JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2020, 69(2):90-99 | DOI: 10.36290/csf.2020.014

Formulation and technology development of vaginal pessaries with probiotic activity

Zhanna Polova1,*, Svitlana Aleinyk1, Aurelii Kazak2
1 O. O. Bogomolets National Medical University, Department of Pharmacy and Industrial Technology of Drugs, Kiev, Ukraine
2 O. O. Bogomolets National Medical University, Department of obstetrics and gynecology № 1, Kiev, Ukraine, City Clinical Hospital № 18

Lactobacilli use in treatment and prevention of the vaginal microflora disorders, such as bacterial vaginosis and vulvovaginal candidiasis, is highly promising. The objective of this study was is to develop formulation and technology of the extemporal Lactobacillus casei (L. casei) ІМВ В-7280-containing medicinal product in the form of vaginal pessaries.
The quality control parameters were defined in accordance with the State Pharmacopeia of Ukraine (2nd edition) and included appearance, uniformity of texture, uniformity of mass and disintegration test. Lactobacilli assay was determined after preparation and within the storage period. Thus, feasible formulation and technology were selected for vaginal pessaries with an expected 6-month shelf life. The results of the hereby described research will be used for technological instruction development for extemporaneous vaginal pessaries with defined probiotic activity.

Keywords: vaginal pessaries; Lactobacilli; vaginal dysbiosis

Received: December 19, 2019; Accepted: March 3, 2020; Published: February 1, 2020  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Polova Z, Aleinyk S, Kazak A. Formulation and technology development of vaginal pessaries with probiotic activity. Čes. slov. farm. 2020;69(2):90-99. doi: 10.36290/csf.2020.014.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    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 Go to original source...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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 Go to original source...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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. Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source... Go to PubMed...
    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 Go to original source...
    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 Go to original source... Go to PubMed...
    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.

    Return to the content


    Czech and Slovak Pharmacy

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.