Development and Evaluation of Azelaic Acid-Loaded Microemulsion for Transfollicular Drug Delivery Through Guinea Pig Skin: A Mechanistic Study.

Anayatollah Salimi,Behzad Sharif Makhmal Zadeh,Abbas Rahdar,Salar Godazgari

doi:10.34172/apb.2020.028

Anayatollah Salimi, Behzad Sharif Makhmal Zadeh + Show 2 more

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https://doi.org/10.34172/apb.2020.028

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Abstract

Purpose: Azelaic acid is a natural keratolytic, comedolytic, and antibacterial drug that is used to treat acne. The topical application of azelaic acid is associated with problems such as irritation and low permeability. For dissolving, the problem is that microemulsion (ME) is used as a drug carrier. The aim of this study was to increase the azelaic acid affinity in the follicular pathway through ME. Methods: Azelaic acid-loaded MEs were prepared by the water titration method. The properties of the MEs included formulation stability, particle size, drug release profile, thermal behavior of MEs, the diffusion coefficient of the MEs and skin permeability in the non-hairy ear skin and hairy abdominal skin of guinea pig were studied in situ. Results: The MEs demonstrated a mean droplet size between 5 to 150 nm. In the higher ratios of surfactant/co-surfactant, a more extensive ME zone was found. All MEs increased the azelaic acid flux through both hairy and non-hairy skin compared with an aqueous solution of azelaic acid as a control. This effect of the ME was mainly dependent on the droplet diffusion coefficient and hydrodynamic radius. MEs with a higher diffusion coefficient demonstrated higher azelaic acid flux through hairy and non-hairy skin. Drug flux through both skins was affected by the surfactant/co-surfactant ratio in that the higher ratio increased the azelaic acid affinity into the follicular pathway. Conclusion: Finally, the ME with the highest droplet diffusion coefficient and the lowest surfactant/co-surfactant ratio was the best ME for azelaic acid delivery into the follicular pathway.

Highlights

Acne vulgaris is a multifunctional disease of the pilosebaceous unit that may present at any age and it is associated with various clinical presentations such as comedones, papules, pustules and nodules
Phase behavior studies For the determination of the ME zone based on the different surfactant ratio (S/C) ratios two phase, diagrams were drawn (Figure 1)
Azelaic acid is an anti-acne agent with poor permeation through the skin that diminishes its therapeutic effectiveness and increases the skin irritant potency

Summary

Introduction

Acne vulgaris is a multifunctional disease of the pilosebaceous unit that may present at any age and it is associated with various clinical presentations such as comedones, papules, pustules and nodules. Topical treatment is the main choice for mild and moderate acne.[2] Most of the conventional topical formulation usually demonstrates a high incidence of side effects that reduce patient compliance and the efficacy of the therapy. Azelaic acid is an effective compound for the topical treatment of mild to moderate acne vulgaris.[3] The therapeutic Formula 20% azelaic acid cream formulation has been proven in the treatment of acne (comedone, pustular, nodular) but its therapeutic effects may not be seen for up to 4 weeks after use. The patient should continue therapy for more than 6 months.[4] After the topical application of 1 g of 20% azelaic acid cream, a percutaneous absorption of about 3% and plasma concentration of 0.038 μg/mL were estimated.[5] low dermal absorption diminishes its therapeutic effectiveness. The azelaic acid concentration in the hair follicles is affected by the nanocarriers

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