Efavirenz pre-formulation study : selection of a cyclodextrin inclusion complex or co-crystal complex for tabletting
type: CreativeWork
description: Efavirenz is a non-nucleoside reverse transcriptase inhibitor used as an anti-retroviral for the treatment of human immunodeficiency virus (HIV) type I. It is classified as a class IΙ drug under the Biopharmaceutical Classification System (BCS) and exhibits a low solubility (aqueous solubility of 9.0 μg/ml) and high permeability (variable oral bioavailability). This study aims to choose a pre-formulation protocol with the best efavirenz derivative in literature between co-crystals and CD inclusion complexes. Upon selection of the efavirenz derivative, the complications of both small scale and large scale laboratory pre-formulation production is highlighted for formulation of a tablet dosage form. Numerous variables were selected for the pre-formulation protocol. Physical, chemical, pharmacological, pharmaceutical and economical variables were investigated. Citric acid monohydrate (CTRC) was chosen as the best co-former for a co-crystal while hydroxypropyl-beta-cyclodextrin (HP-β-CD) was selected as a host for an inclusion complex. Pharmaceutically, the angle of repose, Carr’s index, Hausner’s ratio, moisture content, disintegration time, hardness/resistance to crush, manufacturing process problems and particle size of the CTRC and HP-β-CD were all evaluated. The CTRC was ultimately selected for formulation of a tablet. The preparation of small laboratory scale of EFA/CTRC co-crystal was successfully achieved after several attempts. The large laboratory scale of EFA/CTRC was prepared under various environmental seasons which were indicated as batches 1-6 for purposes of this study. Characterization of the large laboratory scale EFA/CTRC co-crystals was performed by scanning electron microscopy (SEM), hot-stage microscopy (HSM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and by physical inspection (i.e. season, texture, colour, shape and particle size) of the EFA/CTRC product. Batch 1 and 2 were prepared during the summer season. The SEM…
abstract: Efavirenz is a non-nucleoside reverse transcriptase inhibitor used as an anti-retroviral for the treatment of human immunodeficiency virus (HIV) type I. It is classified as a class IΙ drug under the Biopharmaceutical Classification System (BCS) and exhibits a low solubility (aqueous solubility of 9.0 μg/ml) and high permeability (variable oral bioavailability). This study aims to choose a pre-formulation protocol with the best efavirenz derivative in literature between co-crystals and CD inclusion complexes. Upon selection of the efavirenz derivative, the complications of both small scale and large scale laboratory pre-formulation production is highlighted for formulation of a tablet dosage form. Numerous variables were selected for the pre-formulation protocol. Physical, chemical, pharmacological, pharmaceutical and economical variables were investigated. Citric acid monohydrate (CTRC) was chosen as the best co-former for a co-crystal while hydroxypropyl-beta-cyclodextrin (HP-β-CD) was selected as a host for an inclusion complex. Pharmaceutically, the angle of repose, Carr’s index, Hausner’s ratio, moisture content, disintegration time, hardness/resistance to crush, manufacturing process problems and particle size of the CTRC and HP-β-CD were all evaluated. The CTRC was ultimately selected for formulation of a tablet. The preparation of small laboratory scale of EFA/CTRC co-crystal was successfully achieved after several attempts. The large laboratory scale of EFA/CTRC was prepared under various environmental seasons which were indicated as batches 1-6 for purposes of this study. Characterization of the large laboratory scale EFA/CTRC co-crystals was performed by scanning electron microscopy (SEM), hot-stage microscopy (HSM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and by physical inspection (i.e. season, texture, colour, shape and particle size) of the EFA/CTRC product. Batch 1 and 2 were prepared during the summer season. The SEM…
author: Rafieda, Ali Mohamed Omar
keywords: Efavirenz, Co-crystallization, Cyclodextrin inclusion, Scanning electron microscopy, Hot-stage microscopy
license: https://uwcscholar.uwc.ac.za/bitstreams/55478534-32f6-4ed7-b08f-85081f9c0dab/download
date published: 2015
date modified: 2026-07-24T06:00:56Z
provider: University of the Western Cape
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of the Western Cape