Optimization of Film-Dressings Containing Herbal Extracts for Wound Care-A Quality by Design Approach.

Despite the potential of film dressings for wound healing, many formulations lack an optimized design in order to ensure that the ingredients were carefully chosen to increase the product's efficacy and stability, while also ensuring the patient's comfort during the treatment. Moreover, commercially available film dressings do not contain herbal extracts or other active substances with wound healing properties, highlighting a gap in the market and the need for further research in this direction. The aim of this work was the development and optimization of a bio-inspired formulation of a complex herbal extract-loaded film-dressing to be used in wound care, using the quality by design approach. After setting the quality target product profile with the critical quality attributes and undergoing the risk assessment, the design of experiments was implemented. All the selected ingredients were biodegradable, aligning with the current need for a natural approach, based on their biocompatibility and reduced environmental impact. A D-optimal experimental plan was used, in which the types and concentrations of film-forming agents and plasticizers were varied: xanthan gum, acacia gum, sodium carboxymethylcellulose and glycerol, 1,3-propanediol, and xylitol, respectively. All formulations contained polyvinyl alcohol and a previously studied complex herbal extract. The films were characterized in terms of uniformity of mass, film thickness, swelling degree, folding endurance, adhesive, and mechanical properties. The optimized formulation was achieved by maximizing the swelling degree, adhesive properties, hardness, deformation at target, and elongation at break. The optimized film was characterized, and the in vitro total polyphenolic content release from the film was evaluated. Following the understanding of the influences of the formulation factors on the film characteristics, the composition of the optimized film-dressing was determined as follows: 5% polyvinyl alcohol, 0.25% xanthan gum, 10% glycerol, and 20% complex herbal extract. The optimized film exhibited high swelling degree (627.28%), high adhesive properties (adhesive force of 28.00 g and adhesiveness of 0.20 mJ), high elasticity (deformation at target of 29.80%, and elongation at break of 106.90%), as well as good mechanical properties (hardness of 2616.00 g), which are suitable characteristics for use on wounds. Moreover, the optimized film-dressing exhibited a sustained release, with a maximum release of polyphenols of 88.00% after 8 h.