Novel In Vitro Investigational Methods for Modeling Skin Permeation: Skin PAMPA, Raman Mapping

Abstract

The human skin is marked as a standard by the regulatory agencies in the permeation study of dermal formulations. Artificial membranes can substitute human skin to some extent. Academicians and pharmaceutical corporations are focusing their efforts on developing standardized protocols and safe, reliable options to substitute human skin for carrying out permeability studies. Our research aim was to study the applicability of new techniques in the case of different types of dermal formulations. The skin parallel artificial membrane permeability assay (PAMPA) method and Raman mapping were compared to the gold-standard Franz cell method. A hydrogel and two types of creams were investigated as the most generally used dermal preparations. The values of the diffused drug were closer to each other in PAMPA and Franz cell measurement. The diffused amount of drug showed the same order for the different formulations. These results correlate well with the results of Raman mapping. Our conclusions suggest that all early screening examinations can be performed with model tools such as skin PAMPA supplemented with methods like Raman mapping as a semi-quantitative method.

Comparison of Synthetic Membranes to Heat-Separated Human Epidermis in Skin Permeation Studies In Vitro

“…It was designed to predict transdermal permeation in a quick, reliable, and cost-effective way [22]. The Skin PAMPA can be used for semisolids [24] and patch formulations [30] as well; it was found to correlate with ex vivo permeation studies [31]. The shortcoming of the Skin PAMPA membrane is that it does not represent the biological complexity of skin, and it does not contain, e.g., proteins, corneocytes, and special lipid subclasses of human skin [32,33].…”

“…The examination lasted 12 h (sampling times: 0.5; 1; 2; 4; 6; 12 h). The amount of permeated drug was determined at a wavelength of 275 nm with Thermo Scientific Evolution 201 spectrometer using Thermo Insight v1.4.40 software package (Thermo Fisher Science, Waltham, MA, USA) [24]. Measurements were also performed with each drug-free formulation.…”

“…After heating (60 • C), purified water was emulsified in the oil phase under stirring. Finally, DFNα was added and homogenized [24].…”

The Implications of Regulatory Framework for Topical Semisolid Drug Products: From Critical Quality and Performance Attributes towards Establishing Bioequivalence

“…Although these artificial skin surrogates offer numerous advantages (e.g., defined thickness, composition, ease in handling and storage, and reproducibility in the permeation data), the correlation with the human data is often poor, due to inability to completely recreate the heterogeneous nature of the skin, including cell metabolism and skin appendages. Consequently, skin surrogates are currently recommended for the early screening of different formulations, while human skin should be used for the in vitro permeation testing of finished drug products [ 55 , 56 ].…”

Investigation of passive and active permeation enhancement methods on skin permeation

“…The characteristic peaks of the pure LID-HCl could not be fitted to the spectra of treated skin samples because the concentration of LID-HCl was low in the formulations. Therefore, the spectrum of REF formulation, which contains 5 wt% LID-HCl but without the glycols, was used to obtain the correlation maps, which indicates the presence of LID-HCl in the skin as well [93,94]. A correlation map for the untreated sample was used as a control map.…”