Development of Amorphous Solid Dispersion Sustained-Release Formulations with Polymer Composite Matrix-Regulated Stable Release Plateaus

Lingwu Chen; Enshi Hu; Peiya Shen; Shuai Qian; Weili Heng; Jianjun Zhang; Yuan Gao; Yuanfeng Wei

doi:10.1007/s11095-024-03709-y

Development of Amorphous Solid Dispersion Sustained-Release Formulations with Polymer Composite Matrix-Regulated Stable Release Plateaus

Pharm Res. 2024 May 14. doi: 10.1007/s11095-024-03709-y. Online ahead of print.

Authors

Lingwu Chen^#^{1

2}, Enshi Hu^#³, Peiya Shen³, Shuai Qian¹, Weili Heng¹, Jianjun Zhang⁴, Yuan Gao⁵, Yuanfeng Wei⁶

Affiliations

¹ School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.
² Jiuhua & Huayuan Pharmaceutical Co., Ltd, Chuzhou, 239000, People's Republic of China.
³ School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.
⁴ School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. myamicute@163.com.
⁵ School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. newgaoyuan@163.com.
⁶ School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China. weiyuanfengyuer@yeah.net.

^# Contributed equally.

PMID: 38744732
DOI: 10.1007/s11095-024-03709-y

Abstract

Purpose: This study was designed to develop ibuprofen (IBU) sustained-release amorphous solid dispersion (ASD) using polymer composites matrix with drug release plateaus for stable release and to further reveal intrinsic links between polymer' matrix ratios and drug release behaviors.

Methods: Hydrophilic polymers and hydrophobic polymers were combined to form different composite matrices in developing IBU ASD formulations by hot melt extrusion technique. The intrinsic links between the mixed polymer matrix ratio and drug dissolution behaviors was deeply clarified from the dissolution curves of hydrophilic polymers and swelling curves of composite matrices, and intermolecular forces among the components in ASDs.

Results: IBU + ammonio methacrylate copolymer type B (RSPO) + poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP VA64) physical mixtures presented unstable release behaviors with large error bars due to inhomogeneities at the micrometer level. However, IBU-RSPO-PVP VA64 ASDs showed a "dissolution plateau phenomenon", i.e., release behaviors of IBU in ASDs were unaffected by polymer ratios when PVP VA64 content was 35% ~ 50%, which could reduce risks of variations in release behaviors due to fluctuations in prescriptions/processes. The release of IBU in ASDs was simultaneously regulated by the PVP VA64-mediated "dissolution" and RSPO-PVP VA64 assembly-mediated "swelling". Radial distribution function suggested that similar intermolecular forces between RSPO and PVP VA64 were key mechanisms for the "dissolution plateau phenomenon" in ASDs at 35% ~ 50% of PVP VA64.

Conclusions: This study provided ideas for developing ASD sustained-release formulations with stable release plateau modulated by polymer combinations, taking full advantages of simple process/prescription, ease of scale-up and favorable release behavior of ASD formulations.

Keywords: amorphous solid dispersion; drug release plateau; hot melt extrusion technology; polymer composite matrix; sustained-release regulation.

Abstract

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