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Biopharmaceutical Assessment and Irritation Potential of Microemulsions and Conventional Systems Containing Oil from Syagrus cearensis for Topical Delivery of Amphotericin B Using Alternative Methods

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Abstract

The aim of this study was to compare the biopharmaceutical characteristics and irritation potentials of microemulsions (MEs) and conventional systems (CSs) containing oil from Syagrus cearensis for topical delivery of Amphotericin B (AmB). Pseudo-ternary phase diagrams were constructed using a water titration method to develop the MEs, and the CSs were prepared according to the classical technique of phase inversion. In the skin permeation and retention study, dermatomed pig skin without stratum corneum was used as an alternative disturbed skin model. The irritation potential was evaluated using three different methods, chorioallantoic membrane assays (HET-CAM and CAM-TBS), and bovine corneal opacity and permeability (BCOP) test. The optimized formulation (ME1) consisting of 0.1% (w/w) Amphotericin B, 9.1% (w/w) catolé oil, 81% (w/w) Smix (1:1, Tween 20 and Kolliphor EL) possessed droplet size of 31.02 ± 0.9 nm, zeta potential of −23.4 mV, and viscosity 0.63 ± 0.1 Pa.s. ME1 exhibited greater retention of AmB in to skin layers (84.79 ± 2.08 μg cm−2) than all the others formulations. In general, MEs showed higher drug release and retention than CSs and all of the formulations showed greater retentivity than permeability. Only MEs developed using Labrasol/Plurol Oleique (L/PO) as the surfactant and co-surfactant exhibited a moderate irritation potential; all other MEs and CSs were classified as non-irritants or slight irritants. The results indicate that formulations containing oil from S. cearensis are promising alternatives for the delivery of AmB targeting the treatment of cutaneous leishmaniasis.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, Brazil

    Giovana D. Sousa, Juliana Kishishita, Leila B. Leal & Davi P. Santana

  2. Department of Nuclear Energy, Federal University of Pernambuco, Recife, Brazil

    Kátia A. S. Aquino

  3. Oswaldo Cruz Foundation - Fiocruz, Rio de Janeiro, Brazil

    Octávio A. F. Presgrave

Authors
  1. Giovana D. Sousa
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  2. Juliana Kishishita
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Correspondence to Giovana D. Sousa.

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Sousa, G.D., Kishishita, J., Aquino, K.A.S. et al. Biopharmaceutical Assessment and Irritation Potential of Microemulsions and Conventional Systems Containing Oil from Syagrus cearensis for Topical Delivery of Amphotericin B Using Alternative Methods. AAPS PharmSciTech 18, 1833–1842 (2017). https://doi.org/10.1208/s12249-016-0663-3

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