Design and Development of Novel Herbal Suppository Formulation for Prostatitis Treatment
DOI:
https://doi.org/10.20535/ibb.2024.8.4.317124Keywords:
prostatitis, herbal suppositories, Witepsol® H15, anti-inflammatory activity, therapeutic formulationsAbstract
Background. Prostatitis is a common inflammatory condition of the prostate gland, often treated with antibiotics and anti-inflammatory drugs, which may have limited efficacy and side effects. Herbal therapies offer a promising alternative due to their natural anti-inflammatory properties.
Objective. This study aims to design, develop, and evaluate physicochemical, biopharmaceutical and microbiological properties of novel herbal suppository formulations for the treatment of prostatitis, optimizing their biopharmaceutical profiles.
Methods. Excipients were selected to form suppositories with herbal ingredients known for their anti-inflammatory effects, specifically lovage, saw palmetto, and calendula CO2 extracts. The formulations were assessed based on key quality parameters, including organoleptic characteristics, average mass, melting point, deformation time, disintegration time, microbiological purity, and pH, ensuring compliance with European Pharmacopoeia (Ph. Eur.) standards. Biopharmaceutical studies compared the release profiles of active compounds from different suppository bases.
Results. Suppositories based on Witepsol® H15 exhibited satisfactory organoleptic properties, appropriate melting points, and acceptable deformation and disintegration times. The pH levels were within the required range, and microbiological tests confirmed purity. Biopharmaceutical evaluations showed that Witepsol® H15 suppositories had the most appropriate release rates of active compounds compared to those made with other bases.
Conclusions. The novel herbal suppositories developed in this study show promise for managing prostatitis based on preliminary evaluations of their physicochemical, microbiological, and biopharmaceutical properties. Further clinical studies are required to confirm their efficacy and safety.
References
Krieger JN, Nyberg Jr L, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA. 1999 Jul 21;282(3):236-7. DOI: 10.1001/jama.282.3.236
Pendegast HJ, Leslie SW, Rosario DJ. Chronic Prostatitis and Chronic Pelvic Pain Syndrome in Men. StatPearls, 2024.
Davis NG, Silberman M. Acute Bacterial Prostatitis. StatPearls, 2023.
Weidner W, Wagenlehner FME, Marconi M, Pilatz A, Pantke KHP, Diemer T. Acute bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: andrological implications. Andrologia. 2008;40(2):105-12. DOI: 10.1111/j.1439-0272.2007.00828.x
Khattak AS, Raison N, Hawazie A, Khan A, Brunckhorst O, Ahmed K. Contemporary management of chronic prostatitis. Cureus. 2021 Dec 7;13(12):e20243. DOI: 10.7759/cureus.20243
Thakkinstian A, Attia J, Anothaisintawee T, Nickel JC. α‐blockers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome. BJU Int. 2012;110(7):1014-22. DOI: 10.1111/j.1464-410X.2012.11088.x
Franco JV, Turk T, Jung JH, Xiao Y-T, Iakhno S, Tirapegui FI, Garrote V, Vietto V. Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome. Cochrane Database Syst Rev. 2019 Oct 6;10(10):CD012552. DOI: 10.1002/14651858.CD012552.pub2
Widia F, Atmoko W, Agung NP, Rahardjo HE, Rasyid N, Birowo P, et al. The efficacy of antibiotic and alpha-blocker combination therapy versus antibiotic monotherapy in chronic prostatitis/chronic pelvic pain syndrome: A systematic review. Low Urin Tract Symptoms. 2023;15(4):107-15. DOI: 10.1111/luts.12477
Ishiguro H, Kawahara T. Nonsteroidal anti-inflammatory drugs and prostatic diseases. Biomed Res Int. 2014;2014:436123. DOI: 10.1155/2014/436123
Hochreiter WW. Anti-inflammatory therapies for chronic prostatitis. Eur Urol Suppl. 2003 Mar 1;2(2):30-3. DOI: 10.1016/s1569-9056(02)00198-7
Zhang K, Guo R-Q, Chen S-W, Chen B, Xue X-B, Chen S, et al. The efficacy and safety of Serenoa repens extract for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome: a multicenter, randomized, double-blind, placebo-controlled trial. World J Urol. 2021;39(9):3489-95. DOI: 10.1007/s00345-020-03577-2
Cai T, Mazzoli S, Bechi A, Addonisio P, Mondaini N, Pagliai RC, et al. Serenoa repens associated with Urtica dioica (ProstaMEV) and curcumin and quercitin (FlogMEV) extracts are able to improve the efficacy of prulifloxacin in bacterial prostatitis patients: results from a prospective randomised study. Int J Antimicrob Agents. 2009 Jun;33(6):549-53. DOI: 10.1016/j.ijantimicag.2008.11.012
Franco JV, Trivisonno L, Sgarbossa NJ, Alvez GA, Fieiras C, Escobar Liquitay CM, et al. Serenoa repens for the treatment of lower urinary tract symptoms due to benign prostatic enlargement. Cochrane Database Syst Rev. 2023 Jun 22;6(6):CD001423. DOI: 10.1002/14651858.CD001423.pub4
Stamatiou K, Pierris N. Serenoa repens extract additionally to quinolones in the treatment of chronic bacterial prostatitis. The preliminary results of a long term observational study. Arch Ital Urol Androl. 2013;85(4):190-6. DOI: 10.4081/aiua.2013.4.190
Assessment report on Serenoa repens (W. Bartram) Small, fructus. European Medicines Agency, 2015 Nov. Report No.: EMA/HMPC/137250/2013. Available from: https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-serenoa-repens-w-bartram-small-fructus_en.pdf
Morgia G, Russo GI, Urzì D, Privitera S, Castelli T, Favilla V, et al. A phase II, randomized, single-blinded, placebo-controlled clinical trial on the efficacy of Curcumina and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III. Arch Ital Urol Androl. 2017;89(2):110-3. DOI: 10.4081/aiua.2017.2.110
European Union Herbal Monograph on Calendula officinalis L., Flos. European Medicines Agency, 2018 Mar. Report No.: EMA/HMPC/437450/2017. Available from: https://www.ema.europa.eu/en/documents/herbal-monograph/final-european-union-herbal-monograph-calendula-officinalis-l-flos-revision-1_en.pdf
Popp M. Canephron for treatment of prostatitis. European Patent EP3206701A1, published 2017-08-23. Available from: https://patents.google.com/patent/EP3206701A1/en
Jakubczyk A, Złotek U, Szymanowska U, Rybczyńska-Tkaczyk K, Jęderka K, Lewicki S. In vitro antioxidant, anti-inflammatory, anti-metabolic syndrome, antimicrobial, and anticancer effect of phenolic acids isolated from fresh lovage leaves [Levisticum officinale Koch] elicited with jasmonic acid and yeast extract. Antioxidants (Basel). 2020 Jun 25;9(6):554. DOI: 10.3390/antiox9060554
Mohammadi M, Parvaneh E, Tolou Ghamari Z. Clinical investigation of Levisticum officinale (Lovage) effectiveness' in patients with cystinuria. Journal of Urology and Research. 2016;3(6):1071. Available from: https://www.jscimedcentral.com/jounal-article-info/Journal-of-Urology-and-Research/Clinical-Investigation-of--Levisticum-officinale-%28Lovage%29--Effectiveness%E2%80%99-in-Patients-with--Cystinuria-6545
Nausch B, Pace S, Pein H, Koeberle A, Rossi A, Künstle G, Werz O. The standardized herbal combination BNO 2103 contained in Canephron® N alleviates inflammatory pain in experimental cystitis and prostatitis. Phytomedicine. 2019 Jul;60:152987. DOI: 10.1016/j.phymed.2019.152987
Assessment report on Levisticum officinale Koch, radix. European Medicines Agency, 2012 Mar. Report No.: EMA/HMPC/524623/2011. Available from: https://www.ema.europa.eu/en/documents/herbal-report/draft-assessment-report-levisticum-officinale-koch-radix_en.pdf
Dmytrenko O, Lutsenko T, Dmytrenko A, Bespalova O. Assessment of efficiency and safety of phytocomposition with prostate-protective properties in the form of rectal suppositories. Nat Eng Sci. 2024 Oct 30;9(2):407-25. DOI: 10.28978/nesciences.1465276
Dmytrenko O, Arkhypova M, Starosyla D, Rybalko S, Gevorkyan M, Galkin A. Biological evaluation of medical devices in the form of suppositories for rectal and vaginal use. Innov Biosyst Bioeng. 2021;5(4):228-37. DOI: 10.20535/ibb.2021.5.4.249082
Galkin A, Komar A, Gorshunov Y, Besarab A, Soloviova V. New monoclonal antibodies to the prostate-specific antigen: obtaining and studying biological properties. J Microbiol Biotechnol Food Sci. 2019;9(3):573-7. DOI: 10.15414/jmbfs.2019/20.9.3.573-577
European Pharmacopoeia (Ph. Eur.) 11th Edition. EDQM. Available from: https://www.edqm.eu/en/european-pharmacopoeia-ph.-eur.-11th-edition
Lichtenthaler HK, Buschmann C. Chlorophylls and carotenoids: measurement and characterization by UV-VIS spectroscopy. Curr Protoc Food Anall Chem. 2001 Aug 1;1(1): F4.3.1-F4.3.8. DOI: 10.1002/0471142913.faf0403s01
Mishra P, Singh R, Kumari G, Kumari N, Verma AK. Formulation and evaluation of flax herbal suppositories. J Drug Deliv Therapeut. 2022 Jan 15;12(1):19-22. DOI: 10.22270/jddt.v12i1.5253
Ebrahimi F, Torbati M, Khoshbakht Z, Khodaie L. Application of herbal rectal suppositories beyond intestinal disorders in Persian medicine. Trad Med Res. 2019 Jan 1;4(3):160-72. DOI: 10.53388/TMR20190414115
Niwatananun K, Niwatananun W, Piyamongkol S, Hongwiset D, Ruengorn C, Koyratkoson K, et al. Clinical pilot study of rectal suppository containing combined extract of Cissus quadrangularis Linn. And Acmella paniculata (Wall ex. DC.) R. K. Jansen in acute hemorrhoids. Evid Based Complement Alternat Med. 2021 Nov 2;2021:5605323. DOI: 10.1155/2021/5605323
Ortega AB, Garcia AC, Szekely E, Škerget M, Knez Ž. Supercritical fluid extraction from Saw Palmetto berries at a pressure range between 300bar and 450bar. J Supercritical Fluids. 2017 Feb 1;120(part 1):132-9. DOI: 10.1016/j.supflu.2016.11.003
Idan A, Griffiths KA, Harwood DT, Seibel MJ, Turner L, Conway AJ, et al. Long-term effects of dihydrotestosterone treatment on prostate growth in healthy, middle-aged men without prostate disease: a randomized, placebo-controlled trial. Ann Intern Med. 2010 Nov 16;153(10):621-32. DOI: 10.7326/0003-4819-153-10-201011160-00004
Sudeep HV, Venkatakrishna K, Amrutharaj B, Anitha, Shyamprasad K. A phytosterol-enriched saw palmetto supercritical CO2 extract ameliorates testosterone-induced benign prostatic hyperplasia by regulating the inflammatory and apoptotic proteins in a rat model. BMC Complement Altern Med. 2019 Oct 17;19(1):270. DOI: 10.1186/s12906-019-2697-z
Barry MJ, Meleth S, Lee JY, Kreder KJ, Avins AL, Nickel JC, et al. Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial. JAMA. 2011 Sep 28;306(12):1344-51. DOI: 10.1001/jama.2011.1364
Daukšas E, Venskutonis PR, Sivik B, Nillson T. Effect of fast CO2 pressure changes on the yield of lovage (Levisticum officinale Koch.) and celery (Apium graveolens L.) extracts. J Supercritical Fluids. 2002;22(3):201-10. DOI: 10.1016/s0896-8446(01)00115-2
Cu J-Q, Pu F, Shi Y, Perineau F, Delmas M, Gaset A. The chemical composition of lovage headspace and essential oils produced by solvent extraction with various solvents. J Essen Oil Res. 1990 Mar 1;2(2):53-9. DOI: 10.1080/10412905.1990.9697823
May P, Quirin K-W. Supercritical marigold flower CO2-extract - evergreen in evidence based cosmetic application. Cosmetic Science Technology. 2014;1:19-25.
Bakó E, Deli J, Tóth G. HPLC study on the carotenoid composition of Calendula products. J Biochem Biophys Methods. 2002 Oct 1;53(1-3):241-50. DOI: 10.1016/s0165-022x(02)00112-4
Della Loggia R, Tubaro A, Sosa S, Becker H, Saar S, Isaac O. The role of triterpenoids in the topical anti-inflammatory activity of Calendula officinalis flowers. Planta Med. 1994 Dec;60(6):516-20. DOI: 10.1055/s-2006-959562
Raal A, Orav A, Nesterovitsch J, Maidla K. Analysis of carotenoids, flavonoids and essential oil of Calendula officinalis cultivars growing in Estonia. Natural Product Commun. 2016 Aug 1;11(8):1157-1160. DOI: 10.1177/1934578x1601100831
Petrovic L, Lepojevic Z, Sovilj V, Adamovic D, Tesevic V. An investigation of CO2 extraction of marigold (Calendula officinalis L.). J Serbian Chem Soc. 2007 Jan 1;72(4):407-13. DOI: 10.2298/jsc0704407p
Hamburger M, Adler S, Baumann D, Förg A, Weinreich B. Preparative purification of the major anti-inflammatory triterpenoid esters from Marigold (Calendula officinalis). Fitoterapia. 2003 Jun 1;74(4):328-38. DOI: 10.1016/s0367-326x(03)00051-0
General Specification Marigold Flower CO2-to extract (organic). Available from: https://www.flavex.com/wp-content/uploads/2021/Spezi/EN_Spezi_Marigold_Flower_CO2-to_extract_organic_018_002.pdf
Kumar A, Kolay A, Havelikar U. Modern aspects of suppositories: A review. Eur J Pharmaceut Res. 2023 Aug 31;3(4):23-9. DOI: 10.24018/ejpharma.2023.3.4.68
Melnyk GM, Yarnykh TG, Herasymova IV. Experimental justification of the choice of suppository base for extemporaneous pessaries for childbirth preparation. Ukr J Milit Med. 2021 Jul 1;2(2):70-81. DOI: 10.46847/ujmm.2021.2(2)-070
Herasymova IV, Yurieva HB, Yarnykh TH, Voronenko DV. Research on the composition development of suppositories with echinacea and study of their stability. Ukr J Milit Med. 2022 Mar 31;3(1):67-74. DOI: 10.46847/ujmm.2022.1(3)-067
Takatori T, Shimono N, Higaki K, Kimura T. Evaluation of sustained release suppositories prepared with fatty base including solid fats with high melting points. Int J Pharm. 2004 Jul 1;278(2):275-82. DOI: 10.1016/j.ijpharm.2004.03.030
Mombekov S, Datkhayev U, Kalamkul D, Kozhamzharova A, Baidullayeva A, Assel M, et al. Study of the chemical components of CO2 extracts from the fruits of Sorbus aucuparia L. ScienceRise Pharmaceut Sci. 2024 Apr 30;(2 (48):83-9. DOI: 10.15587/2519-4852.2024.303000
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