond to illness and the impact of specific environmental or genetic cues as they study how diseases develop and progress.…”