Bioavailability Improvement of Carbamazepine via Oral Administration of Modified-Release Amorphous Solid Dispersions in Rats

• Main Authors: Houli Li (Author), Meimei Zhang (Author), Lilong Xiong (Author), Weiyi Feng (Author), Robert O. Williams (Author)
• Format: Book
• Published: MDPI AG, 2020-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics12111023; 1999-4923
• Keywords: carbamazepine; amorphous solid dispersions; modified-release; oral administration; bioavailability; thin film freezing; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 12, Iss 11, p 1023 (2020)

The purpose of this study was to improve the bioavailability of carbamazepine (CBZ), a poorly water-soluble antiepileptic drug, via modified-release amorphous solid dispersions (mr-ASD) by a thin film freezing (TFF) process. Three types of CBZ-mr-ASD with immediate-, delayed-, and controlled-release properties were successfully prepared with HPMC E3 (hydrophilic), L100-55 (enteric), and cellulose acetate (CA, lipophilic), defined as CBZ-ir-ASD, CBZ-dr-ASD, and CBZ-cr-ASD, respectively. A dry granulation method was used to prepare CBZ-mr-ASD capsule formulations. Various characterization techniques were applied to evaluate the physicochemical properties of CBZ-mr-ASD and the related capsules. The drug remained in an amorphous state when encapsulated within CBZ-mr-ASD, and the capsule formulation progress did not affect the performance of the dispersions. In dissolution tests, the preparations and the corresponding dosage forms similarly showed typical immediate-, delayed-, and controlled-release properties depending on the solubility of the polymers. Moreover, single-dose 24 h pharmacokinetic studies in rats indicated that CBZ-mr-ASD significantly enhanced the oral absorption of CBZ compared to that of crude CBZ. Increased oral absorption of CBZ was observed, especially in the CBZ-dr-ASD formulation, which showed a better pharmacokinetic profile than that of crude CBZ with 2.63- and 3.17-fold improved bioavailability of the drug and its main active metabolite carbamazepine 10,11-epoxide (CBZ-E).