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Formulation and validation of analytical methods for ursolic acid in Plantago major gel preparations

Yıl 2023, Cilt: 27 Sayı: 1, 290 - 298, 28.06.2025

Kartini Kartini Aminatush Sholichah Kurnia Wahyu Islamiyah Endang Wahyu Fitriani

Öz

Plantago major of the plantain family has been observed as a wound-healing plant species on account of its ursolic acid (UA) content. The study's objectives were twofold: to prepare UA gels from P. major and validate the analytical method using TLC-densitometer. Here, vacuum and open column chromatography were used to isolate UA from the methanol extract of P. major. Afterward, data on the compound’s physical properties and infrared (IR) spectroscopy, electrospray ionization mass spectrometry (ESI-MS), and Nuclear Magnetic Resonance (1H NMR, 13C NMR) results were analyzed. Carbomer and hydroxy propyl methyl cellulose (HPMC) were used as gelling agents to make the UA gel. To validate the analytical method, TLC-densitometer was performed using TLC silica gel 60 F254 plates (the stationary phase) and a mixture of toluene: ethyl acetate: formic acid (8:2:0.1, the developing solvent). The results showed that the UA gel was successfully prepared using both gelling agents and that its physical properties (i.e., visual forms, viscosity, and flow behavior) and pH values were maintained throughout the 90-day accelerated stability test (40±2°C; 75±5% RH). In addition, the method validation results indicated compliance with relevant parameters: linearity (r=0.998), limit of detection (4.55 ng/spot) and limit of quantification (15.17 ng/spot), recovery (95.04-116.82%), intraday precision (RSD=1.24–1.96%) and interday precision (RSD=6.29%). Overall, the UA gel is stable for 90 days (accelerated stability test), and the TLC-densitometry proposed in the research can be used to identify and measure the chemical content of a gel preparation.

Anahtar Kelimeler

Gel method validation Plantago major plantain stability test ursolic acid

Kaynakça

  • 1. Pironi AM, de Araújo PR, Fernandes MA, Salgado HRN, Chorilli M. Characteristics, biological properties and analytical methods of ursolic acid: A review. Critical Reviews in Analytical Chemistry. 2018;48(1):86-93. [CrossRef]
  • 2. Chiang LC, Chiang W, Chang MY, Lin CC. In vitro cytotoxic, antiviral and immunomodulatory effects of Plantago major and Plantago asiatica. American Journal of Chinese Medicine. 2003;31(2):225-34. [CrossRef]
  • 3. Kartini, Piyaviriyakul S, Siripong P, Vallisuta O. HPTLC simultaneous quantification of triterpene acids for quality control of Plantago major L. and evaluation of their cytotoxic and antioxidant activities. Industrial Crops and Products. 2014;60(0):239-46. [CrossRef]
  • 4. Ringbom T, Segura L, Noreen Y, Perera P, Bohlin L. Ursolic acid from Plantago major, a selective inhibitor of cyclooxygenase-2 catalyzed prostaglandin biosynthesis. Journal of Natural Products. 1998;61(10):1212-5. [CrossRef]
  • 5. Chiang LC, Ng LT, Chiang W, Chang MY, Lin CC. Immunomodulatory activities of flavonoids, monoterpenoids, triterpenoids, iridoid glycosides and phenolic compounds of Plantago species. Planta Med. 2003;69(7):600-4. [CrossRef]
  • 6. Stenholm A, Goransson U, Bohlin L. Bioassay-guided supercritical fluid extraction of cyclooxygenase-2 inhibiting substances in Plantago major L. Phytochemical Analysis. 2013;24(2):176-83. [CrossRef]
  • 7. Kolak U, Boǧa M, Uruşak EA, Ulubelen A. Constituents of Plantago major subsp. intermedia with antioxidant and anticholinesterase capacities. Turkish Journal of Chemistry. 2011;35(4):637-45. [CrossRef]
  • 8. López-Hortas L, Pérez-Larrán P, González-Muñoz MJ, Falqué E, Domínguez H. Recent developments on the extraction and application of ursolic acid. A review. Food Research International. 2018;103:130-49. [CrossRef]
  • 9. Lee T-H, Juang S-H, Hsu F-L, Wu C-Y. Triterpene Acids from the Leaves of Planchonella Duclitan (Blanco) Bakhuizan. Journal of the Chinese Chemical Society. 2005;52(6):1275-80. [CrossRef]
  • 10. Liu J. Pharmacology of oleanolic acid and ursolic acid. Journal of Ethnopharmacology. 1995;49(2):57-68. [CrossRef]
  • 11. Liu J. Oleanolic acid and ursolic acid: Research perspectives. Journal of Ethnopharmacology. 2005;100(1–2):92-4. [CrossRef]
  • 12. Pollier J, Goossens A. Oleanolic acid. Phytochemistry. 2012;77(0):10-5. [CrossRef]
  • 13. Shanmugam MK, Dai X, Kumar AP, Tan BK, Sethi G, Bishayee A. Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies. Biochem Pharmacol. 2013;85(11):1579-87. [CrossRef]
  • 14. Khwaza V, Oyedeji OO, Aderibigbe BA. Ursolic acid-based derivatives as potential anti-cancer agents: An update. International Journal of Molecular Sciences. 2020;21(16):5920. [CrossRef]
  • 15. Kartini, Piyaviriyakul S, Thongpraditchote S, Siripong P, Vallisuta O. Effects of Plantago major extracts and its chemical compounds on proliferation of cancer cells and cytokines production of lipopolysaccharide-activated THP-1 macrophages. Pharmacognosy Magazine. 2017;13(51):393-9. [CrossRef]
  • 16. Mukherjee H, Ojha D, Bharitkar YP, Ghosh S, Mondal S, Kaity S, et al. Evaluation of the wound healing activity of Shorea robusta, an Indian ethnomedicine, and its isolated constituent (s) in topical formulation. Journal of Ethnopharmacology. 2013;149(1):335-43. [CrossRef]
  • 17. Carletto B, Koga AY, Novatski A, Mainardes RM, Lipinski LC, Farago PV. Ursolic acid-loaded lipid-core nanocapsules reduce damage caused by estrogen deficiency in wound healing. Colloids and Surfaces B: Biointerfaces. 2021;203:111720. [CrossRef]
  • 18. Caligiani A, Malavasi G, Palla G, Marseglia A, Tognolini M, Bruni R. A simple GC–MS method for the screening of betulinic, corosolic, maslinic, oleanolic and ursolic acid contents in commercial botanicals used as food supplement ingredients. Food Chemistry. 2013;136(2):735-41. [CrossRef]
  • 19. Wójciak-Kosior M, Sowa I, Kocjan R, Nowak R. Effect of different extraction techniques on quantification of oleanolic and ursolic acid in Lamii albi flos. Industrial Crops and Products. 2013;44(0):373-7. [CrossRef]
  • 20. Gopal V, Mandal V, Mandal SC. HPTLC evaluation of oleanolic acid and ursolic acid from the methanol extract of Wattakaka volubilis. Journal of Acute Disease. 2014;3(1):59-61. [CrossRef]
  • 21. Patel MA, Vyas N. Development and validation of stability indicating HPTLC method for estimation of Ursolic acid. Asian Journal of Research in Chemistry. 2013;6(6):VI.
  • 22. Wojciak-Kosior M. Separation and determination of closely related triterpenic acids by high performance thin-layer chromatography after iodine derivatization. J Pharm Biomed Anal. 2007;45(2):337-40. [CrossRef]
  • 23. Chaouche TM, Haddouchi F, Ksouri R, Atik-Bekkara F. Evaluation of antioxidant activity of hydromethanolic extracts of some medicinal species from South Algeria. Journal of the Chinese Medical Association. 2014;77(6):302-7. [CrossRef]
  • 24. Seebacher W, Simic N, Weis R, Saf R, Kunert O. Complete assignments of 1H and 13C NMR resonances of oleanolic acid, 18α-oleanolic acid, ursolic acid and their 11-oxo derivatives. Magnetic Resonance in Chemistry. 2003;41(8):636-8. [CrossRef]
  • 25. Silva MG, Vieira IG, Mendes FN, Albuquerque IL, dos Santos RN, Silva FO, et al. Variation of ursolic acid content in eight Ocimum species from northeastern Brazil. Molecules. 2008;13(10):2482-7. [CrossRef]
  • 26. Rowe RC, Sheskey PJ, Owen SC. Handbook of pharmaceutical excipients: Pharmaceutical press London; 2006. 27. Dhawan S, Medhi B, Chopra S. Formulation and evaluation of diltiazem hydrochloride gels for the treatment of anal fissures. Scientia Pharmaceutica. 2009;77(2):465-82. [CrossRef]
  • 28. Singh Y. Martin’s physical pharmacy and pharmaceutical sciences: Department of Pharmaceutics Ernest Mario School of Pharmacy Rutgers, The State University of New Jersey; 2006.
  • 29. Barel AO, Paye M, Maibach HI. Handbook of cosmetic science and technology: CRC press; 2014.
  • 30. Jamal M, Amir M, Ali Z, Mujeeb M. A comparative study for the extraction methods and solvent selection for isolation, quantitative estimation and validation of ursolic acid in the leaves of Lantana camara by HPTLC method. Future Journal of Pharmaceutical Sciences. 2018;4(2):229-33. [CrossRef]
  • 31. Riyanto R. Validasi & Verifikasi Metode Uji DEEPUBLISH. Sleman: Deepublish; 2014.
  • 32. Sudjono TA. Pengaruh Konsentrasi Gelling Agent Carbomer 934 dan HPMC Pada Formulasi Gel Lendir Bekicot (Achatina fulica) Terhadap Kecepatan Penyembuhan Luka Bakar Pada Punggung Kelinci. PHARMACON: Jurnal Farmasi Indonesia. 2012;13(1):6-11.

Yıl 2023, Cilt: 27 Sayı: 1, 290 - 298, 28.06.2025

Kartini Kartini Aminatush Sholichah Kurnia Wahyu Islamiyah Endang Wahyu Fitriani

Öz

Kaynakça

  • 1. Pironi AM, de Araújo PR, Fernandes MA, Salgado HRN, Chorilli M. Characteristics, biological properties and analytical methods of ursolic acid: A review. Critical Reviews in Analytical Chemistry. 2018;48(1):86-93. [CrossRef]
  • 2. Chiang LC, Chiang W, Chang MY, Lin CC. In vitro cytotoxic, antiviral and immunomodulatory effects of Plantago major and Plantago asiatica. American Journal of Chinese Medicine. 2003;31(2):225-34. [CrossRef]
  • 3. Kartini, Piyaviriyakul S, Siripong P, Vallisuta O. HPTLC simultaneous quantification of triterpene acids for quality control of Plantago major L. and evaluation of their cytotoxic and antioxidant activities. Industrial Crops and Products. 2014;60(0):239-46. [CrossRef]
  • 4. Ringbom T, Segura L, Noreen Y, Perera P, Bohlin L. Ursolic acid from Plantago major, a selective inhibitor of cyclooxygenase-2 catalyzed prostaglandin biosynthesis. Journal of Natural Products. 1998;61(10):1212-5. [CrossRef]
  • 5. Chiang LC, Ng LT, Chiang W, Chang MY, Lin CC. Immunomodulatory activities of flavonoids, monoterpenoids, triterpenoids, iridoid glycosides and phenolic compounds of Plantago species. Planta Med. 2003;69(7):600-4. [CrossRef]
  • 6. Stenholm A, Goransson U, Bohlin L. Bioassay-guided supercritical fluid extraction of cyclooxygenase-2 inhibiting substances in Plantago major L. Phytochemical Analysis. 2013;24(2):176-83. [CrossRef]
  • 7. Kolak U, Boǧa M, Uruşak EA, Ulubelen A. Constituents of Plantago major subsp. intermedia with antioxidant and anticholinesterase capacities. Turkish Journal of Chemistry. 2011;35(4):637-45. [CrossRef]
  • 8. López-Hortas L, Pérez-Larrán P, González-Muñoz MJ, Falqué E, Domínguez H. Recent developments on the extraction and application of ursolic acid. A review. Food Research International. 2018;103:130-49. [CrossRef]
  • 9. Lee T-H, Juang S-H, Hsu F-L, Wu C-Y. Triterpene Acids from the Leaves of Planchonella Duclitan (Blanco) Bakhuizan. Journal of the Chinese Chemical Society. 2005;52(6):1275-80. [CrossRef]
  • 10. Liu J. Pharmacology of oleanolic acid and ursolic acid. Journal of Ethnopharmacology. 1995;49(2):57-68. [CrossRef]
  • 11. Liu J. Oleanolic acid and ursolic acid: Research perspectives. Journal of Ethnopharmacology. 2005;100(1–2):92-4. [CrossRef]
  • 12. Pollier J, Goossens A. Oleanolic acid. Phytochemistry. 2012;77(0):10-5. [CrossRef]
  • 13. Shanmugam MK, Dai X, Kumar AP, Tan BK, Sethi G, Bishayee A. Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies. Biochem Pharmacol. 2013;85(11):1579-87. [CrossRef]
  • 14. Khwaza V, Oyedeji OO, Aderibigbe BA. Ursolic acid-based derivatives as potential anti-cancer agents: An update. International Journal of Molecular Sciences. 2020;21(16):5920. [CrossRef]
  • 15. Kartini, Piyaviriyakul S, Thongpraditchote S, Siripong P, Vallisuta O. Effects of Plantago major extracts and its chemical compounds on proliferation of cancer cells and cytokines production of lipopolysaccharide-activated THP-1 macrophages. Pharmacognosy Magazine. 2017;13(51):393-9. [CrossRef]
  • 16. Mukherjee H, Ojha D, Bharitkar YP, Ghosh S, Mondal S, Kaity S, et al. Evaluation of the wound healing activity of Shorea robusta, an Indian ethnomedicine, and its isolated constituent (s) in topical formulation. Journal of Ethnopharmacology. 2013;149(1):335-43. [CrossRef]
  • 17. Carletto B, Koga AY, Novatski A, Mainardes RM, Lipinski LC, Farago PV. Ursolic acid-loaded lipid-core nanocapsules reduce damage caused by estrogen deficiency in wound healing. Colloids and Surfaces B: Biointerfaces. 2021;203:111720. [CrossRef]
  • 18. Caligiani A, Malavasi G, Palla G, Marseglia A, Tognolini M, Bruni R. A simple GC–MS method for the screening of betulinic, corosolic, maslinic, oleanolic and ursolic acid contents in commercial botanicals used as food supplement ingredients. Food Chemistry. 2013;136(2):735-41. [CrossRef]
  • 19. Wójciak-Kosior M, Sowa I, Kocjan R, Nowak R. Effect of different extraction techniques on quantification of oleanolic and ursolic acid in Lamii albi flos. Industrial Crops and Products. 2013;44(0):373-7. [CrossRef]
  • 20. Gopal V, Mandal V, Mandal SC. HPTLC evaluation of oleanolic acid and ursolic acid from the methanol extract of Wattakaka volubilis. Journal of Acute Disease. 2014;3(1):59-61. [CrossRef]
  • 21. Patel MA, Vyas N. Development and validation of stability indicating HPTLC method for estimation of Ursolic acid. Asian Journal of Research in Chemistry. 2013;6(6):VI.
  • 22. Wojciak-Kosior M. Separation and determination of closely related triterpenic acids by high performance thin-layer chromatography after iodine derivatization. J Pharm Biomed Anal. 2007;45(2):337-40. [CrossRef]
  • 23. Chaouche TM, Haddouchi F, Ksouri R, Atik-Bekkara F. Evaluation of antioxidant activity of hydromethanolic extracts of some medicinal species from South Algeria. Journal of the Chinese Medical Association. 2014;77(6):302-7. [CrossRef]
  • 24. Seebacher W, Simic N, Weis R, Saf R, Kunert O. Complete assignments of 1H and 13C NMR resonances of oleanolic acid, 18α-oleanolic acid, ursolic acid and their 11-oxo derivatives. Magnetic Resonance in Chemistry. 2003;41(8):636-8. [CrossRef]
  • 25. Silva MG, Vieira IG, Mendes FN, Albuquerque IL, dos Santos RN, Silva FO, et al. Variation of ursolic acid content in eight Ocimum species from northeastern Brazil. Molecules. 2008;13(10):2482-7. [CrossRef]
  • 26. Rowe RC, Sheskey PJ, Owen SC. Handbook of pharmaceutical excipients: Pharmaceutical press London; 2006. 27. Dhawan S, Medhi B, Chopra S. Formulation and evaluation of diltiazem hydrochloride gels for the treatment of anal fissures. Scientia Pharmaceutica. 2009;77(2):465-82. [CrossRef]
  • 28. Singh Y. Martin’s physical pharmacy and pharmaceutical sciences: Department of Pharmaceutics Ernest Mario School of Pharmacy Rutgers, The State University of New Jersey; 2006.
  • 29. Barel AO, Paye M, Maibach HI. Handbook of cosmetic science and technology: CRC press; 2014.
  • 30. Jamal M, Amir M, Ali Z, Mujeeb M. A comparative study for the extraction methods and solvent selection for isolation, quantitative estimation and validation of ursolic acid in the leaves of Lantana camara by HPTLC method. Future Journal of Pharmaceutical Sciences. 2018;4(2):229-33. [CrossRef]
  • 31. Riyanto R. Validasi & Verifikasi Metode Uji DEEPUBLISH. Sleman: Deepublish; 2014.
  • 32. Sudjono TA. Pengaruh Konsentrasi Gelling Agent Carbomer 934 dan HPMC Pada Formulasi Gel Lendir Bekicot (Achatina fulica) Terhadap Kecepatan Penyembuhan Luka Bakar Pada Punggung Kelinci. PHARMACON: Jurnal Farmasi Indonesia. 2012;13(1):6-11.
Toplam 31 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Farmakognozi
Bölüm Articles
Yazarlar

Kartini Kartini 0000-0002-7685-9933

Aminatush Sholichah 0009-0009-2170-4369

Kurnia Wahyu Islamiyah 0000-0003-2360-2576

Endang Wahyu Fitriani 0000-0002-3441-3570

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 1

Kaynak Göster

APA Kartini, K., Sholichah, A., Islamiyah, K. W., Fitriani, E. W. (2025). Formulation and validation of analytical methods for ursolic acid in Plantago major gel preparations. Journal of Research in Pharmacy, 27(1), 290-298.
AMA Kartini K, Sholichah A, Islamiyah KW, Fitriani EW. Formulation and validation of analytical methods for ursolic acid in Plantago major gel preparations. J. Res. Pharm. Haziran 2025;27(1):290-298.
Chicago Kartini, Kartini, Aminatush Sholichah, Kurnia Wahyu Islamiyah, ve Endang Wahyu Fitriani. “Formulation and Validation of Analytical Methods for Ursolic Acid in Plantago Major Gel Preparations”. Journal of Research in Pharmacy 27, sy. 1 (Haziran 2025): 290-98.
EndNote Kartini K, Sholichah A, Islamiyah KW, Fitriani EW (01 Haziran 2025) Formulation and validation of analytical methods for ursolic acid in Plantago major gel preparations. Journal of Research in Pharmacy 27 1 290–298.
IEEE K. Kartini, A. Sholichah, K. W. Islamiyah, ve E. W. Fitriani, “Formulation and validation of analytical methods for ursolic acid in Plantago major gel preparations”, J. Res. Pharm., c. 27, sy. 1, ss. 290–298, 2025.
ISNAD Kartini, Kartini vd. “Formulation and Validation of Analytical Methods for Ursolic Acid in Plantago Major Gel Preparations”. Journal of Research in Pharmacy 27/1 (Haziran 2025), 290-298.
JAMA Kartini K, Sholichah A, Islamiyah KW, Fitriani EW. Formulation and validation of analytical methods for ursolic acid in Plantago major gel preparations. J. Res. Pharm. 2025;27:290–298.
MLA Kartini, Kartini vd. “Formulation and Validation of Analytical Methods for Ursolic Acid in Plantago Major Gel Preparations”. Journal of Research in Pharmacy, c. 27, sy. 1, 2025, ss. 290-8.
Vancouver Kartini K, Sholichah A, Islamiyah KW, Fitriani EW. Formulation and validation of analytical methods for ursolic acid in Plantago major gel preparations. J. Res. Pharm. 2025;27(1):290-8.