Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 86, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2023.104696
Keywords
Mechanochemistry; Chitosan grafting; Drug-polymer interactions; 24-dichloro phenoxyacetic acid; Solid dispersion; Amorphization
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Mechanochemistry involves the application of mechanical force to induce chemical changes in the material solid state. In this study, chitosan (CS) was grafted with 2,4-dichlorophenoxyacetic acid (2,4-D) to promote CO2 adsorption. The resulting tablets showed increased tensile strength, sustained drug release, and resistance to disintegration.
Background: Mechanochemistry involves the application of mechanical force to induce chemical changes in the material solid state. Mechanochemistry promises to overcome many drawbacks in pharmaceutical formulation. Chitosan (CS), a semisynthetic polymer obtained by N-deacetylation of chitin, has attracted attention in various biomedical and pharmaceutical applications. Methods: CS was grafted with 2,4-dichlorophenoxyacetic acid (2,4-D), a significantly hydrophobic and safe substituent, to promote facile adsorption of CO2. Physical mixtures and corresponding tablets comprised of model drugs and CS-2,4-D were prepared and characterized by DSC, XRD, and IR, and were compared with pure drugs and their mixtures with unmodified CS. Tensile strength and drug-release profiles of CS-2,4-D tablets were evaluated and compared with counterparts prepared from unmodified CS. Results: Adsorbed CO2 promoted the formation of powerful and extensive carbamate crosslinks within CS-2,4-D upon mechanochemical stress induced by mixing the new polymer with model drugs followed by tableting. Corresponding tablets showed increased tensile strength, sustained drug release and resistance to disintegration over 72 h of exposure to dissolution media. MTT bioassay indicated CS-2,4-D to be less cytotoxic than un-modified CS. Conclusions: the current study provided a proof-of-principle on tableting mediated mechanochemical matrix crosslinking.
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