Purtov O. Pharmaceutical development and investigation of liquid medicinal products with benzalconium chloride.

The thesis concerns complex investigations of some physicochemical and biopharmaceutical properties of water solutions of benzalconium chloride (BC) in comparison to some other cationic antiseptics as well as pharmaceutical development of two medicinal products in the form of topical solutions which contain BC at different concentrations. By the spin label method it has been shown that this is probably due to partial solubilization of PE by micelles and due to the formation salt between DSE and benzalconium cations, resulting an enhancement of hydrophobic properties of these cations and the micelles. It has been found by in vitro experiments that the spectrum of antimicrobial action of BC solutions expands, in particular regarding to gram-negative bacteria, and its efficiency enhances provided the influence of DSE and PE, which allows the use of BC in low concentrations and gives the advantages of BC solutions compared with medicinal products with other cationic antiseptics. Reducing the BC content in solutions (due to presence of DSE and PE) eliminates their irritating effect at skin applications as well as vaginal and urethral administration to experimental animals. According to the current methodology, the pharmaceutical development of two medicinal products with BC in the form of topical solutions has been carried out. The analytical procedures have been developed, their validation has been carried out and the quality attributes have been standardized. Physical and chemical properties of these products are studied as well as their biological properties are summarized. The primary packaging for these preparations has been chosen, the production process has been developed, the microbiological characteristics have been studied. The registration dossier for these drugs has been compiled, they are registered by the Ministry of Health of Ukraine and introduced into manufacture and medical practice.