In Vivo and Ex Vivo Evaluation of a Multi-Particulate Composite Construct for Sustained Transbuccal Delivery of Carbamazepine

Carbamazepine (CBZ) is a leading molecule in the management of epilepsy. Surveys have revealed that a sufficient lack of therapeutically efficient CBZ transbuccal formulation exists. Therefore, this investigation was directed toward designing multiparticulate composite construct (MCC) for the transbuccal delivery of CBZ. The MCC was formulated using interphase, coparticulate-cosolvent homogenization technique, and lyophilization. In vitro, ex vivo, and in vivo investigations were performed. The mesoporous (pore width = 80.1233 Å) MCC was mechanically stable (ЄD = 0.0290 J, MF = 8.5490 N/mm) and resilient (MR = 5.5040%). It demonstrated distinctive controlled release (9.9800%/h), permeation enhancing (10.8730%/h), drug loading (90.0541%), and bioadhesive (ωadh = 0.0034 J, Fdet = 1.0751 N) capacities. In vivo studies on pigs showed the ability of the MCC to effectively initiate and regulate transbuccal permeation of CBZ as visualized by outcomes of the quantitative and qualitative assessments of isolated plasma samples. Furthermore, comparisons of in vitro and in vivo data of MCC with a conventional product highlighted its capability to attain higher bioavailability and more controlled release trends. Histological and cytological investigations confirmed that the MCC is biocompatible. The mathematical model produced relevant pharmacokinetics and in vitro/in vivo correlation information. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1157-1169, 2014