Pharmaceutical development of complex wound-healing ointment for the needs of military medicine

Abstract

This article presents experimentally proved scientific-practical methods of developing modern vulnerary medical preparations in the form of an ointment with antibacterial, anti-inflammatory and anesthetic properties for the purposes of military medicine. In pursuit of the designated goals, the authors used modern methods of research: pharmacological-technological, physical-chemical, structural-mechanical and biological methods – for proving the compound of the combined ointment including ofloxacin, nimesulide and lidocaine. On the basis of the research conducted, we proved the content and rational technique of the complex antimicrobial ointment with anti-inflammatory and anesthetic effect using ofloxacin (0.05 g), nimesulide (1.0 g) and lidocaine (4.0 g). We experimentally established the optimal content of the main component of the ointment: emulsive base of mixture of Polyethylene Oxide-400 and Polyethylene Oxide-1500 (1 : 4) and a complex of emulsifiers of the first and the second generations – cetostearylic alcohol – 3%, monoglyceryl stearate – 5% at the constant concentration of paraffin oil – 20%, which involves a certain temperature regime during preparation, a sequence of introducing active pharmacological ingredients and adjuvants to the water and oil phases, frequency and duration of mixing. Physical-chemical tests of the ointment base determined the optimum concentration of glycerine as 5%, which encourages elimination of purulent discharge from damaged tissues, causing an anti-inflammatory effect and providing a prolonged, but milder dehydrating effect. The relation between physical-chemical, rheological, biopharmaceutical properties of the developed preparation and the concentration and method of introduction of the active pharmaceutical ingredients was theoretically and experimentally proven. We conducted pre-clinical studies (in vivo) for defining the therapeutic efficiency of the ofloxacin-nimesulide composition in the compound of the developed ointment for complex treatment of the wound process. We studied the specific activity (anti-alternative – model of standard tissue wounds in rats), which allowed us to establish the optimum concentration of nimesulide, which is 1%. Biopharmaceutical studies (in vitro method) determined the optimum method of introducing ofloxacin, nimesulide and lidocaine in the ointment base as a solution in dimethyl sulfoxide. To select an anesthetic substance for the ointment, the authors conducted a comparative study on the anesthetic effect of the anesthetics most widely available in Ukraine: novocaine, dicainum, lidocaine, trimecainum and pyromecainum. The research conducted on the time it took for the anesthetic effect to occur and on the duration and extent of the effect enabled us to select a 4% concentration of lidocaine anesthetic for the preparation. The choice of the temperature regime for the ointment’s preparation was proved. The in vitro method and rheological studies determined that the optimum temperature regime for the technological process of preparing the ointment on the emulsive base is 25–30 ºС. The development and introduction of the new combined ointment on a contemporary hydrophilic ointment base into practical pharmacy would lead to an enlargement in the nomenclature of the medical preparations used for local treatment of the purulent – necrotic phase of the wound process, which is relevant for pharmaceutical technology and global medical science and practice.

Keywords

• ofloxacin
• nimesulide
• lidocaine
• rheology
• wound process