RESEARCH ARTICLE – Pharmaceutics, Drug Delivery and Pharmaceutical Technology Development and Characterization of a Hydrogel Containing Silver Sulfadiazine for Antimicrobial Topical Applications KARIN S. P. JODAR, 1 VICTOR M. BALC ˜ AO, 1,2,3 MARCO V. CHAUD, 1 MATTHIEU TUBINO, 3 VALQU ´ IRIA M. H. YOSHIDA, 1 JOS ´ E M. OLIVEIRA JR, 1 MARTA M. D. C. VILA 1,3 1 LaBNUS – Biomaterials and Nanotechnology Laboratory, i(bs) 2 – Intelligent Biosensing and Biomolecule Stabilization Research Group, University of Sorocaba, Sorocaba, S˜ ao Paulo, Brazil 2 CEB – Centre of Biological Engineering, University of Minho, Braga, Portugal 3 Institute of Chemistry, University of Campinas, Campinas, S˜ ao Paulo, Brazil Received 26 January 2015; revised 8 April 2015; accepted 13 April 2015 Published online 7 May 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jps.24475 ABSTRACT: Development and optimization of a hydrogel with impregnated silver sulfadiazine was pursued, for antimicrobial topical applications. The selected hydrogel exhibited a homogeneous appearance, with whitish colloration and devoid of any fractures or cracks. The content in impregnated silver sulfadiazine was within established limits (1%, w/w) with a standard deviation of up to 1.28%. The hydrogel presented a good characteristic in relation to release of the active antimicrobial principle, verified through swelling tests and antimicrobial activity. The swelling tests indicated a higher increase in weight during the first 6 h of contact with a moist environment, with a maximum value of 266.00 ± 0.81, and with maintenance of the original shape of the hydrogel. The impregnated silver sulfadiazine presented antimicrobial activity, as expected, indicating a prolonged release of the drug. The infrared spectra of the hydrogel with impregnated silver sulfadiazine indicated that the drug did not engage in any bonds with the polymeric matrix, which otherwise could have reduced its antimicrobial activity. The mechanical resistance tests produced good results, indicating that the hydrogels may be utilized in different locations of the human body with skin lesions. C  2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2241–2254, 2015 Keywords: hydrogels; PVA; silver sulfadiazine; antimicrobial topical applications; physical characterization; polymeric drug delivery systems; skin; transdermal drug delivery INTRODUCTION Among the various dosage forms developed as modified-release systems, hydrogels can be considered controlled-release sys- tems for drugs of topical application, depending on both the type of formulation and application in which they are used. 1 Hydrogels are three-dimensional (3D) networks of hydrophilic polymers that, in contact with water, swell and may release the drug by different mechanisms. 2 In this sense, hydrogels are of particular interest in the treatment of topical wounds because of their intrinsic low toxicity, potential for extended release of drugs, and the ability to keep the wound hydrated. 3–5 Review studies have pointed toward the use of various types of natu- ral and/or synthetic polymers for the preparation of hydrogels, such as poly(acrylic acid), poly(ethylene oxide), poly(ethylene glycol) (PEG), poly(vinyl pyrrolidone), polyvinyl alcohol (PVA), polyglycerol esters of fatty acids, carbomers, sodium alginate, chondroitin sulfate, pectin, dextran, carboxymethylcellulose, and other cellulose derivatives, chitosan, gelatin, and gums. 6–11 PVA is extensively used to produce hydrogels aiming at the treatment of topical ulcers. PVA is a nontoxic, biocompatible polymer that has excellent film-forming properties and ease of processability, as well as mechanical, thermal, and chemical resistances. 5,10,12,13 Dextrans are also widely used for biomed- Correspondence to: Marta M. D. C. Vila (Telephone: +55-15-2101-7181; Fax: +55-15-2101-7000; E-mail: marta.vila@prof.uniso.br) Journal of Pharmaceutical Sciences, Vol. 104, 2241–2254 (2015) C  2015 Wiley Periodicals, Inc. and the American Pharmacists Association ical applications because of their biocompatibility and ease of modification and biodegradation. 14 For the treatment of skin le- sions, among various substances, there is a consensus in the use of silver sulfadiazine at 1% (w/w) for the treatment of burns and skin infections. Silver sulfadiazine is effective against a wide microbiota of gram-negative bacteria such as Escherichia coli, Enterobacter, Klebsiella, and Pseudomonas aeruginosa, includ- ing also gram-positive bacteria such as Staphylococcus aureus and yeasts such as Candida albicans. 15 Silver sulfadiazine is in- dicated in the treatment and prevention of infections in burns, with classification of anti-infectant agent in the form of cream at 1% (w/w); short-term adjuvant treatment, for infections in both leg ulcers and pressure ulcers; prophylaxis of infection in areas of skin grafts prone to abrasion. 16 Silver sulfadiazine in the form of cream requires multiple daily applications, in- terfering with the healing process as the wound dressing ex- poses patients to infectious agents, in addition to the pain and trauma that it causes because the cream is not biodegradable and requires removal before reapplication. 17 Considering the growing importance of the pharmaceutical form hydrogel, the aim of the present research work was to develop and evaluate a hydrogel using PVA and/or dextran as raw materials, contain- ing incorporated silver sulfadiazine, for antimicrobial topical applications. The optimized hydrogel formulation integrating silver sulfadiazine was subsequently fully characterized physicochemically, encompassing determination of pore size and porosity via X-ray tomography, surface morphology via scanning electron microscopy (SEM), thermal analyses via thermogravimetric analysis (TGA), and differential scanning Jodar et al., JOURNAL OF PHARMACEUTICAL SCIENCES 104:2241–2254, 2015 2241