Experimental Study of Antimicrobial Properties and Acute Toxicity of the Peo-based Combined Suppositories

Aim. The research of antimicrobial and toxicological parameters of a promising pharmaceutical composition with indole-3-carbinol and meloxicam in the form of rectal suppositories.Materials and methods. The research of antimicrobial activity was carried out in vitro by diffusion in nutrient agar in the modification of "holes" on the reference strains of common pathogens Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, Candida albicans.Adult rats were used for the study of acute toxicity. Suppository mass were administrated in the largest possible volume rectally or orally. The animals were periodically monitored according to the experimental plan – the assessment of physiological parameters before administration and after 6, 12, 18, 24 hours, at 3, 7 and 14 days. The animals were removed from experiment and necropsy provided after 1, 3, 7, and 14 days.Results. The sizes of zones of inhibition of the microorganisms growth were most significant (from 19.27±0.61 mm of E. coli to 40.80±0.42 mm of S. aureus) near sample of the combined composition suppository compared with other combination of active substances and excipients.During the observation of animals for 14 days and the study of internal organs after autopsy, deviations in physiological (weight, temperature, activity, respiratory rate) and macroscopic morphological indicators of animals from reference values were not detected.Conclusion. According to the results of microbiological studies, a moderate antimicrobial effect of suppositories of combined composition in relation to all the studied pathogens was revealed. The absence of manifestations of acute toxicity allows us to conclude that the pharmaceutical composition can be classified as practically non-toxic substances.The obtained results allow us to recommend a pharmaceutical composition with indole-3-carbinol and meloxicam on a polyethylene oxide basis in the form of suppositories for further preclinical studies of specific pharmacological effects as a prostate protective agent

Physico-chemical and Pharmaco-technological Research at a Substantiation of Rational Composition and Technology of Suppositories «Indoxam»

The development of new highly effective drugs in the form of rectal suppositories for the treatment of diseases of the prostate gland does not lose its relevance today, since the number of patients with these pathologies is increasing every year. These diseases adversely affect the physical, psychological health and quality of life of men in general.An important issue in the substantiation of the composition and development of the technology for the production of suppositories is the study of their physico-chemical and pharmaco-technological properties that directly affect their consumer qualities and the mode of the technological process.Aim of the work was the study of the physico-chemical and pharmaco-technological properties of the combined rectal suppositories "Indoxam" to select rational conditions of the technological process.Materials and methods. In order to substantiate the composition and technology of the combined rectal suppositories “Indoxam”, modern physicochemical (thermal analysis, rotational viscometry method) and pharmaco-technological (disintegration suppositories, resistance to degradation) studies were used according to the requirements of SPHU.Results. To select the optimal ratio of polyethylene oxides in the suppository base, the resistance of suppositories to destruction and the disintegration time of samples made with different amounts of PEO-1500 and PEO-400 were studied. To determine the optimal technology for the preparation of the drug, a study was made of the decomposition temperature of the API, which makes it possible to determine the temperature regimes for the preparation of suppositories and the introduction of active substances into the base without the risk of destroying the structure of substances and changing their pharmacological actions. Since, under the influence of mechanical, thermal, and other actions, several types of destruction undergo suppositories, their rheological characteristics are also investigated.Conclusions. The results of pharmaco-technological research allowed to substantiate the optimal ratio of polyethylene oxides in suppository basis. The conducted thermogravimetric analysis of API and suppositories «Indoxam» established the thermal stability of substances and the absence of chemical interaction between the components in the composition of rectal drug. According to the rheological characteristics, the system identified the thixotropy and the optimal pouring temperature of the suppository mas