Contents lists available at ScienceDirect Journal of Drug Delivery Science and Technology journal homepage: www.elsevier.com/locate/jddst Preparation and evaluation of QbD based fusidic acid loaded in situ gel formulations for burn wound treatment Neşe Buket Aksu a , Vildan Yozgatlı b , Mehmet Evren Okur c , Şule Ayla d , Ayşegül Yoltaş e , Neslihan Üstündağ Okur f,* a Altınbas University, School of Pharmacy, Department of Pharmaceutical Technology, Bakırköy, Istanbul, Turkey b Ege University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Bornova, Izmir, Turkey c University of Health Sciences, Faculty of Pharmacy, Department of Pharmacology, Üsküdar, Istanbul, Turkey d Istanbul Medipol University, School of Medicine, Department of Histology and Embryology, Beykoz, Istanbul, Turkey e Ege University, Faculty of Science, Department of Biology, Fundamental and Industrial Microbiology Division, Bornova, Izmir, Turkey f University of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Technology, Üsküdar, Istanbul, Turkey ARTICLE INFO Keywords: Fusidic acid Thermo-sensitive in situ gel QBD Burn treatment Topical Rat Microbiological study ABSTRACT The purpose of this research was to prepare and evaluate the potential use of in situ gel formulations for dermal delivery of fusidic acid for burn wound treatment. Temperature sensitive in situ gels were successfully developed by the cold technique using poloxamer 188, poloxamer 407, poloxamer 338. Finally, the concentration of fusidic acid in formulations was 2% (w/w). The developed formulations were optimized using quality by design (QbD) approach. The prepared formulations were evaluated for clarity, sol-gel transition temperature, gelling capacity, pH, viscosity and drug content. The gelation temperatures of all the fusidic acid loaded formulations were within the range of 30–34 °C. Furthermore, sterility, antibacterial activity, stability, in vitro fusidic acid release, ex vivo permeation, and penetration study of these formulations were also examined. The wound healing feature was appraised by determining the wound contraction and by a histopathological survey. Based on the observed antimicrobial and wound healing effects, the formulations containing fusidic acid could be employed as an alternative to commercial cream. This novel formulation can be employed for making burn wound healing process more efficient. 1. Introduction A wound can be defined as a defect in the skin, arising from thermal or physical damage or as a result of the existence of a medical or physiological situation. Other acute wounds comprise burns and che- mical damages, which come from various sources such as chemicals, electricity, radiation, and thermal. The temperature of the source and the exposure time efficacy the degree of a thermal burn [1,2]. Strong burn damages are the most traumatic damages affecting almost all or- gans and leading to significant morbidity [3,4]. In accordance with the World Health Organization, 180,000 deaths per year are concerned with burn damages [5]. The skin covers the whole body and serves as a line of defence against the external invasion of microorganisms and other peripheral stresses such as heat, entry of chemicals and toxins, as well as dehy- dration [6]. The stratum corneum is only between 20 and 25 μm thick but nevertheless ensures a very effective barrier towards penetration and the impermeability is a considerable problem in the delivery of medicines both to and through the skin [7]. Dermal drug delivery has the advantage that high concentrations of drugs can be localized at the site of action, reducing the systemic drug levels and therefore also de- creasing the systemic side effects [8]. The stiffness of gels is caused by gelling agents, which belong mainly to polymers. These polymers build up a three-dimensional network. Lately, an excellent overview not only of polymeric gels but also of other innovative gels was presented [7]. The gels can prove to be a beneficial carrier for the localized drug action on the skin. A gel is defined as a semisolid formulation, which exhibits an external solvent phase, and is immobilized within the spaces available of a three-di- mensional network structure. Compared to creams and ointments, gels, because of their high water content, permit a greater dissolution of drugs and facilitate migration of the drug through the carrier. More- over, gels can hydrate the skin by retaining a significant amount of transepidermal water and facilitate drug transport [6]. In situ activated https://doi.org/10.1016/j.jddst.2019.04.015 Received 13 December 2018; Received in revised form 21 March 2019; Accepted 13 April 2019 * Corresponding author. University of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Technology, Uskudar, 34668, Istanbul, Turkey. E-mail address: neslihanustundag@yahoo.com (N. Üstündağ Okur). Journal of Drug Delivery Science and Technology 52 (2019) 110–121 Available online 17 April 2019 1773-2247/ © 2019 Elsevier B.V. All rights reserved. T