Impact of Drug–Polymer Intermolecular Interactions on Dissolution Performance of Copovidone-Based Amorphous Solid Dispersions

For poorly soluble drugs formulated as amorphous solid dispersions (ASDs), fast and complete release with the generation of drug-rich colloidal particles is beneficial for optimizing drug absorption. However, this ideal dissolution profile can only be achieved when the drug releases at the same normalized rate as the polymer, also known as congruent release. This phenomenon only occurs when the drug loading (DL) is below a certain value.

The maximal DL at which congruent release occurs is defined as the limit of congruency (LoC). The purpose of this study was to investigate the relationship between drug chemical structure and LoC for PVPVA-based ASDs. The compounds investigated shared a common scaffold substituted with different functional groups, capable of forming hydrogen bonds only, halogen bonds only, both hydrogen and halogen bonds, or nonspecific interactions only with the polymer. Intermolecular interactions were studied and confirmed by X-ray photoelectron spectroscopy and infrared spectroscopy.

The release rates of ASDs with different DLs were investigated using surface area normalized dissolution. ASDs with hydrogen bond formation between the drug and polymer had lower LoCs, while compounds that were only able to form halogen bonds or nonspecific interactions with the polymer achieved considerably higher LoCs. This study highlights the impact of different types of drug–polymer interactions on ASD dissolution performance, providing insights into the role of drug and polymer chemical structures on the LoC and ASD performance in general.

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Article information: Chailu Que, Alexandru Deac, Dmitry Y. Zemlyanov, QingQing Qi, Anura S. Indulkar, Yi Gao, Geoff G. Z. Zhang, and Lynne S. Taylor. Molecular Pharmaceutics. Article ASAP. DOI:10.1021/acs.molpharmaceut.1c00419