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In Vitro Skin Retention and Drug Permeation through Intact and Microneedle Pretreated Skin after Application of Propranolol Loaded Microemulsions

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Abstract

Purpose

Topical beta-blockers are efficacious for treating infantile hemangiomas, but no formulations have been specifically optimized for skin delivery. Our objective was to quantify skin concentrations and drug permeation of propranolol (a nonselective beta-blocker) after application of microemulsions to intact and microneedle pretreated skin.

Methods

Four propranolol-loaded microemulsions were characterized for droplet size, surface charge, conductivity, pH, drug solubility, and drug release. Skin concentrations and drug permeation through skin were quantified using LC-MS. Skin-to-receiver ratios were used to compare the microemulsion formulations to a drug-in-PBS solution.

Results

Propranolol solubility was significantly greater in microemulsions vs PBS. Cumulative drug release from the microemulsions over 24 h ranged from 13 to 26%. Skin concentrations and drug permeation through intact skin was significantly higher from PBS; however, the skin-to-receiver ratios were significantly higher for water-rich microemulsions compared to PBS or surfactant-rich microemulsions. Microneedle pretreatment significantly increased skin concentrations for all formulations. Skin-to-receiver ratios significantly increased after microneedle pretreatment for surfactant-rich microemulsions.

Conclusions

Microemulsion formulation can be altered to elicit different drug delivery profiles through MN-treated skin. This could be advantageous for maximizing local skin drug concentrations and improving dosing schedules for infantile hemangioma treatment.

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Abbreviations

ER:

Enhancement ratio

IH:

Infantile hemangioma

MN:

Microneedle

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by NIH grant R35GM124551.

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Authors and Affiliations

  1. Department of Pharmaceutical Science and Experimental Therapeutics, University of Iowa College of Pharmacy, 115 South Grand Avenue, PHAR S421, Iowa City, Iowa, 52242-1112, USA

    Megan N. Kelchen & Nicole K. Brogden

  2. Department of Dermatology, University of Iowa Carver College of Medicine, 200 Hawkins Dr, Iowa City, Iowa, 52241, USA

    Nicole K. Brogden

Authors
  1. Megan N. Kelchen
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  2. Nicole K. Brogden
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Correspondence to Nicole K. Brogden.

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Kelchen, M.N., Brogden, N.K. In Vitro Skin Retention and Drug Permeation through Intact and Microneedle Pretreated Skin after Application of Propranolol Loaded Microemulsions. Pharm Res 35, 228 (2018). https://doi.org/10.1007/s11095-018-2495-1

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