Evaluation of Avenanthramide-A as a skin penetration enhancer: In vitro and in vivo testing on permeation of Magnesium ascorbyl phosphate and Diclofenac sodium from topical gels

Topical and transdermal drug delivery are favored to deliver active pharmaceutical ingredients directly to the skin as an alternative to oral administration for systemic effects. In either case, the active molecules must cross the stratum corneum and epidermis to reach the site of action. The stratum corneum serves as a primary barrier limiting compounds from fully penetrating the skin. Therefore, it is necessary to add penetration enhancers to topical formulations to enhance drug delivery through the skin. Often, penetration enhancers are also irritant to the skin. Earlier research in our pharmaceutical laboratory showed that an addition of colloidal oatmeal, produced through fine grinding of oat kernels (Avena sativa), significantly improved the overall permeability of fingolimod hydrochloride from a topical gel formulation. Although, there was a need to further investigate which component of colloidal oatmeal potentially leads to permeation enhancement with minimal irritant effects. Colloidal oatmeal is all-natural powder containing a mixture of components and majorly antioxidants like Avenanthramides (AVAs) with a long history of promising effects in dermatology. AVAs are low molecular weight phenolic alkaloids which had never been examined before for penetration enhancement. Avenanthramide-A (AVA-A) extract was readily available from a Canadian biotechnology company to put to the test. The objective of this study was to evaluate whether AVA-A, one of the major AVA found in oat kernels, alongside AVA-B and AVA-C which are also prevalent in oat grains, may possess permeation-enhancing properties. In our study, Klucel 2% hydroxypropyl cellulose topical gels were prepared in laboratory with a high-speed homogenization technique using conventional excipients and active ingredients; magnesium ascorbyl phosphate (MAP) and diclofenac sodium (DCF). MAP or DCF 2% gels were found to be homogeneous, stable and maintained a consistent appearance with time. AVA-A at varying concentrations of 1%, 5% and 10% was added in prepared gels to assess its capability in MAP or DCF permeation enhancement through the skin compared to a control gel containing 0% AVA-A. In vitro studies were carried out with Franz diffusion cells. In vitro release testing studies used a cellulose membrane and in vitro permeation testing studies used an excised dorsal porcine ear skin. In vitro permeation testing studies showed MAP or DCF gels containing 5% or 10% AVA-A significantly (p< 0.01) increased percutaneous permeability compared to control gels. Topical gels containing 10% AVA-A showed the highest in vitro permeation. In vitro studies presented a starting point that AVA-A may be a potential permeation enhancing agent. To further confirm in vitro findings, gels were evaluated in vivo in New Zealand albino rabbit model using dermal microdialysis technique to measure cutaneous pharmacokinetics of the actives. In vivo studies showed MAP gel containing 5% AVA-A increased dermal maximum concentration and area under the curve by 2.11 ± 1.81-fold and 4.02 ± 2.77-fold respectively. On the other hand, DCF gel with 5% AVA-A showed an increase by 2.56 ± 2.39-fold and 4.13 ± 3.48-fold respectively. MAP and DCF gels containing 10% AVA-A displayed an increase in dermal maximum concentration and area under the curve by 2.02 ± 1.60-fold and 1.83 ± 1.54-fold respectively, and 2.09 ± 2.00-fold and 3.71 ± 2.77-fold respectively. Topical gels containing 5% AVA-A showed the highest in vivo permeation. Addition of 10% AVA-A in vivo decreased the permeation of MAP or DCF, probably due to the rabbit skin developing resistance to the permeation of actives at higher AVA-A concentration. Besides, our study also estimated DCF disposition function within the dermis termed ‘dermal unit impulse response’ via retrodialysis/microdialysis (dermal infusion) approach. Comprehensively, both in vitro and in vivo studies showed MAP or DCF 2% gels containing 5.00% or 10.00% AVA-A has significant (p< 0.05) permeability characteristics for delivery of actives to the skin. In conclusion, AVA-A may be a promising skin penetration enhancer of natural origin.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.