(T1430-01-03) Development of Film-Forming Gel Containing Ketoprofen with Improved Skin Permeability and Bioavailability

Purpose: This study aimed to develop a novel film-forming gel (FFG) using PVA as a film forming polymer with faster film formation time, a more flexible film, improved skin permeability, and bioavailability of poorly water-soluble ketoprofen.

Methods: The new ketoprofen-loaded FFG consists of ketoprofen, dextrin, glycerin, sodium bicarbonate, permeation enhancer, water, and ethanol (2.5/10/3/2.5/2.5/2.5/65.5/14, weight ratio) and manufactured with a mechanical stirrer. The film formation time was considered to be the time measured when the gel (0.2 g) was dried entirely at 38°C on an acrylic panel (3 cm x 4 cm). The elastic modulus, tensile strength, and elongation at break of the formed film (2 cm x 6 cm) were measured using a texture analyzer. In vitro skin permeability studies were also performed using a Franz diffusion cell maintained in phosphate buffer (pH = 7.4) and temperature maintained at 37°C. In permeability studies, formulations containing various permeation enhancers were evaluated compared to formulations without permeation enhancers. The formulation with the highest skin permeability was then studied in vivo in 8-week-old SD rats and compared to a ketoprofen gel containing no permeation enhancer. Their physicochemical properties were evaluated using DSC, SEM, FTIR, and PXRD.

Results: In this FFG, the gel quickly turns into a film within minutes, forming a flexible, transparent film over the skin. Additionally, poorly water-soluble ketoprofen was dissolved entirely in FFG by adjusting the pH with sodium bicarbonate. FFG formulations containing L-menthol and isopropyl myristate as permeation enhancers showed significantly improved permeability than formulations without enhancers. Subsequently, in the in vivo bioavailability evaluation, FFG containing a permeation enhancer showed higher bioavailability than FFG formulations that did not contain a permeation enhancer. Additionally, the physicochemical analysis showed that ketoprofen-loaded FFG converted the crystalline drug to an amorphous state.

Conclusion: Therefore, this FFG is a system with new potential for formulations used on skin with fast drying time and high film flexibility. It also improves skin permeability and the bioavailability of ketoprofen.

References: An Seop Han, Jaemin Kim, Jin Woo Park, Sung Giu Jin, Novel acyclovir-loaded film-forming gel with enhanced mechanical properties and skin permeability, Journal of Drug Delivery Science and Technology, Volume 70, 2022,103213, ISSN 1773-2247


Figure 1. Effect of plasticizer on tensile strength (A), break elongation (B), Young’s modulus (C), Effect of Ethanol ratio on Film formation time (D)


Figure 2. Skin permeation profiles of ketoprofen-loaded FFG


Figure 3. Ketoprofen plasma concentration-time profiles of ketoprofen-loaded FFG