Development of Composition and Technologies of Dental Gel of Meloxicam

BACKGROUND: Dental gels have several advantages over other oral dosage forms. Being a viscoplastic dosage form, the gel, when applied to the damaged area of the gum or mucous membrane, creates a protective film, preventing mechanical irritation, and providing a localized effect of the drug components. AIM: The aim of this work was to develop the composition and technology of the dental gel of meloxicam, the study of the main technological and consumer characteristics, as well as the local irritating effect of the dosage form. METHODS: Dental gels were prepared using purified water, alcohol, glycerol, and buckthorn oil as solvents, gelling agents used were: Hydroxyethylcellulose Natrosol® 250 HHX Pharm, Carbopol® 974P NF Polymer, and solubilizer Poloxamer 407 (Lutrol® F 127). The bioadhesive component and Noveon® Polycarbophil component were used for dental gel preparation. Aspartame was used as sweetener. Menthol and ascorbic acid were used to correct the organoleptic properties of the pharmaceutical composition. The formulated dental gel of meloxicam at a concentration of 7.5% was evaluated for organoleptic properties, pH, rheological characteristics, bioadhesive properties, and stability under the accelerated aging period. The in vivo local irritant effect was evaluated using ten rabbits by cutaneous, subcutaneous, subconjunctival administration, as well as application to the upper palate. RESULTS: Based on the results of studying technological and organoleptic properties, the optimal composition based on the Natrosol® 250 HHX hydroxyethylcellulose gelling agent, glycerol solvent, and purified water in the ratio 1/5 was selected, the composition contains Noveon® bioadhesive in an amount of 2%. The composition has good taste, pH close to pH of saliva has high bioadhesive properties, satisfactory rheological characteristics. The shelf life of the experimental series by accelerated aging was 2 years. The selected composition does not have a local irritant effect. CONCLUSION: A new dosage form of meloxicam was developed – a gel for use in dental practice

THE DEVELOPMENT AND STUDY OF THE TOXICITY OF SUPPOSITORIES WITH A MODIFIED SUBSTANCE OF INTERFERON ALFA-2B

Objective: To develop a stable composition with the substance of PEGylated interferon alfa-2b, to study technological and biopharmaceutical characteristics of the dosage form, and to conduct preclinical studies on the chronic toxicity and local irritating effect. Methods: Solid fats Witepsol® H15, Witepsol® W 35, Suppocire® BS2X, and Suppocire® BM brands were used as the suppository bases. Polysorbate 80 was used as an emulsifier. Citric acid, ascorbic acid, sodium tetraborate, lactic acid, ethylenediaminetetetraacetic acid, tocopherol acetate was also introduced into the experimental samples. Fourteen experimental samples were screened for biological and technological indicators. Preclinical studies were performed for the optimal composition on the indicators of chronic toxicity and local irritant effect. Results: The study examined the cytotoxic effects on the Vero cell line of selected suppository bases and excipients, namely, pH regulators and antioxidants. With excipients that did not have cytotoxicity we obtained suppository compositions with the following quality indicators: cytotoxicity, specific activity of interferon, time of complete deformation of suppositories and their melting temperature. A total of 14 compositions were studied, of which 5 were selected on the basis of the results for the study of stability. Only one composition turned out to be stable for the time studied. Conclusion: The most stable in terms of “specific activity” was sample 7, its composition: Witepsol® H15 / W35 70/30, polysorbate-80 0.15%, ethylenediaminetetraacetic acid (EDTA) 0.15%, sodium tetraborate 0.15%, tocopherol acetate 3.0%. Preclinical studies, that showed the absence of chronic toxicity and local irritant effect, were performed for this composition

DERMATOLOGIC GELS SPREADABILITY MEASURING METHODS COMPARATIVE STUDY

Objective. The main objective of our study is the comprehensive analysis and characterization of the existing spreadability evaluation strategies, the comparison of the obtained results reproducibility and convergence through the example of the 9 most widely used dermatological gels. Methods. Dolobene®, Flucinar®, Ketorol®, Contractubex®, Dr. Theiss Venen gel®, Solcoseryl®, Deep Relief®, Hepatrombin® pharmacopoeia gel samples were analyzed using parallel-plate, “slip and drag”, and viscometry methods. Analysis was performed in flow mode at 32 ± 0.2 °C, over shear rates ranging from 0 to 350 s−1, increasing over a period of 120 s, and was maintained at the superior limit for 10 s and then decreased during the same period. At least 5 replicates of each sample were evaluated, and the upward flow curves were fitted using the Casson mathematical model. Results. Solcoseryl® and Dolobene® showed the best spreadability in the parallel-plate method (3115.66±50.00 and 3316.63±50.00, respectively); Contractubex® and Dolobene showed the best spreadability in the “slip and drag” test (73.46±0.5 and 18.32±0.5, respectively); Solcoseryl® and Contractubex® showed the best spreadability in the viscometry test (43.86±0.5 and 76.92±0.5, respectively). Conclusion. This study analyzed the existing methods for determining the spreadability using commercially available samples of the dermatological gels as examples. The viscometric and the "Slip and drag" methods use different characteristics of spreadability, giving a complex evaluation of the measured parameter in vitro. Therefore, the combination of these two methods has the greatest prospects for reliable determination of this indicator

Modification of Taxifolin Properties by Spray Drying

Taxifolin is known as an active pharmaceutical ingredient (API) and food supplement due to its high antioxidant activity, multiple pharmacological effects, and good safety profile. Previously, taxifolin spheres (TS) were obtained from industrially produced API taxifolin in Russia (RT). In our work, we perform a pharmaceutical analysis of this new taxifolin material versus RT. TS is an amorphous material; however, it is stable without the polymer carrier, as confirmed by Fourier transform infrared spectroscopy. Both RT and TS demonstrate high safety profiles and are assigned to Class 1 of the Biopharmaceutical Classification System based on the results of experiments with MDCK cells. The water solubility of the new taxifolin form was 2.225 times higher compared with RT. Hausner ratios for RT and TS were 1.421 and 1.219, respectively, while Carr indices were 29.63% and 19.00%, respectively. Additionally, TS demonstrated sustained release from tablets compared with RT: the half-life values of tablets were 14.56 min and 20.63 min for RT and TS, respectively. Thus, TS may be a promising object for developing oral antiseptics in the form of orally dispersed tablets with sustained release patterns because of its anti-inflammatory, -protozoal, and -viral activities

Modification of Taxifolin Properties by Spray Drying

Taxifolin is known as an active pharmaceutical ingredient (API) and food supplement due to its high antioxidant activity, multiple pharmacological effects, and good safety profile. Previously, taxifolin spheres (TS) were obtained from industrially produced API taxifolin in Russia (RT). In our work, we perform a pharmaceutical analysis of this new taxifolin material versus RT. TS is an amorphous material; however, it is stable without the polymer carrier, as confirmed by Fourier transform infrared spectroscopy. Both RT and TS demonstrate high safety profiles and are assigned to Class 1 of the Biopharmaceutical Classification System based on the results of experiments with MDCK cells. The water solubility of the new taxifolin form was 2.225 times higher compared with RT. Hausner ratios for RT and TS were 1.421 and 1.219, respectively, while Carr indices were 29.63% and 19.00%, respectively. Additionally, TS demonstrated sustained release from tablets compared with RT: the half-life values of tablets were 14.56 min and 20.63 min for RT and TS, respectively. Thus, TS may be a promising object for developing oral antiseptics in the form of orally dispersed tablets with sustained release patterns because of its anti-inflammatory, -protozoal, and -viral activities