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Viability of Lactobacillus acidophilus in Thin-Film Freeze-Dried Powders Filled in Delayed-Release Vegetarian Capsules in a Simulated Gastric Fluid

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Abstract

Previously, we have shown that thin-film freeze-drying can be applied to prepare dry powders of bacteria such as Lactobacillus acidophilus. Herein, we tested the viability of L. acidophilus in thin-film freeze-dried powders (TFF powders) filled in delayed-release vegetarian capsules in a simulated gastric fluid (SGF) consisting of 0.1N hydrochloric acid and sodium chloride. Initially, we determined the water removal rate from frozen thin films on relatively larger scales (i.e., 10–750 g). We then prepared and characterized two TFF powders of L. acidophilus with either sucrose and maltodextrin or sucrose and hydroxypropyl methylcellulose acetate succinate (HPMC-AS), a pH-sensitive polymer, as excipients and evaluated the viability of the bacteria after the TFF powders were filled in delayed-release vegetarian capsules and the capsules were incubated in the SGF for 30 min. On 10–750 g scales and at the settings specified, water removal from frozen thin films was faster than from slow shelf-frozen bulk solids. When the L. acidophilus in sucrose and HPMC-AS TFF powder was filled into a delayed-release capsule that was placed into another delayed-release capsule, the bacterial viability reduction after incubation in the SGF can be minimized to within 1 log in colony forming unit (CFU). However, for the L. acidophilus in sucrose and maltodextrin TFF powder, even in the capsule-in-capsule dosage form, bacterial CFU reduction was > 2 logs. TFF powders of live microorganisms containing an acid-resistant material in capsule-in-capsule delayed-release vegetarian capsules have the potential for oral delivery of those microorganisms.

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Acknowledgements

We would like to thank Anita Solanki from ACG Associated Capsules (Canada) Ltd and Jnanadeva Bhat and Manali Dalvi from ACG Scitech Centre (Mumbai, India) for their help. We would also like to thank Angela Ren from the College of Pharmacy at UT Austin for facilitating side-by-side diffusion cell experiments.

Funding

This work was supported in part by TFF Pharmaceuticals, Inc. We also thank ACG North America, LLC. for its generous gift for graduate education.

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Authors and Affiliations

  1. Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA

    Jie-Liang Wang, Benjamin Southard, Miguel O. Jara, Yu-Sheng Yu, Haiyue Xu, Robert O. Williams III & Zhengrong Cui

  2. Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan

    Yu-Sheng Yu

  3. ACG North America, LLC, Piscataway, New Jersey, USA

    Justin Kalafat

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  1. Jie-Liang Wang
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Contributions

Jie-Liang Wang: conceptualization, writing—original draft preparation, literature search, data acquisition and analysis. Benjamin Southard: conceptualization, review, editing, literature search, data acquisition. Miguel O. Jara: conceptualization and data acquisition. Yu-Sheng Yu: data acquisition and analysis. Haiyue Xu: conceptualization and review. Justin Kalafat: conceptualization and review. Robert O. Williams III and Zhengrong Cui: review, editing, guidance, supervision, resources and funding, and conceptualization.

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Correspondence to Robert O. Williams III or Zhengrong Cui.

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ROW and ZC report financial support provided by TFF Pharmaceuticals, Inc. ZC reports a relationship with TFF Pharmaceuticals, Inc., that includes equity or stocks and funding. ROW reports a relationship with TFF Pharmaceuticals, Inc., that includes consulting or advisory, equity or stocks, and funding. HX reports a relationship with TFF Pharmaceuticals, Inc., that includes consulting or advisory.

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Wang, JL., Southard, B., Jara, M.O. et al. Viability of Lactobacillus acidophilus in Thin-Film Freeze-Dried Powders Filled in Delayed-Release Vegetarian Capsules in a Simulated Gastric Fluid. AAPS PharmSciTech 24, 193 (2023). https://doi.org/10.1208/s12249-023-02644-2

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