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Enhanced Oral Bioavailability of Chlormadinone Acetate through a Self-Microemulsifying Drug Delivery System for a Potential Dose Reduction

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Abstract

Chlormadinone acetate (CMA) is a derivative of the naturally secreted hormone progesterone and exhibits reliable contraceptive and non-contraceptive benefits. Although the marketed product of CMA as oral tablets under the trade name Belara® has been highly successful, there is still room for further improvements in oral bioavailability and a reduction in the clinical dose to decrease related adverse effects. In the current study, a CMA-based self-microemulsifying drug delivery system (SMEDDS) was developed using 32% ethyl oleate as an oil phase, 40% Tween-80 as a surfactant, and 12% Transcutol P combined with 16% PEG400 as a cosurfactant, resulting in spherical droplets with a z-average particle size of 38.92 nm and an average zeta potential of − 3.18 mv. The in vitro release rate of CMA from CMA-SMEDDS in different media (distilled water, HCl solution at pH 1.2, phosphate buffers at pH 4.5 and pH 6.8) was significantly faster than that from Belara® in the first 15 min. A pharmacokinetic study in rats showed that the Cmax and AUC of CMA-SMEDDS were significantly higher (P < 0.01) than those of Belara®, with a 1.98-fold increase in oral bioavailability. In comparison with Belara®, the developed CMA-SMEDDS showed promising release profiles both in vitro and in vivo, which could potentially be useful in enhancing oral bioavailability and reducing the clinical dose of CMA.

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Acknowledgments

The project was supported by grants from the Scientific Research Project of Shanghai Municipal Health and Family Planning Commission (20154Y0032).

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Authors and Affiliations

  1. Key Laboratory of Contraceptives and Devices Research (NPFPC), Shanghai Engineering Research Center of Reproductive Health Drug and Devices, Shanghai Institute of Planned Parenthood Research, 200032, Shanghai, People’s Republic of China

    Jia Zeng, Jianxing Chen, Liangkang Chen, Wei Zheng, Yunfeng Cao & Ting Huang

Authors
  1. Jia Zeng
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  2. Jianxing Chen
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  3. Liangkang Chen
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  4. Wei Zheng
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  5. Yunfeng Cao
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  6. Ting Huang
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Corresponding author

Correspondence to Ting Huang.

Ethics declarations

All experiments were performed according to the guidelines for the care and use of animals established by the Shanghai Institute of Planned Parenthood Research, which have already been approved by the ethics committee of the Shanghai Institute of Planned Parenthood Research (No. 2015-14).

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The authors declare that they have no conflict of interest.

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Enhanced Oral Bioavailability of CMA by a SMEDDS

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Zeng, J., Chen, J., Chen, L. et al. Enhanced Oral Bioavailability of Chlormadinone Acetate through a Self-Microemulsifying Drug Delivery System for a Potential Dose Reduction. AAPS PharmSciTech 19, 3850–3858 (2018). https://doi.org/10.1208/s12249-018-1193-y

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  • DOI: https://doi.org/10.1208/s12249-018-1193-y

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