TY - JOUR
T1 - Bioavailability improvement of carbamazepine via oral administration of modified-release amorphous solid dispersions in rats
AU - Li, Houli
AU - Zhang, Meimei
AU - Xiong, Lilong
AU - Feng, Weiyi
AU - Williams, Robert O.
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11
Y1 - 2020/11
N2 - 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 filmfreezing (TFF) process. Three types ofCBZ-mr-ASDwith immediate-, delayed-, and controlled-release propertieswere successfully preparedwithHPMCE3 (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 methodwas used to prepareCBZ-mr-ASDcapsule formulations. Various characterization techniqueswere 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 itsmain activemetabolite carbamazepine 10,11-epoxide (CBZ-E).
AB - 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 filmfreezing (TFF) process. Three types ofCBZ-mr-ASDwith immediate-, delayed-, and controlled-release propertieswere successfully preparedwithHPMCE3 (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 methodwas used to prepareCBZ-mr-ASDcapsule formulations. Various characterization techniqueswere 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 itsmain activemetabolite carbamazepine 10,11-epoxide (CBZ-E).
KW - Amorphous solid dispersions
KW - Bioavailability
KW - Carbamazepine
KW - Modified-release
KW - Oral administration
KW - Thin film freezing
UR - https://www.scopus.com/pages/publications/85094894393
U2 - 10.3390/pharmaceutics12111023
DO - 10.3390/pharmaceutics12111023
M3 - 文章
AN - SCOPUS:85094894393
SN - 1999-4923
VL - 12
SP - 1
EP - 16
JO - Pharmaceutics
JF - Pharmaceutics
IS - 11
M1 - 1023
ER -