Orodispersible Carbamazepine/Hydroxypropyl-β-Cyclodextrin Tablets Obtained by Direct Compression with Five-in-One Co-processed Excipients

March 24, 2020

Title

Orodispersible Carbamazepine/Hydroxypropyl-β-Cyclodextrin Tablets Obtained by Direct Compression with Five-in-One Co-processed Excipients

Author

Jaime Conceição, Oluwatomide Adeoye, Helena Cabral-Marques, Angel Concheiro, Carmen Alvarez-Lorenzo, José Manuel Sousa Lobo

Year

2020

Journal

AAPS PharmaSciTech

Abstract

The development of orodispersible tablets (ODTs) for poorly soluble and poorly flowable drugs via direct compression is still a challenge. This work aimed to develop ODTs of poorly soluble drugs by combining cyclodextrins that form inclusion complexes to improve wetting and release properties, and directly compressible co-processed excipients able to promote rapid disintegration and solve the poor flowability typical of inclusion complexes. Carbamazepine (CBZ) and hydroxypropyl-β-cyclodextrin (HPβCD) were used, respectively, as a model of a poorly soluble drug with poor flowability and as a solubilizing agent. Specifically, CBZ—an antiepileptic and anticonvulsant drug—may benefit from the studied formulation approach, since some patients have swallowing difficulties or fear of choking and are non-cooperative. Prosolv® ODT G2 and F-Melt® type C were the studied five-in-one co-processed excipients. The complex was prepared by kneading. Flow properties of all materials and main properties of the tablets were characterized. The obtained results showed that ODTs containing CBZ/HPβCD complex can be prepared by direct compression through the addition of co-processed excipients. The simultaneous use of co-processing and cyclodextrin technologies rendered ODTs with an in vitro disintegration time in accordance with the European Pharmacopoeia requirement and with a fast and complete drug dissolution. In conclusion, the combination of five-in-one co-processed excipients and hydrophilic cyclodextrins may help addressing the ODT formulation of poorly soluble drugs with poor flowability, by direct compression and with desired release properties.

Instrument

V-650

Keywords

Absorption, Quantitation, Pharmaceutical