Film-Forming Gels for Topical Drug Delivery: A Systematic Review of the Effects of Formulation on Film Performance, Drug Release, and Skin Permeation

Ferdy Firmansyah,1,2 Arif Budiman,3 Muchtaridi Muchtaridi,4 Lutfi Chabib,5 Fauzia Ningrum Syaputri,6 Fauzan Afandi,3 Khaled M Elamin,7 Ahmed Fouad Abdelwahab Mohammed,8,9 Nasrul Wathoni3 1Doctoral Program of Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia; 2Department of Pharmacy, Sekolah Tinggi Ilmu Farmasi Riau, Pekanbaru, Riau, Indonesia; 3Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia; 4Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia; 5Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Indonesia, Yogyakarta, Indonesia; 6Department of Pharmacy, Faculty of Pharmacy, Universitas Muhammadiyah Bandung, Bandung, West Java, Indonesia; 7Graduated School of Pharmaceutical Science, Kumamoto University, Kumamoto, Japan; 8Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt; 9Department of Pharmaceutics, Faculty of Pharmacy, Minia National University, Minia, EgyptCorrespondence: Nasrul Wathoni, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia, Tel +62-22-842-888-888, Email [email protected]: Film-forming gels (FFGs) are increasingly recognized as a medium for topical drug delivery. However, existing evidence correlating specific formulation characteristics with drug delivery efficacy remains fragmented across many studies and is only partially organized. This systematic review aimed to consolidate these findings into a single framework and examine how important formulation variables affect three main outcome domains: film characteristics, drug release behavior, and skin permeation. A systematic search of PubMed and Scopus was conducted until October 2025, adhering to the PRISMA criteria. Studies were included if they examined topical FFG formulations and reported at least one of the predetermined outcomes. A total of 27 studies fulfilled the inclusion criteria, with solvent evaporation identified as the predominant method for FFG preparation. Across this body of research, the selection and relative ratio of polymers and plasticizers have consistently emerged as critical determinants influencing drying time (< 15 min), mechanical strength, flexibility, and bioadhesive properties of the film on the skin. Most formulations released the drug slowly over approximately 8– 48 hours. In studies that measured permeation, FFGs usually exhibited a higher flux and/or better drug retention in the skin than regular topical formulations. The film’s ability to block the skin and the use of penetration enhancers in the matrix are thought to cause these effects. In summary, these results show that FFGs are a flexible and customizable formulation platform, where the film’s characteristics, release rate, and skin penetration are all strongly linked to the composition’s design. To obtain this technology with clearer therapeutic benefits, we need to employ Quality by Design principles more widely and have more consistent evaluation methodologies across studies.Keywords: film-forming gels, topical drug delivery, film properties, drug release, skin permeation