Simultaneous Physico-Mechanical and In Vivo Assessment towards Factual Skin Performance Profile of Topical Polymeric Film-Forming Systems

Abstract

Topical film-forming systems (FFS) change drastically after solvent displacement, therefore indicating their skin metamorphosis/transformation as a property of special regulatory and research interest. This paper deals with the lack of suitable characterization techniques, suggesting a set of methods able to provide a comprehensive notion of FFS skin performance. After screening the physico-chemical, mechanical and sensory properties of FFS and resulting films, an elaborate three-phase in vivo study was performed, covering skin irritation, friction and substantivity. Upon removal of 24-hour occlusion, no significant change in erythema index was observed, while the film-former type (cellulose ether, acrylate and/or vinyl polymer) affected transepidermal water loss (TEWL); hydrophobic methacrylate copolymer-based samples decreased TEWL by 40–50%, suggesting a semi-occlusive effect. Although both the tribological parameters related to the friction coefficient and the friction curve’s plateau provided valuable data, their analysis indicated the importance of the moment the plateau is reached as the onset of the secondary formulation, while the tertiary state is still best described by the completion of the film’s drying time. The final part of the in vivo study proved the high in-use substantivity of all samples but confirmed the optimal 4:1 ratio of hydrophobic cationic and hydrophilic polymers, as indicated during early physico-mechanical screening.

Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study

“…The results of the tribology study published in our previous paper [ 15 ] correlate well with the abovementioned AFM-mediated observations. Smoother films require less force from the Frictiometer probe, resulting in lower friction values and vice-versa.…”

“…Lower viscosity also implies faster lateral spreading of a product on the skin. Furthermore, the obtained viscosity values correlated well with the results obtained in our previous study [ 15 ], which encompassed an in vivo substantivity assay of ‘placebo’, i.e., drug-unloaded FFSs, wherein the level of skin substantivity was in the following order: S3 > S2 > S1. Therefore, early-stage rheology of FFS may provide a notion of bioadhesive and skin-retention properties of a polymeric formulation.…”

“…Formulation S2A was found to have the highest pH value of 7.7. pH values spanning the basic half of the pH scale could potentially provide more favorable dermal absorption [ 20 ]. The obtained findings imply that BDP-loaded FFSs would not produce either skin irritation or any other patient discomfort, as previously confirmed in vivo for corresponding samples without this model active substance [ 15 ].…”

“…Considering the fact that the chosen FFS formulations stemmed from a previous study [ 15 ] and therefore differ in film-forming polymer type and/or concentration, the heterogeneous results presented within Table 3 were somewhat expected. The important thing to note is that the incorporation of BDP in the investigated FFS failed to induce a significant change of the monitored physicomechanical properties, meaning that BDP precipitation was unlikely to occur during product metamorphosis and subsequent film formation.…”

“…After assessing fundamental physicochemical, mechanical and tribological properties further reinforced with biocompatible and biosubstantive features of a series of FFSs [ 15 ], the refined number of samples was selected to enter the next stage of the study, aiming to assess precise film morphology and potential molecular interactions within such dynamic system. The dipropionate ester of betamethasone, herein chosen as the model active substance, is a potent corticosteroid frequently used in treatments of different types of dermatitis and chronic plaque psoriasis localized on elbows, knees, scalp and feet [ 16 , 17 , 18 ].…”