Management of diabetic foot ulcers: a 25% lidocaine topical cream formulation design, physicochemical and microbiological assessments.

Background: Given the importance of surgical debridement in healing of diabetic foot ulcers, effective local anaesthesia is required to manage the related extreme pain. The pharmaceutical proprietary products currently available have low concentrations and do not exceed 5% w/w local anaesthetic. Objective: Formulation design of a lidocaine cream of 25% and assessment of the intrinsic stability. Methods: A cream pharmaceutical form was chosen for its ability to cross the skin barrier and effectively anaesthetise the skin. The choice of cream formula is based on changes in the size of the emulsions and resistance to physical stress. Stability tests were assessed over a 6-month period in terms of physical (evaluation of oil droplets), microbiological (germ count and identification, and preservative antimicrobial efficacy) and chemical parameters (content and pH). Results: Under the study conditions, the drug product displayed good physicochemical and microbiological stability for 6 months at 20°C and 40°C, and no degradation product was detected. Due to the systemic adverse effects of lidocaine, the pH stability guarantee the drug product tolerance along with very weak systemic passage. Conclusions: Given the good physicochemical and microbiological stability of the drug product over 6-month period, it has been made available to the clinical unit. An average of 250 patients per year benefit from the treatment with an excellent efficacy/tolerability ratio.

Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies.

The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA). To improve patient adherence to such treatments, combination therapies (polypill) are envisioned. Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC). The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis. A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited. No cocrystals of TIC and ASA have been found. The appearance of the eutectic liquid was linked with a clear onset of chemical instability of the two pharmaceuticals. The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites. Seven interaction products were observed by LC-HR-MSn linked to corresponding degradation products. The most important degradation pathway is N-dealkylation. In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.