Investigation of Hot Melt Extrusion Technique for Formulating Ternary Amorphous Solid Dispersion of Bcs-iv Anti-platelet Drug for Solubility and Dissolution Enhancement
Year: 2025
Type: article
Abstract: Objective: The objective of this study was to investigate Hot Melt Extrusion (HME) technique of formulating stable amorphous solid dispersion of BCS IV drug ticagrelor for dissolution and bioavailability enhancement. Methods: Ticagrelor, a low soluble and low permeable anti-platelet agent has been used as a model drug. A ternary Amorphous Solid Dispersion (ASD) was explored to improve the solubility and dissolution of ticagrelor using amphiphilic polymer Hydroxy Propyl Methyl Cellulose Acetate Succinate (HMPC-AS) and solubilizer poloxamer (Kolliphor RH188) employing HME. The ratio of ternary ASD was optimized by Design of Experiments (DoE) with 32-factor design. The Design Expert®13 was explored for the statistical evaluation. The HME technique was preferred considering solvent free process, scalability and industrial safety. The extent of amorphization of ticagrelor was evaluated by Differential Scanning Calorimetry (DSC) and Powder X-Ray Diffraction (P-XRD). The comparative saturation solubility was evaluated by HPLC method and drug dissolution rate by UV spectroscopy. Results: The ternary ASD prepared by HME technique has shown complete amorphization of input crystalline ticagrelor as confirmed by P-XRD and DSC analysis of ticagrelor solid dispersion formulated with HPMC-AS and poloxamer. The ternary ASD formulation was optimized by DoE has shown significant enhancement in ticagrelor solubility and 8 fold increase in dissolution rate and extent compared to conventional release marketed tablets. Conclusion: A stable tablets formulation of ticagrelor ternary ASD was successfully prepared by HME technique and could enhance in vitro dissolution significantly, to an extent of 8 fold by complete conversion from crystalline to amorphous state.
Authors: RAJESH GIRADKAR, JANAKI DEVI SIRISOLLA
Institution: GITAM University
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4409378795