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Enhanced Oral Bioavailability of Progesterone in Bilosome Formulation: Fabrication, Statistical Optimization, and Pharmacokinetic Study

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Abstract

Progesterone, a female sex steroid hormone, is highly lipophilic, leading to poor oral bioavailability. This study aimed to develop a progesterone bilosome system to enhance its oral bioavailability and retain it longer in the body. Progesterone vesicles were formulated with bile salts by thin film hydration method to prevent enzymatic and bile acid degradation. The Box-Behnken experimental design was used to statistically optimize progesterone bilosomes by checking the effect of phosphatidylcholine, cholesterol, and sodium deoxycholate on vesicle size, zeta potential, and entrapment efficiency. The optimum batch showed 239.5 nm vesicle size, -28.2 mV zeta potential and 84.08% entrapment efficiency, respectively, which were significantly affected by phosphatidylcholine and cholesterol concentration. The successful incorporation of progesterone in the system was evident from ATR-FTIR analysis that revealed no sharp progesterone peaks in bilosomes. TEM analysis confirmed the spherical structure and uniform bilosome vesicles. Furthermore, the in vitro drug release of progesterone bilosomes revealed a sustained pattern exhibiting 90% drug release in 48 h. The pharmacokinetic study in female ovariectomized Wistar rats confirmed the 4.287- and 9.75-fold enhanced oral bioavailability of the progesterone bilosomes than marketed capsules and progesterone API, respectively. Therefore, progesterone bilosome formulation can be further explored for improved oral administration in chronic treatments.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

The authors are grateful to La Chandra Pharma Lab, Ahmedabad, India, for a gift sample of Progesterone. The authors thank VAV Life Sciences Pvt. Ltd, India, for providing a gift sample of Leciva S75.

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Authors and Affiliations

  1. Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra, 400056, India

    Ronak Maheshwari & Sarika Wairkar

  2. SVKM’s Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, Maharashtra, 400056, India

    Lokesh Kumar Bhatt

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  1. Ronak Maheshwari
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  2. Lokesh Kumar Bhatt
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  3. Sarika Wairkar
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RM has done the data collection and drafting of the manuscript. LB was involved in methodology and data analysis. SW conceptualized the manuscript, data analysis, and approval of the final manuscript.

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Correspondence to Sarika Wairkar.

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Maheshwari, R., Bhatt, L. & Wairkar, S. Enhanced Oral Bioavailability of Progesterone in Bilosome Formulation: Fabrication, Statistical Optimization, and Pharmacokinetic Study. AAPS PharmSciTech 25, 29 (2024). https://doi.org/10.1208/s12249-024-02747-4

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