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Influence of Poloxamer on the Dissolution and Stability of Hot-Melt Extrusion–Based Amorphous Solid Dispersions Using Design of Experiments

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  • Advancements in Amorphous Solid Dispersions to Improve Bioavailability
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Abstract

The current study aimed to see the effects of poloxamer P407 on the dissolution performance of hydroxypropyl methylcellulose acetate succinate (AquaSolve™ HPMC-AS HG)-based amorphous solid dispersions (ASD). A weakly acidic, poorly water-soluble active pharmaceutical ingredient (API), mefenamic acid (MA), was selected as a model drug. Thermal investigations, including thermogravimetry (TG) and differential scanning calorimetry (DSC), were conducted for raw materials and physical mixtures as a part of the pre-formulation studies and later to characterize the extruded filaments. The API was blended with the polymers using a twin shell V-blender for 10 min and then extruded using an 11-mm twin-screw co-rotating extruder. Scanning electron microscopy (SEM) was used to study the morphology of the extruded filaments. Furthermore, Fourier-transform infrared spectroscopy (FT-IR) was performed to check the intermolecular interactions of the components. Finally, to assess the in vitro drug release of the ASDs, dissolution testing was conducted in phosphate buffer (0.1 M, pH 7.4) and hydrochloric acid–potassium chloride (HCl-KCl) buffer (0.1 M, pH 1.2). The DSC studies confirmed the formation of the ASDs, and the drug content of the extruded filaments was observed to be within an acceptable range. Furthermore, the study concluded that the formulations containing poloxamer P407 exhibited a significant increase in dissolution performance compared to the filaments with only HPMC-AS HG (at pH 7.4). In addition, the optimized formulation, F3, was stable for over 3 months when exposed to accelerated stability studies.

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Acknowledgements

The authors thank the BASF Corporation, Gattefosse, and Ashland Pharmaceuticals for providing the polymers. The scanning electron microscopy images presented in this work were generated using the instruments and services at the Microscopy and Imaging Center, The University of Mississippi.

Funding

The Microscopy and Imaging Center facility is partly supported by grant 1726880 from the National. Science Foundation.

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Authors and Affiliations

  1. Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, 38677, Mississippi, USA

    Ashay Shukla, Nagi Reddy Dumpa, Rishi Thakkar, Abhishek Shettar, Eman Ashour, Suresh Bandari & Michael A. Repka

  2. Pii Center for Pharmaceutical Technology, The University of Mississippi, University, 38677, Mississippi, USA

    Michael A. Repka

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Contributions

Conceptualization: Ashay Shukla, Suresh Bandari, and Michael A Repka; methodology: Ashay Shukla, Nagi Reddy Dumpa; formal analysis and investigation: Ashay Shukla, Eman Ashour, and Suresh Bandari; writing—original draft preparation: Ashay Shukla; writing—review and editing: Ashay Shukla, Rishi Thakkar, and Abhishek Shettar; supervision and advise: Michael A Repka.

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Correspondence to Michael A. Repka.

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Shukla, A., Dumpa, N.R., Thakkar, R. et al. Influence of Poloxamer on the Dissolution and Stability of Hot-Melt Extrusion–Based Amorphous Solid Dispersions Using Design of Experiments. AAPS PharmSciTech 24, 107 (2023). https://doi.org/10.1208/s12249-023-02562-3

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