Optimisation of the composition of safe dental gel with IL-1β antagonist for the treatment of inflammatory periodontal diseases

Abstract

Aim. The study aims to develop the composition of the oromucosal gel with the IL-1β interleukin antagonist for complex treatment of inflammatory periodontal diseases. Materials and methods. Experimental studies were conducted based on the Department of Medicines Technology of Zaporizhzhia State Medical and Pharmaceutical University and the Training Medical and Laboratory Center of Zaporizhzhia State Medical and Pharmaceutical University of the Ministry of Health of Ukraine. As an active component, in the recipe of oromucosal gel, used antagonist of the interleukin IL-1B. Excipients: D-panthenol (the plasticizer), carboxymethylcellulose sodium salt (the viscosity modifier and mucoadhesive component), Tween-80 (the enhancer absorption), benzalkonium chloride (the preservative), sodium hydrophosphate + citric acid (the phosphate buffer solution), purified water. The experiments used existing and auxiliary ingredients of pharmaceutical purity, which were obtained from Sinbias LLC, Istok-Plus LLC, LLC “Mobile Medical”. For the design of the experiment, the methodology of the response surface (Box-Behnken Design) is used: Na CMC, Tween-80, D-panthenol; and four answers: pH, viscosity test, system type, mucoadhesive properties. Research methods: rheological research (viscosity test, amplitude test, frequency test, mucoadhesive test, thixotropy test) performed in oscillation mode on the modular compact Rheometer Anton Paar MCR 302 (CP50-1 SN71317), which, compared to cylindrical devices, requires a much smaller amount of gel sample and allows the planned tests in the oscillation mode, the temperature in the experiments was provided with a built-in thermostat (Peltier Temperature Control, C-PTD 200). Pharmaco-toxicological studies were conducted on 46 white outbred rats of both sexes, weighing 160–180 grams, which were received from Vivarium by the Institute of Pharmacology and Toxicology. The studies were performed on enough animals, all manipulations were carried out by the provisions on the use of animals in biomedical experiments. The results of the study were calculated using the standard statistical package of the Statistica for Windows 13 (StatSoft Inc., No. JPZ804I382130ARCN10-J), as well as SPSS 16.0, Microsoft Office Excel 2003. Results. According to the design of the experiment, it is established that the components of the system do not change the value of pH in experimental oromucosal gels (6.5500 ± 0.0334). The Anova for Quadratic Model statistical analysis data certify the significant impact of Na CMC, and Tween-80 factors on the viscous characteristics of oromucosal gels (F-value > p-value). Comparison of mucoadhesive characteristics of the studied samples of oromucosal gels was made using dynamic mechanical analysis and the results of statistical analysis of ANOVA for Quadratic Model highlight the significant influence of Na CMC, D-panthenol, Tween-80. Optimized oromucosal gel test data is obtained that its structure is restored after the applied effort, namely the restoration of the structure after 10 seconds occurs by 69.5 %, after 30 s by 76.1 %, after 180 s by 85.4 %, after 180 s which allows to predict the stability of the dosage form, both after manufacture and after use. Conclusions. The composition of the oromucosal gel of anti-inflammatory action with the IL-1β interleukin antagonist for the complex treatment of inflammatory diseases of periodontal is developed. The optimized composition of the oromucosal gel obtained has satisfactory performance of kinetic stability and thixotropic properties. The developed gel for dentistry meets all the requirements for harmlessness and safety for dosage forms of this group toxicity, lack of local irritant and allergic action.