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

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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.

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Data Availability

Data will be made available on request.

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Funding

This work was supported by the National Natural Science Foundation of China (82373824, 82104401, 82274217, 82204636), the Natural Science Foundation of Jiangsu Province (SBK2020042291), “Double First-Class” University Project (3342100010, 2632021ZD15).

Author information

Author notes

  1. Lingwu Chen and Enshi Hu contributed equally in the experimental works.

Authors and Affiliations

  1. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China

    Lingwu Chen, Shuai Qian, Weili Heng, Yuan Gao & Yuanfeng Wei

  2. Jiuhua & Huayuan Pharmaceutical Co., Ltd, Chuzhou, 239000, People’s Republic of China

    Lingwu Chen

  3. School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China

    Enshi Hu, Peiya Shen & Jianjun Zhang

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  1. Lingwu Chen
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Contributions

Lingwu Chen: Conceptualization, Data curation, Writing—Original Draft. Enshi Hu: Methodology, Data curation, Writing—Original draft. Peiya Shen: Methodology, Formal analysis, Investigation. Shuai Qian: Investigation, Visualization, Validation. Weili Heng: Project administration, Funding acquisition. Jianjun Zhang: Validation, Funding acquisition. Yuan Gao: Supervision, Writing—Review & Editing. Yuanfeng Wei: Supervision, Writing—Review & Editing, Funding acquisition.

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Correspondence to Jianjun Zhang, Yuan Gao or Yuanfeng Wei.

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Chen, L., Hu, E., Shen, P. et al. Development of Amorphous Solid Dispersion Sustained-Release Formulations with Polymer Composite Matrix-Regulated Stable Release Plateaus. Pharm Res (2024). https://doi.org/10.1007/s11095-024-03709-y

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