2012|13 Annual Report Fraunhofer IGB

74 1 μm SKIN HEAL – A PARTICLE-BASED FORMULATION FOR IMPROVED WOUND HEALING Dr. rer. nat. Carmen Gruber-Traub, Dr. rer. nat. Achim Weber The challenge of chronic wounds The effective and cost-efﬁcient treatment of chronic wounds is a great challenge in healthcare. Demographic changes have resulted in a constant increase in chronic wounds – above all, diabetic ulcers. Previously, the amputation of extremities and the associated loss in quality of life have often been unavoid- able. The development and evaluation of new forms of treat- ment for chronic skin disorders are therefore extremely impor- tant in regard to reducing costs and improving care. For the individual treatment of these chronic wounds we are devel- oping particle-based formulations within the Fraunhofer “Be- yond Tomorrow” project “SKIN HEAL”. The particles loaded with active agents can be integrated into commercial wound dressings or directly applied during treatment as pharmaceuti- cal formulations. Chitosan particles loaded with active agents by spray drying Various particle technologies were used at the Fraunhofer IGB to formulate micro- and nanoparticles loaded with active agents. We use small molecules or proteins as active phar- maceutical ingredients (APIs). Chitosan, as well as its deriva- tive chitosan hydrochloride, was chosen as the base material for the particles. Chitosan is a biobased, biocompatible poly- mer obtained from crustacean shells, which has antimicrobial properties. We have been able to successfully develop spray- drying procedures for the formulation of active agents that are implemented in wound healing, such as e.g., dexpanthe- nol or TGF-β (transforming growth factor). The Fraunhofer IGB has the Büchi Mini Spray Dryer B-290 and the Nano Spray Dryer B-90 available for this. The process parameters for spray drying using the Mini Spray Dryer were veriﬁed by design of experiments (DoE). This assures simple upscaling of the pro- cess parameters for the transmission of the spray drying pro- cess to the large-scale production process. Optimized particle size for optimal integration into the wound dressing Dexpanthenol and TGF-β-loaded chitosan and chitosan hy- drochloride particles can be produced using both the Mini and Nano Spray Dryer (Figs. 1 and 2). Design of experiments is, among other things, suitable for the optimization of the process parameters with regard to particle size. This process helped us to create a model that enables the targeted set- ting of the particle size (d50) during particle production in the Mini Spray Dryer. This allowed us to produce chitosan particles with deﬁned particle sizes of 2 μm, 5 μm and 10 μm. The par- ticles were integrated into ﬁbers of the CE certiﬁed silica ﬁber wound dressing (Fig. 4) at the Fraunhofer ISC. Chitosan parti- cles with a diameter smaller than 5 μm were most suitable for this. Crosslinking for controlled active agent release For the controlled release of the active agents, the chitosan and chitosan hydrochloride particles were crosslinked using ionic gelation with tripolyphosphate (TPP), and subsequent spray drying. The concentration of tripolyphosphate was var- ied and proportions of 0, 4, 7, 10 and 12 percent crosslinker 1 2 1 μm PHARMACY

2012|13 Annual Report Fraunhofer IGB

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