Impact of polymer type, ASD loading and polymer-drug ratio on ASD tablet disintegration and drug release

Amorphous solid dispersion (ASD) has become an attractive strategy to enhance solubility and bioavailability of poorly water-soluble drugs. To facilitate oral administration, ASDs are commonly incorporated into tablets. Disintegration and drug release from ASD tablets are thus critical for achieving the inherent solubility advantage of amorphous drugs. In this work, the impact of polymer type, ASD loading in tablet and polymer-drug ratio in ASD on disintegration and drug release of ASD tablets was systematically studied. Two hydrophilic polymers PVPVA and HPMC and one relatively hydrophobic polymer HPMCAS were evaluated. Dissolution testing was performed, and disintegration time was recorded during dissolution testing. As ASD loading increased, tablet disintegration time increased for all three polymer-based ASD tablets, and this effect was more pronounced for hydrophilic polymer-based ASD tablets. As polymer-drug ratio increased, tablet disintegration time increased for hydrophilic polymer-based ASD tablets, however, it remained short and largely unchanged for HPMCAS-based ASD tablets. Consequently, at high ASD loadings or high polymer-drug ratios, HPMCAS-based ASD tablets showed faster drug release than PVPVA- or HPMC-based ASD tablets. These results were attributed to the differences between polymer hydrophilicities and viscosities of polymer aqueous solutions. This work is valuable for understanding the disintegration and drug release of ASD tablets and provides insight to ASD composition selection from downstream tablet formulation perspective. Continue on Impact of polymer type, ASD loading and polymer-drug ratio on ASD tablet disintegration and drug release

Keywords: Amorphous formulation, ASD tablet, disintegration, dissolution, PVPVA (Kollidon VA64), HPMC (Methocel E5 Premium LV), HPMCAS-MF, dichloromethane, methanol, Avicel PH102 (Microcrystalline Cellulose, Lactose Fast Flo 316 croscarmellose sodium, magnesium stearate

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