title: Direct compression of chitosan: process and formulation factors to improve powder flow and tablet performance.
abstract: Chitosan is a polymer derived from chitin that is widely available at relatively low cost, but due to compression challenges it has limited application for the production of direct compression tablets. The aim of this study was to use certain process and formulation variables to improve manufacturing of tablets containing chitosan as bulking agent. Chitosan particle size and flow properties were determined, which included bulk density, tapped density, compressibility and moisture uptake. The effect of process variables (i.e. compression force, punch depth, percentage compaction in a novel double fill compression process) and formulation variables (i.e. type of glidant, citric acid, pectin, coating with Eudragit S®) on chitosan tablet performance (i.e. mass variation, tensile strength, dissolution) was investigated. Moisture content of the chitosan powder, particle size and the inclusion of glidants had a pronounced effect on its flow ability. Varying the percentage compaction during the first cycle of a double fill compression process produced chitosan tablets with more acceptable tensile strength and dissolution rate properties. The inclusion of citric acid and pectin into the formulation significantly decreased the dissolution rate of isoniazid from the tablets due to gel formation. Direct compression of chitosan powder into tablets can be significantly improved by the investigated process and formulation variables as well as applying a double fill compression process.
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, 2520, South Africa.
authors.forename: Gerhard M
authors.initials: GM
authors.lastname: Buys
authors.forename: Lissinda H
authors.initials: LH
authors.lastname: du Plessis
authors.forename: Andries F
authors.initials: AF
authors.lastname: Marais
authors.forename: Awie F
authors.initials: AF
authors.lastname: Kotze
authors.forename: Josias H
authors.initials: JH
authors.lastname: Hamman
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D019343:Citric Acid / Q000737:chemistry; D019245:Compressive Strength; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D007538:Isoniazid / Q000737:chemistry; D010316:Particle Size; D010368:Pectins / Q000737:chemistry; D011208:Powders; D012995:Solubility; D013607:Tablets; D013718:Tensile Strength
chemical_list: D000995:Antitubercular Agents; D005079:Excipients; D011208:Powders; D013607:Tablets; D019343:Citric Acid; D010368:Pectins; D048271:Chitosan; D007538:Isoniazid