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Development and Evaluation of Topical Delivery of Microemulsions Containing Adapalene (MEs-Ap) for Acne

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Abstract

The main objective of the study was to prepare the microemulsions containing adapalene (MEs-Ap) to enhance epidermal penetration, dermal retention, and local bioavailability compared with the commercial preparation. The optimal formulations were selected by solubility experiments, pseudo-ternary phase diagram, and percutaneous permeation experiments and the physiochemical properties were also investigated. Then, the study of permeability, retention, safety, pharmacodynamics, and pharmacokinetics in the skin for MEs-Ap compared with the commercial preparation were researched. The optimized formulation was developed as follows: the ratio of AP, isopropyl myristate, polyoxyethylene hydrogenated castor oil, ethanol, and water was 0.01:1:1.25:3.75:4 (w/w). The globule size and average viscosity of the optimized MEs-Ap were 99.34 nm and 1.7 mPa·s, respectively, which was oil-in-water microemulsion without serious irritation or allergy for skin. The Js, Qn, and Qretention of MEs-Ap (0.81 ± 0.19 μg/cm2/h, 24.73 ± 4.24 μg/cm2, 2.08 ± 0.18 μg/cm2) were apparently higher than Differin® (0.022 ± 0.009 μg/cm2/h, 0.536 ± 0.103 μg/cm2, and 0.523 ± 0.130 μg/cm2) respectively. The local bioavailability study showed that the AUC0 → 36h of the MEs-Ap in the dermal (19.6 ± 1.22 μg/cm2) was significantly improved comparing to Differin® (13.9 ± 1.73 μg/cm2) (p < 0.01). The pharmacodynamics study showed that the therapeutic effect of MEs-Ap was better than that of Differin® in the acne model of rabbit auricle. These results suggested that the MEs-Ap could be considered as a having higher epidermal penetrability, dermal retention, local bioavailability, efficacy, and safety topical preparations for acne.

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Funding

This research was financially supported by Heilongjiang Postdoctoral Fund (NO. LBH-Z18144) and Excellent Young Talents Funding from College of Pharmacy, Harbin Medical University (NO. 2019-YQ-06).

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Authors and Affiliations

  1. Department of Pharmacy, the Second Affiliated Hospital, Harbin Medical University (Key Laboratory of medications research, college of Heilongjiang Province), 148 Baojian Road, Harbin, 150086, People’s Republic of China

    Bing Shao & Hongyu Ji

  2. Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, People’s Republic of China

    Lixin Sun & Hongyu Ji

  3. Department of Pharmacy, the Fourth Affiliated Hospital, Harbin Medical University, Harbin, 150086, People’s Republic of China

    Na Xu

  4. Department of Pharmacy, the First Affiliated Hospital, Harbin Medical University, Harbin, 150086, People’s Republic of China

    Hongwei Gu

  5. Department of Food and Environment Engineering, Heilongjiang East University, 1 Hanan Road, Harbin, 150086, People’s Republic of China

    Linhua Wu

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  1. Bing Shao
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Correspondence to Hongyu Ji or Linhua Wu.

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Shao, B., Sun, L., Xu, N. et al. Development and Evaluation of Topical Delivery of Microemulsions Containing Adapalene (MEs-Ap) for Acne. AAPS PharmSciTech 22, 125 (2021). https://doi.org/10.1208/s12249-021-01989-w

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  • DOI: https://doi.org/10.1208/s12249-021-01989-w

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