The influence of hydrogen bonding between different crystallization tendency drugs and PVPVA on the stability of amorphous solid dispersions

Jingya Wu; Guy Van den Mooter

doi:10.1016/j.ijpharm.2023.123440

The influence of hydrogen bonding between different crystallization tendency drugs and PVPVA on the stability of amorphous solid dispersions

Int J Pharm. 2023 Nov 5:646:123440. doi: 10.1016/j.ijpharm.2023.123440. Epub 2023 Sep 22.

Authors

Jingya Wu¹, Guy Van den Mooter²

Affiliations

¹ Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000 Leuven, Belgium.
² Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000 Leuven, Belgium. Electronic address: guy.vandenmooter@kuleuven.be.

PMID: 37742824
DOI: 10.1016/j.ijpharm.2023.123440

Abstract

Amorphous solid dispersion (ASD) is one of the formulation strategies for drugs displaying low solubility and low oral bioavailability. In this study, high drug-loaded ASDs of drugs with different crystallization tendencies were prepared by spray drying. The aim was to investigate the influence of hydrogen bonding between the drug and the model polymer PVPVA on the physical stability of ASDs containing drugs with different crystallization tendencies. From the 60-day stability study results, the intermolecular hydrogen bonding has a considerable stabilizing effect on the ASDs of the drug with a moderate crystallization tendency. Nimesulide (hydrogen bond donor) can maintain the amorphous form for a longer time than Fenofibrate (no-hydrogen bond donor) during storage. In the ASDs with fast crystallization tendency drugs (naproxen and caffeine), intermolecular hydrogen bonds are not very effective in preventing drug crystallization, and the effect on the stability of ASD is relatively weak. However, for drugs with a slow tendency to crystallize (indomethacin and miconazole), the ASDs remained in an amorphous state during the monitored storage period, making it impossible to compare the effect of intermolecular hydrogen bonds on the stability of this type of ASDs. It also reveals that intermolecular hydrogen bonds can increase the drug loading capacity of ASDs. The relationship between drug loading and ASD stability was further analyzed by the state diagram. This study clearly pointed out that the physical stability of ASDs of drugs with different crystallization tendencies is affected to a different extent by intermolecular hydrogen bonds.

Keywords: Amorphous solid dispersion (ASD); Crystallization tendency; Hydrogen bonding; Long-term stability; Spray drying.