The dissertation is devoted to a comprehensive study of the development, standardization, and risk management of invasive medical devices for rectal use containing biologically active substances of plant origin. The research investigates the physicochemical, pharmacotechnological, and biological properties of products with a combined composition, as well as their compliance with current international standards and regulatory requirements.
Current trends in the development of rectal medical devices with plant extracts are analyzed, including the challenges in distinguishing between medical devices and medicinal products. The importance of combining in vitro and in vivo methods for a comprehensive safety assessment is emphasized. The properties of extracts from saw palmetto, lovage root, and calendula, obtained by supercritical CO₂ extraction, were studied, along with suppository bases (cocoa butter, Suppocire® AML, Witepsol® H15, polyethylene glycols). Quality control methods for suppositories included assessments of uniformity, breaking strength, melting and disintegration temperatures, active ingredient content, and microbiological purity. Cytotoxicity was evaluated using the MTT assay on cell cultures. Statistical analysis was performed using Student’s t-test and ANOVA. The optimal suppository formulation containing extracts with anti-inflammatory, antiandrogenic, and antioxidant activities was determined. The influence of active substance combinations on physicochemical characteristics, stability, and uniformity of distribution was explored. Auxiliary components were selected to ensure technological stability and effective delivery. The suppositories were found to be non-cytotoxic, non-sensitizing, and non-irritating. In experiments on a chronic inflammation model, pronounced therapeutic efficacy was demonstrated: reduction of edema and inflammatory response, improved microcirculation, antioxidant activity, and alleviation of pain. Compared to traditional dosage forms, rectal suppositories exhibited fewer side effects and provided localized action. The study also presents a risk management model in accordance with ISO 14971, covering the identification, assessment, and mitigation of risks associated with raw material variability, potential allergenicity, and interactions with sensitive tissues. Quality control measures are proposed at all stages of production. The proposed approaches to development, standardization, and risk management contribute to improving chronic prostatitis therapy and integrating Ukrainian manufacturers into the international market. The recommendations of this study may be used by regulatory authorities and manufacturers to enhance the processes of development, conformity assessment, and market introduction of medical devices. Thus, the conducted research lays the foundation for the further development of innovative medical devices that combine high efficacy with safety and meet the highest standards of modern medicine.
