Formulace a technologický vývoj vaginálních globulí s probiotickou aktivitou

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Autoři: Zhanna Polova ¹; Svitlana Aleinyk ¹; Aurelii Kazak ²
Působiště autorů: O. O. Bogomolets National Medical University, Department of Pharmacy and Industrial Technology of Drugs ¹; O. O. Bogomolets National Medical University, Department of obstetrics and gynecology № 1, Kiev, Ukraine, City Clinical Hospital № 18 ²
Vyšlo v časopise: Čes. slov. Farm., 2020; 69, 90-99
Kategorie: Původní článek

Souhrn

Použití laktobacilů při léčbě a prevenci poruch vaginální mikroflóry, jako je bakteriální vaginóza a vulvovaginální kandidóza, je velmi slibné. Cílem této studie bylo optimalizovat složení a technologii v současné době vyvíjeného léčivého přípravku ІМВ 72-7280 ve formě vaginálních globulí obsahujícího Lactobacillus casei (L. casei).

Parametry kontroly kvality byly definovány v souladu se Státním lékopisem Ukrajiny (2. vydání) a zahrnovaly posouzení vzhledu, stejnoměrnost textury, hmotnostní stejnoměrnost a zkoušku rozpadavosti. Obsah laktobacilů byl hodnocen po přípravě a během doby skladování. V rámci studie bylo vybráno vhodné složení a technologie pro přípravu vaginálních globulí s očekávanou skladovací dobou 6 měsíců. Výsledky popsané studie budou použity pro vývoj technologických instrukcí pro extemporózní vaginální pesary s definovanou probiotickou aktivitou.

Klíčová slova:

vaginální globule – Lactobacilli – vaginální dysbióza

Zdroje

1. Mastromarino P., Vitali B., Mosca L. Bacterial vaginosis, a review on clinical trials with probiotics. New Microbiol. 2013; 36(3), 229–238.

2. Kusuma Naik, Avinash, H. Nusrat, L. Krishna, Ravi Kumar. An RCT for efficacy of oral probiotics in treatment of cases with symptomatic white discharge per vagina in rural population. Journal of SAFOG 2012; 4(3), 126–129. doi:10.5005/jp-journals-10006-1193

3. Marcotte H., Krogh Andersen K., Lin Y., Zuo F., Zeng Z., Larsson P. G., Brandsborg E., Brønstad G., Hammarström L. Characterization and complete genome sequences of L. rhamnosus DSM 14870 and L. gasseri DSM 14869 contained in the EcoVag^® probiotic vaginal capsules. Microbiol. Res. 2017; 205, 88–98. doi:10.1016/j.micres.2017.08.003

4. Tomusiak A., Strus M., Heczko P., Adamski P., Stefański G., Mikołajczyk-Cichońska A., Suda-Szczurek M. Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria, a multicenter, randomized, double-blind, and placebo-controlled trial. Drug Des. Devel. Ther. 2015; 9, 5345–5354. doi:10.2147/DDDT.S89214

5. Mastromarino P., Brigidi P., Macchia S., Maggi L., Pirovano F., Trinchieri V., Conte U., Matteuzzi D. Characterization and selection of vaginal Lactobacillus strains for the preparation of vaginal tablets. J. Appl. Microbiol. 2002; 93(5), 884–893.

6. Powell A. M., Nyirjesy P. Recurrent vulvovaginitis. Best Pract. Res. Clin. Obstet. Gynaecol. 2014; 28(7), 967–976. doi:10.1016/j.bpobgyn.2014.07.006

7. Bertuccini L., Russo R., Iosi F., Superti F. Effects of Lactobacillus rhamnosus and Lactobacillus acidophilus on bacterial vaginal pathogens. Int. J. Immunopathol. Pharmacol. 2017; 30(2), 163–167. doi:10.1177/0394632017697987

8. Fuochi V., Cardile V., Petronio G., Furneri P. M. Biological properties and production of bacteriocins-like-inhibitory substances by Lactobacillus sp. strains from human vagina. J. Appl. Microbiol. 2019; 126(5), 1541–1550. doi:10.1111/jam.14164

9. Pendharkar S., Brandsborg E., Hammarström L., Marcotte H., Larsson P. G. Vaginal colonisation by probiotic lactobacilli and clinical outcome in women conventionally treated for bacterial vaginosis and yeast infection. BMC Infect. Dis. 2015; 3(15), 255. doi:10.1186/s12879-015-0971-3

10. Gaspar C., Donders G. G., Palmeira-de-Oliveira R., Queiroz J. A., Tomaz C., Martinez-de-Oliveira J., Palmeira-de-Oliveira A. Bacteriocin production of the probiotic Lactobacillus acidophilus KS400. AMB Express 2018; 8(1), 153. doi:10.1186/s13568-018-0679-z

11. Petricevic L., Witt A. The role of Lactobacillus casei rhamnosus Lcr35 in restoring the normal vaginal flora after antibiotic treatment of bacterial vaginosis. BJOG 2008; 115(11), 1369–1374. doi:10.1111/j.1471-0528.2008.01882.x

12. Neut C., Verrière F., Nelis H. J., Coenye T. Topical treatment of infectious vaginitis, effects of antibiotic, antifungal and antiseptic drugs on the growth of normal vaginal Lactobacillus strains. Open Journal of Obstetrics and Gynecology 2015; 5(3), 173–180 doi:10.4236/ojog.2015.53024

13. Marcotte H., Krogh Andersen K., Lin Y., Zuo F., Zeng Z., Larsson P. G., Brandsborg E., Brønstad G., Hammarström L. Characterization and complete genome sequences of L. rhamnosus DSM 14870 and L. gasseri DSM 14869 contained in the EcoVag^® probiotic vaginal capsules. Microbiol. Res. 2017; 205, 88–98. doi:10.1016/j.micres.2017.08.003

14. Hill D., Sugrue I., Tobin C., Hill C., Stanton C., Ross R. P. The Lactobacillus casei Group, History and Health Related Applications. Front. Microbiol. 2018; 9, 2107. doi:10.3389/fmicb.2018.02107

15. Melgaço A. C., Blohem Pessoa W. F., Freire H. P., Evangelista de Almeida M., Santos Barbosa M., Passos Rezende R., Timenetsky J., Miranda Marques L., Romano C. Potential of maintaining a healthy vaginal environment by two Lactobacillus strains isolated from cocoa fermentation. Biomed. Res. Int. 2018; 30, 7571954. doi:10.1155/2018/7571954

16. Sobel J. D., Schneider J., Kaye D., Levison M. E. Adherence of bacteria to vaginal epithelial cells at various times in the menstrual cycle. Infect Immun. 1981; 32(1), 194–197.

17. Borges S., Silva J., Teixeira P. The role of lactobacilli and probiotics in maintaining vaginal health. Arch. Gynecol. Obstet. 2014; 289(3), 479–489. doi:10.1007/s00404-013-3064-9

18. Laue C., Papazova E., Liesegang A., Pannenbeckers A., Arendarski P., Linnerth B., Domig K. J., Kneifel W., Petricevic L., Schrezenmeir J. Effect of a yoghurt drink containing Lactobacillus strains on bacterial vaginosis in women – a double-blind, randomised, controlled clinical pilot trial. Benef. Microbes 2018; 9(1), 35–50. doi:10.3920/BM2017.0018

19. Homayouni A., Bastani P., Ziyadi S., Mohammad-Alizadeh-Charandabi S., Ghalibaf M., Mortazavian A. M., Mehrabany E. V. Effects of probiotics on the recurrence of bacterial vaginosis, a review. J. Low. Genit. Tract. Dis. 2014; 18(1), 79–86. doi:10.1097/LGT.0b013e31829156ec

20. Kumar N., Behera B., Sagiri S. S., Pal K., Ray S. S., Roy S. Bacterial vaginosis, Etiology and modalities of treatment – A brief note. J. Pharm. Bioallied. Sci. 2011; 3(4), 496–503. doi:10.4103/0975–7406.90102

21. Leyva-Gómez G., Prado-Audelo M. L. D., Ortega-Peña S., Mendoza-Muñoz N., Urbán-Morlán Z., González-Torres M., González-Del Carmen M., Figueroa-González G., Reyes-Hernández O. D., Cortés H. Modifications in Vaginal microbiota and their influence on drug release, challenges and opportunities. Pharmaceutics 2019; 11(5). pii:E217. doi:10.3390/pharmaceutics11050217

22. Balish E., Wagner R. D. Probiotic bacteria for prophylaxis and therapy of candidiasis. Rev. Iberoam. Micol. 1998; 15(4), 261–264.

23. Cadieux P., Burton J., Gardiner G., Braunstein I., Bruce A. W., Kang C. Y., Reid G. Lactobacillus strains and vaginal ecology. JAMA 2002; 287(15), 1940–1941.

24. Anukam K. C., Osazuwa E., Osemene G. I., Ehigiagbe F., Bruce A. W., Reid G. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis. Microbes Infect. 2006; 8(12–13), 2772–2776.

25. Mastromarino P., Macchia S., Meggiorini L., Trinchieri V., Mosca L., Perluigi M., Midulla C. Effectiveness of Lactobacillus-containing vaginal tablets in the treatment of symptomatic bacterial vaginosis. Clin. Microbiol. Infect. 2009; 15(1), 67–74. doi:10.1111/j.1469-0691.2008.02112.x

26. Parent D., Bossens M., Bayot D., Kirkpatrick C., Graf F., Wilkinson F. E., Kaiser R. R. Therapy of bacterial vaginosis using exogenously-applied Lactobacilli acidophili and a low dose of estriol, a placebo-controlled multicentric clinical trial. Arzneimittelforschung 1996; 46(1), 68–73.

27. Hallen A., Jarstrand C., Pahlson C. Treatment of bacterial vaginosis with lactobacilli. Sex Transm. Dis. 1992; 19(3), 146–148.

28. Ehrström S., Daroczy K., Rylander E., Samuelsson C., Johannesson U., Anzén B., Pahlson C. Lactic acid bacteria colonization and clinical outcome after probiotic supplementation in conventionally treated bacterial vaginosis and vulvovaginal candidiasis. Microbes Infect. 2010; 12(10), 691–699. doi:10.1016/j.micinf.2010.04.010

29. Maggi L., Mastromarino P., Macchia S., Brigidi P., Pirovano F., Matteuzzi D., Conte U. Technological and biological evaluation of tablets containing different strains of lactobacilli for vaginal administration. Eur. J. Pharm. Biopharm. 2000; 50(3), 389–395.

30. Burton J. P., Cadieux P. A., Reid G. Improved understanding of the bacterial vaginal microbiota of women before and after probiotic instillation. Appl. Environ Microbiol. 2003; 69(1), 97–101.

31. Eriksson K., Carlsson B., Forsum U., Larsson P. G. A double-blind treatment study of bacterial vaginosis with normal vaginal lactobacilli after an open treatment with vaginal clindamycin ovules. Acta Derm. Venereol. 2005; 85(1), 42–46.

32. Czaja C. A., Stapleton A. E., Yarova-Yarovaya Y., Stamm W. E. Phase I trial of a Lactobacillus crispatus vaginal suppository for prevention of recurrent urinary tract infection in women. Infect. Dis. Obstet. Gynecol. 2007; 2007, 35387. doi:10.1155/2007/35387

33. Drago L., de Vecchi E., Nicola L., Zucchetti E., Gismondo M. R., Vicariotto F. Activity of a Lactobacillus acidophilus-based douche for the treatment of bacterial vaginosis. J. Altern. Complement Med. 2007; 13(4), 435–438.

34. Kale V., Trivedi R., Muley P. Proposed design of a dissolution apparatus for vaginal formulations containing probiotics. Dissolution Technologies 2008; 15(2). doi:10.14227/DT150208P27

35. Larsson P. G., Stray-Pedersen B., Ryttig K. R., Larsen S. Human lactobacilli as supplementation of clindamycin to patients with bacterial vaginosis reduce the recurrence rate; a 6-month, double-blind, randomized, placebo-controlled study. BMC Womens Health 2008; 8, 3. doi:10.1186/1472-6874-8-3

36. Kaewnopparat S., Kaewnopparat N. Formulation and evaluation of vaginal suppositories containing Lactobacillus. International Scholarly and Scientific Research & Innovation 2009; 3(7), 117–120.

37. Rodrigues F., Maia M. J., Neves J., Sarmento B., Amaral M. H., Oliveira M. B. Vaginal suppositories containing Lactobacillus acidophilus, development and characterization. Drug Dev. Ind. Pharm. 2015; 41(9), 1518–1525. doi:10.3109/03639045.2014.963864

38. Falagas M., Betsi G. I., Athanasiou S. Probiotics for the treatment of women with bacterial vaginosis. Clin. Microbiol. Infect. 2007; 13(7), 657–664.

39. Ozkinay E., Terek M. C., Yayci M., Kaiser R., Grob P., Tuncay G. The effectiveness of live lactobacilli in combination with low dose oestriol (Gynoflor) to restore the vaginal flora after treatment of vaginal infections. BJOG 2005; 112(2), 234–240.

40. Uehara S., Monden K., Nomoto K., Seno Y., Kariyama R., Kumon H. A pilot study evaluating the safety and effectiveness of Lactobacillus vaginal suppositories in patients with recurrent urinary tract infection. Int. J. Antimicrob. Agents 2006; 28(1), S30–34.

41. Kale V. V., Trivedi R. V., Wate S. P., Bhusari K. P. Development and evaluation of a suppository formulation containing Lactobacillus and its application in vaginal diseases. Ann NY Acad. Sci. 2005; 1056, 359–365.

42. Ya W., Reifer C., Miller L. E. Efficacy of vaginal probiotic capsules for recurrent bacterial vaginosis, a double-blind, randomized, placebo-controlled study. Am. J. Obstet. Gynecol. 2010; 203(2), 120.e1–6. doi:10.1016/j.ajog.2010.05.023

43. Kaewsrichan J., Chandarajoti K., Kaewnopparat S., Kaewnopparat N.. Evaluation of Lactobacilli containing suppository formulation for probiotic use. Mahidol University Journal of Pharm. Sci. 2007; 34(1–4), 1–8.

44. Fazeli M. R., Toliyat T., Samadi N., Hajjaran S., Jamalifar H. Viability of lactobacillus acidophilus in various vaginal tablet formulations. DARU Journal of Pharmaceutical Sciences 2006; 14(4), 172–178.

45. Ashok V. R. Manoj Kumar, D. Murali, Arkendu Chatterjee. A review on vaginal routeas a systemic drug delivery. https://www.researchgate.net/publication/224318371_A_review_on_vaginal_route_as_a_systemic_drug_delivery (18. 10. 2019).

46. Ham A. S., Buckheit R. W. Jr. Designing and developing suppository formulations for anti-HIV drug delivery. Ther. Deliv. 2017; 8(9), 805–817. doi:10.4155/tde–2017–0056

47. Zujkina S. V. Stan ekstemporal`noyi receptury` Ukrayiny` ta problemy` s`ogodennya. Zb. nauk. pracz` spivrobit. NMAPO imeni P. L. Shupy`ka 2018; 32, 294–307.

48. Patent Ukrainy na korysnu model UA № 98881, C12N 1/00 vid 12.05.2015, biul. № 9.

49. Patent Ukrainy na vynakhid UA № 93133, C12N 1/20 vid 10.01.2011, biul. № 1.

50. Ham A. S., Buckheit R. W. Jr. Designing and developing suppository formulations for anti-HIV drug delivery. Ther. Deliv. 2017; 8(9), 805–817. doi:10.4155/tde-2017-0056

51. Rowe R. C., Sheskey P. J., Quinn M. E. Handbook of pharmaceutical excipients. London: Pharmaceutical Press 2009; 517–521.

52. Jankowski A., Dyja R., Sarecka-Hujar B. Dermal and transdermal delivery of active substances from semisolid bases. Indian. J. Pharm. Sci. 2017; 79(4), 488–500. doi:10.4172/pharmaceutical-sciences.1000255

53. Zárate G., Juárez Tomás M. S., Nader-Macias M. E. Effect of some pharmaceutical excipients on the survival of probiotic vaginal lactobacilli. Canadian Journal of Microbiology 2005; 51(6), 483–489. doi:10.1139/w05–031

54. Reitermayer D., Kafka T. A., Lenz Ch. A., Vogel R. F. Interrelation between Tween and the membrane properties and high pressure tolerance of Lactobacillus plantarum. BMC Microbiology 2018; 18(1), 72. doi:10.1186/s12866-018-1203-y

55. Malheiros P. S., Sant’Anna V., Todorov S. D., Franco B. D. G. M. Optimization of growth and bacteriocin production by lactobacillus sakei subsp. Sakei 2a. Brazilian Journal of Microbiology, 2015; 46(3), 825–834. doi:10.1590/S1517–838246320140279

56. Coelho L. F., Lima C. J. B., Rodovalho C. M., Bernardo M. P., Contiero J. Lactic acid production by new Lactobacillus plantarum LMISM6 grown in molasses, optimization of medium composition. Braz. J. Chem. Eng. 2011; 28(1). doi:10.1590/S0104-66322011000100004

57. Realdon N., Dal Zotto M., Morpurgo M., Franceschinis E. Effects of surfactant characteristics on drug availability from suppositories. Pharmazie 2008; 63(6), 459–463. doi:10.1691/ph.2008.7378

58. Hanaee J., Javadzadeh Y., Taftachi S., Farid D., Nokhodchi A. The role of various surfactants on the release of salbutamol from suppositories. Farmaco 2004; 59(11), 903–906. doi:10.1016/j.farmac.2004.07.006

59. Kale V., Patil M., Yadav S. Preparation and evaluation of Novel Vaginal Pessaries of Lactobacilli. Int. J. Drug Dev. & Res. 2012; 4(3), 97–103.

60. Pashayan M. M. Formulation and investigation of vaginal double layer suppositories containing lactobacilli and herbal extracts. The New Armenian Medical Journal 2011; 2, 54–59.

61. Franceschinis E., Realdon N. Effect of the surfactant on the availability of piroxicam as a poorly hydrosoluble drug from suppositories. Pharmazie 2012; 67(1), 37–45. doi:10.1691/ph.2012.1092

62. Chale G. R., Jeughale A. S. Suppository, a review. World Journal of Pharmaceutical Research 2019; 8, 1968–1982.