Pilot scale-up and shelf stability of hydrogel wound dressings obtained by gamma radiation Dulce Marı ´a Soler a,n , Yanet Rodrı ´guez a , Hector Correa a , Ailed Moreno b , Lila Carrizales b a National Center for Animal and Plant Health (CENSA), Development and Industrial Biotechnology Group, San Jose´ de las Lajas, Mayabeque, Cuba b Venezolan Institute of Scientific Research (IVIC), Nuclear Technology Unit, Altos de Pipe, Caracas 1020A, Venezuela article info Article history: Received 1 July 2011 Accepted 16 February 2012 Available online 24 February 2012 Keywords: Hydrogel Poly(vinyl pyrrolidone) Wound dressing Scale-up Stability abstract This study is aimed of producing pilot batches of hydrogel wound dressings by gamma radiation and evaluating their shelf stability. Six batches of 3L capacity were prepared based on poly(vinyl pyrrolidone), agar and polyethylene glycol and they were dispensed in polyester trays, covered with polyester films and sealed in two types of materials: polyethylene bags and vacuum polyethylene bags. Dressings were formed in a single step process for the hydrogel formation and sterilization at 25–30 kGy gamma radiation dose in a JS-9500 Gamma Irradiator (Nordion, Canada). The six batches were initially physicochemical characterized in terms of dimensions and appearance, gel fraction, morphology analysis, hydrogel strength, moisture retention capability and swelling capacity. They were kept under two storage conditions: room temperature (T: 30 72 1C/RH: 70 7 5%) and refrigerated temperature (T:5 73 1C) during 24 months and sterility test was performed. The appearance of membranes was transparent, clear, uncut and flexible; the gel fraction of batches was higher than 75% and the hydrogel surface showed a porous structure. There was a slow decrease of the compression rate 20% until 7 h and about 70% at 24 h. Moisture retention capability in 5 h was similar for all the batches, about 40% and 60% at 37 1C and at room temperature respectively. The swelling of hydrogels in acidic media was strong and in alkaline media the weight variation remains almost stable until 24 h and then there is a loss of weight. The six batches remained sterile during the stability study in the conditions tested. The pilot batches were consistent from batch to batch and remained stable during 24 months. & 2012 Elsevier Ltd. All rights reserved. 1. Introduction Hydrogels are bi or multicomponent systems consisting in a permanent three-dimensional network of linked polymer chains, and molecules of a solvent filling the pores of this network. They are obtained by polymerization with crosslinking agents, by chemical crosslinking of polymers or by radiation-induced cross- linking of polymers. The radiation processing has several advan- tages such as the simultaneous crosslinking and sterilization in one step and the easy control of physical properties of hydrogels by combining dose with polymer composition; it allows to fabricate a pure and human-friendly product non-contaminated with ballast materials or the residuals of toxic initiators (Lugao and Malmonge, 2001; Rosiak et al., 1995). Hydrogels based on polyvinylpyrrolidone (PVP), agar and poly(ethylene glycol) (PEG) firstly developed as wound burn dressings by Dr. Rosiak from Poland (Rosiak et al., 1989) have had a successfully wide application for medical treatment of other types of wounds and illnesses since their market introduction in 1992. These biomaterials should fulfill some requirements that are mentioned by Rosiak et al. (1995): absorb effectively the body fluids and prevent their loss, act as an efficient barrier against bacteria, adhere well to the wound but stronger to healthy skin, exhibit high elasticity but also some mechanical strength, show good transparency, enable the oxygen to penetrate through the volume of dressing to the wound surface, enable to control drug dosage and offer good handling (i.e. easy placement and replace- ment) without pain. In addition they should be sterile, easy to store, relatively cheap and generally accelerate healing. The International Atomic Energy Agency (IAEA) has supported the technical cooperation related to the development of this kind of product in the laboratories of developing countries like Cuba. To develop the total production process of our product, it is necessary to follow the product life cycle that goes through multiple phases, involves many professional disciplines, and requires many skills, tools and processes (Westk¨ amper, 2000). After the laboratory tests, it is important to demonstrate the scalability of the process and the product stability. Scale-up is generally defined as the process of increasing the batch size. In moving from R&D to pro- duction scale, it is sometimes essential to have an intermediate Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/radphyschem Radiation Physics and Chemistry 0969-806X/$ - see front matter & 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.radphyschem.2012.02.024 n Corresponding author. Tel.: þ53 047863653. E-mail address: dmsoler@censa.edu.cu (D.M. Soler). Radiation Physics and Chemistry 81 (2012) 1249–1253