Physicochemical and wound tensile-strength studies in the development of a cream formulation for application during the acute and post-acute rehabilitation phases following limb amputation

Abstract

The full-scale war in Ukraine has led to a humanitarian crisis and has placed a significant burden on the healthcare system, particularly in the fields of traumatology, rehabilitation, and medical support for disabled people. From 2022 to 2024, more than 90,000 amputations were documented in Ukraine, most amputations are of the lower limbs, which created an increased demand for modern healthcare and rehabilitation products. Particularly important became ensuring proper stump care – a key component of the amputation recovery process, which is often underestimated. The aim of this study was the scientific substantiation, development, and testing of the composition of a semisolid medicinal formulation based on modern excipients and active pharmaceutical ingredients (glucosamine hydrochloride, miramistin, dexpanthenol, vitamin D) for stump care after amputation. To achieve this goal, a comprehensive study of the physico-chemical and structure-mechanical properties of the developed samples was carried out, as well as an evaluation of their pharmacological (reparative) effectiveness using scar tensile strength as a parameter in a linear incision wound model. It was established that the emulsifier content significantly affects the structure-mechanical and adhesive properties of creams intended for stump care. The best ratio of parameters was observed in the sample containing 5% emulsifier. The bioadhesion of creams decreases under the influence of electrolytes. The most pharmacologically effective were prototype formulations with glucosamine hydrochloride alone and in combination with miramistin, which outperformed the comparison drug (gel Pantestin-Darnitsa) in a model of a linear cut wound in rats. These formulations produced a statistically significant increase in scar tensile strength, while gel Pantestin-Darnitsa was at the trend level. It was shown that variations in the content of emulsifier, glycerin, and silicone components significantly influence the structural-mechanical, microstructural, and bioadhesive properties of the formulation. Samples with the optimal ratio of these components demonstrated high stability, uniform microstructure, and a sufficient level of skin adhesion, for instance, under conditions that simulate skin perspiration. Thus, a promising formulation has been obtained, which can be further used in preclinical and clinical studies and implemented into stump care practice for patients after lower limb amputations.