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

AAPS PharmSciTech. 2020 Jan 2;21(2):39. doi: 10.1208/s12249-019-1579-5.

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.

Keywords: F-Melt® type C; Prosolv® ODT G2; carbamazepine/hydroxypropyl-β-cyclodextrin complexes; direct compression; orally disintegrating tablets.

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin / chemistry*
  • Anticonvulsants / administration & dosage*
  • Anticonvulsants / chemistry*
  • Calorimetry, Differential Scanning
  • Carbamazepine / administration & dosage*
  • Carbamazepine / chemistry*
  • Drug Compounding
  • Drug Liberation
  • Excipients
  • Tablets
  • X-Ray Diffraction

Substances

  • Anticonvulsants
  • Excipients
  • Tablets
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Carbamazepine