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

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.

A Randomized, Double-Blind, Placebo-Controlled, Multicentric Study to Evaluate the Efficacy and the Tolerability of a Class II Medical Device in the Treatment of Mild and Moderate Acne

“…A major issue related to the use of azelaic acid in topical formulations is its irritant potential on the skin; this side effect, which is generally temporary, may manifest itself as itching or tingling [ 31 ]. This poses the need for compositions that can deliver azelaic acid, while substantially reducing or eliminating the side effects [ 32 , 33 ]. One example is that represented by polyglycerol-azelaic acid, a polyester obtained by reacting or condensing azelaic acid with polyglycerols that shows better tolerability compared with azelaic acid [ 34 ].…”

Preparation, Optimization, and Investigation of Naringenin-Loaded Microemulsion for Topical Application

“…In a test tube, NAR was introduced to the oil phase, followed by the s/c combination in two phases, and finally water was added dropwise. Vortex and sonicator were used at all steps to mix the components and obtain a transparent NAR ME [ 14 ] .…”

Foray into Concepts of Design and Evaluation of Microemulsions as a Modern Approach for Topical Applications in Acne Pathology

“…A full factorial design was used to achieve information about the internal structure, and it was concluded that the composition will influence the ME properties, as can be observed in Table 4 . Hence, by choosing a high amount of S/CoS mix, a large area of ME can be promoted, which can be easily depicted on the pseudoternary phase diagram [ 309 ].…”