EXCIPIENTS SELECTION AND CHARACTERIZATION FOR «RALITIN» GEL FOR ORAL ADMINISTRATION

The results of the investigation on the excipients selection for "Ralitin" gel for oral administration containing Matricaria flowers extractives (sum of flavonoids, essential oil) are presented in the article. The extractive was obtained using previously developed ultrasonic extraction technology. Gel compositions of the extractive with sodium carboxymethyl cellulose (Na-CMC), carboxymethyl cellulose (CMC), agar, carbomer, xanthan gum, gum arabic, apple pectin and mixtures thereof (Na-CMC - gum arabic, CMC - gum arabic, apple pectin - agar, xanthan gum - gum arabic) were studied. Studies on the selection of flavouring agents (orange, raspberry, banana, coconut) and commercially available sweeteners containing sodium saccharinate, sodium cyclamate, fructose, stevioside, stevia leaf extract, inulin, sucralose, and erythritol were carried out. Use of citric acid in the gel compositions at various concentrations as an acidulant and a pH regulator was investigated. The appearance, pH 5% aqueous solution, stability at elevated temperature (40 °C), rheological characteristics: dynamic viscosity (at a given shear rate of 50 s^-1) and viscosity vs. shear rate (the shear rate measurement range was between 10 s^-1 and 200 s^-1 and vice versa) were evaluated for the gel compositions. The organoleptic characteristics of the gel compositions were evaluated using the profile method and the evaluation method with letter and numerical indexes by I. A. Egorov. The stability, aggregative stability, rheological characteristics, flavonoids release ("Dissolution" test), taste profile were determined for the developed gel composition for oral administration. The aggregative stability of "Ralitin" gel was studied under conditions of natural storage (20 ºС) and at elevated temperature (40 ºC). It was established that the value of the kinetic stability coefficient of the gel samples did not change during 6 months of storage and remained equal to 0, which allows considering the system as aggregatively stable. In examination of the sum of flavonoids release, it was found that about 90% of the total amount of flavonoids was released from "Ralitin" gel into the dissolution medium during the first 5 minutes. In studying stability of the gel during storage by the "accelerated aging" method, it was established that the obtained gel is stable during the entire experimental shelf life (2 years). "Ralitin" gel on the basis of Matricaria flowers extractive contains Na-CMC as a gelation agent, sorbic acid as a preservative, and flavouring agents - sucralose with inulin, banana flavour, and citric acid. Thus, the excipients selection for the formulation of "Ralitin" gel for oral administration has been carried out. Rheological characteristics, dissolution profile and organoleptic properties of the resulting gel are acceptable.

gel for oral administration, formulation, Matricaria flowers, flavonoids, gelation agent, flavouring agents, taste profile

1. Anurova M. N., Bahrushina E. O., Demina N. B. Design of the composition and technology of long-acting oral nimesulide gel // Pharmacy. 2016. № 6. P. 30-34.

2. Anurova M.N., Bahrushina E.O., Demina N.B. The problem of taste masking of drugs // Drug Development & Registration. 2015. № 13. P. 64-73.

3. Anurova M. N., Bahrushina E. O., Krechetov S. P. Study of the matrix structure influence on the rheological characteristics of nimesulide oral gel experimental samples // Drug Development & Registration. 2016. № 4 (17). P. 98-104.

4. Bahrushina E. O., Anurova M. N. The development of the ibuprofen oral gel with plolonged release on the basis of composite delivery polymer polymer // Health and education in the twenty-first century. 2016. V. 18. № 5. P. 117-120.

5. Tastes and flovours - dissonance and consonance. Available at: http://foodinnovation.ru/articles/7921.html (accessed 14.01.2018).

6. State register of medicines. Available at: http://grls.rosminzdrav.ru/ (accessed 18.01.2018).

7. OFS.1.1.0013.15. Statistical processing of the results of a chemical experiment // State Pharmacopoeia of the Russian Federation. XIII ed. V. 1. - М., 2015. P. 235-264.

8. Dmitriєvs’kij D. І., Nemjatih O. D., Osolodchenko T. P. Research of the activity of antimicrobial preservatives in a jelly with echinacea purpurea for children // Bulletin of Pharmacy. 2010. № 3(63). P. 26-29.

9. Zagorul’ko E. Ju., Teslev A. A. Gels for oral administration. Part 1. Medical products and dietary supplements (review) // Drug Development & Registration. 2017. № 3(20). С. 42-48.

10. Zagorul’ko E. Ju., Teslev A.A. Gels for oral administration. Part 2. Excipients (review) // Drug Development & Registration. 2017. № 4(21). P. 34-43.

11. Zagorul’ko E. Ju., Teslev A. A., Ozhigova M. G. Development and optimization of ultrasound extraction of the chamomile flowers (Chamomillae recutita flores) // Pharmacy & Pharmacology. 2018. № 6(2). С. 151-166.

12. Zaporozhs’ka S. M., Baranova I. I., Grubnik I. M. Development of the composition and technology of vitamin gel for children // Bulletin of pharmacy. 2009. № 1(59). С. 27-29.

13. Kuznecov A. V., Kuznecov A. A. Taste corrigents in the manufacture of drugs // Pharmacy. 2011. № 2. P. 53-56.

14. Ljuk Je., Jager M. Preservatives in the food industry. Properties and applications. 3rd edition. - SPb.: GIORD, 2003. P. 127-133.

15. The monographs of the WHO on medicinal plants, widely used in the New Independent States. World Health Organization, 2010. Available at: http://apps.who.int/medicinedocs/documents/s17534ru/s17534ru.pdf#page=71 (accessed 22.02.2018).

16. Muca B., Zirko A., Djomin M. Carbopol™ polymers as functional gellants // Pharmaceutical technologies and packaging. 2017. № 2. С. 30-33.

17. The register of products that have passed state registration (issued by the Federal Service, including the Office). Available at: http://fp.crc.ru/gosregfr/?type=list (accessed 20.01.2018).

18. Sycheva O. V., Konoplev V. I., Veselova M. V. Increase in the accuracy of organoleptic evaluation // Achievements of science and technology of the agroindustrial complex. 2010. № 12. P. 79-80.

19. Tencova A. I., Azhgihin I. S. Dosage form and therapeutic efficacy of drugs (introduction to biopharmaceutics). - M.: Medicina, 1974. 335 p..

20. Tencova A. I., Aljushin M. T. Polymers in pharmacy. - M.: Medicina. 1985. 256 p..

21. Tencova A. I., Greckij V. M. Modern aspects of research and production of ointments. - M.: Medicina. 1980. 192 p..

22. Usenbaeva B., Ivanova L. A., Prjanishnikova N. T. i dr. Dosage form of trimecaine and pyromecaine based on aqueous sodium-carboxymethylcellulose gels // Pharmacy. 1985. № 6. P. 29-32.

23. Chueshov V. I. Industrial technology of medicines. V. 2. - Harkov: MTK-Kniga; NFAU. 2002. 716 p.

24. Chamomile. Kooperation Phytopharmaka. Available at: http://www.koop-phyto.org/on/medicinal.-plants/chamomile.php (accessed 22.02.2018).

25. Fleming T. Physician’s Desk Reference for Herbal Medicines. - Montvale: Medical Economics Company, 2000. 858 p.

26. Franke R., Schilcher H. Chamomile. Industrial Profiles. - Florida: CRC Press, 2005. 279 p.

27. Harrington E. C. The desirability function // Industrial Quality Control. 1965. V. 21. № 10. Р. 494-498.

28. Katdare A., Chaubal M. V. Excipient Development for Pharmaceutical, Biotechnology, and Drug Delivery Systems. - New York, London: Informa Healthcare USA, 2006. 452 p.

29. Moschakis T. Microrheology and particle tracking in food gels and emulsions // Current Opinion in Colloid & Interface Science. 2013. V. 18. P. 311-323.

30. Nazir A., Asghar A., Aslam Maan A. Advances in Food Rheology and its Applications. Chapter 13. Food Gels: Gelling Process and New Applications. 2017. P. 335-353.

31. Phillips G. O., Williams P. А. Handbook of Hydrocolloids, 2nd еd. - UK: Woodhead Publishing, 2009. 948 p.

32. Satyanarayana D. A., Kulkarni P. K., Shivakumar H. G. Gels and jellies as a dosage form for dysphagia patients: a review // Current Drug Therapy. 2011. V. 6. P. 79-86.

33. Shayne Cox Gad. Pharmaceutical Manufacturing Handbook. Production and Processes. - New Jersey: John Wiley & Sons. 2008. 1370 p.