PVP solid dispersions containing Poloxamer 407 or TPGS for the improvement of ursolic acid release
DOI:
https://doi.org/10.1590/s2175-97902023e21217Keywords:
Ursolic acid, Solid dispersions, Solvent method, Water-solubilityAbstract
Solid dispersions (SDs) of ursolic acid (UA) were developed using polyvinylpyrrolidone K30 (PVP K30) in combination with non-ionic surfactants, such as D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) or poloxamer 407 (P407) with the aim of enhancing solubility and in vitro release of the UA. SDs were investigated using a 24 full factorial design, subsequently the selected formulations were characterized for water solubility, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), particle diameter, scanning electron microscopy, drug content, physical-chemical stability and in vitro release profile. SDs showed higher UA water-solubility than physical mixtures (PMs), which was attributed by transition of the drug from crystalline to amorphous or molecular state in the SDs, as indicated by XRD and DSC analyses. SD1 (with P407) and SD2 (with TPGS) were chosen for further investigation because they had higher drug load. SD1 proved to be more stable than SD2, revealing that P407 contributed to ensure the stability of the UA. Furthermore, SD1 and SD2 increased UA release by diffusion and swelling-controlled transport, following the Weibull model. Thus, solid dispersions obtained with PVP k-30 and P407 proved to be advantageous to enhance aqueous solubility and stability of UA.
Downloads
References
Baghel S, Cathcart H, O’Reilly NJ. Polymeric amorphous solid dispersions: A review of amorphization, crystallization, stabilization, solid-state characterization, and aqueous solubilization of biopharmaceutical Classification System Class II Drugs. J Pharm Sci. 2016;105(9):2527-2544.
Chakraborty M, Bhattacharjee A, Kamath JV. Cardioprotective effect of ursolic acid against doxorubicin induced cardiotoxicity. Indian Drugs. 2016;51(11):65-71.
Chan SY, Chung YY, Cheah XZ, Tan EYL, Quah J. The characterization and dissolution performances of spray dried solid dispersion of ketoprofen in hydrophilic carriers. Asian J Pharm Sci . 2015;10(5):372-385.
Chaudhari SP, Dugar RP. Application of surfactants in solid dispersion technology for improving solubility of poorly water soluble drugs. J Drug Deliv Sci Technol. 2017;41(1):68-77.
Chokshi RJ, Zia H, Sandhu HK, Shah NH, Malick A, Chokshi RJ, et al. Improving the dissolution rate of poorly water soluble drug by solid dispersion and solid solution: pros and cons. Drug Deliv. 2007;14(1):33-45.
Colombo P, Bettini R, Massimo G, Catellani PL, Santi P, Peppas NA. Drug diffusion front movement is important in drug release control from swellable matrix tablets. J Pharm Sci . 1995;84(8):991-997.
Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci . 2001;13(2):123-133.
El-Badry M, Fetih G, Fathy M. Improvement of solubility and dissolution rate of indomethacin by solid dispersions in Gelucire 50/13 and PEG4000. Saudi Pharm Soc. 2009;17(3):217-225.
Eloy JO, Oliveira ECV, Marotta-Oliveira SS, Saraiva J, Marchetti JM. Desenvolvimento e validação de um método analítico por CLAE para quantificação de ácido ursólico em dispersões sólidas. Quim Nova. 2012;35(5):1036-1040.
Eloy JO, Marchetti JM. Solid dispersions containing ursolic acid in Poloxamer 407 and PEG 6000 : A comparative study of fusion and solvent methods. Powder Technol. 2014;253(1):98-106.
Eloy JO, Saraiva J, De Albuquerque S, Marchetti JM. Preparation, characterization and evaluation of the in vivo trypanocidal activity of ursolic acid-loaded solid dispersion with poloxamer 407 and sodium caprate. Braz J Pharm Sci . 2015;51(1):101-109.
Feng D, Peng T, Huang Z, Singh V, Shi Y, Wen T, et al. Polymer - Surfactant System Based Amorphous Solid Dispersion : Precipitation Inhibition and Bioavailability Enhancement of Itraconazole. Pharmaceutics. 2018;10(2):1-15.
Feng XM, Su XL. Anticancer effect of ursolic acid via mitochondria-dependent pathways (Review). Oncol Lett. 2019;17(6):4761-4767.
Goddeeris C, Van den Mooter G. Free flowing solid dispersions of the anti-HIV drug UC 781 with Poloxamer 407 and a maximum amount of TPGS 1000: Investigating the relationship between physicochemical characteristics and dissolution behaviour. Eur J Pharm Sci . 2008;35(1-2):104-113.
Gudoityte E, Arandarcikaite O, Mazeikiene I, Bendokas V, Liobikas J. Ursolic and oleanolic acids: Plant metabolites with neuroprotective potential. International Journal of Molecular Sciences. 2021;22(9):1-15.
Guo Y, Shalaev E, Smith S. Physical stability of pharmaceutical formulations: Solid-state characterization of amorphous dispersions. Trends Anal Chem. 2013;49(1):137-144.
Guzmán-Ávila R, Flores-Morales V, Paoli P, Camici G, Ramírez-Espinosa JJ, Cerón-Romero L, et al. Ursolic acid derivatives as potential antidiabetic agents: In vitro, in vivo, and in silico studies. Drug Dev Res. 2018;79(2):70-80.
Karolewicz B, Gajda M, Górniak A, Owczarek A, Mucha I. Pluronic F127 as a suitable carrier for preparing the imatinib base solid dispersions and its potential in development of a modified release dosage forms. 2017;130(1):383-390.
Kolašinac N, Kachrimanis K, Homšek I, Grujić B, Urić Z, Ibrić S. Solubility enhancement of desloratadine by solid dispersion in poloxamers. Int J Pharm. 2012;436(1-2):161-170.
Lang B, Liu S, McGinity JW, Williams RO. Effect of hydrophilic additives on the dissolution and pharmacokinetic properties of itraconazole-enteric polymer hot-melt extruded amorphous solid dispersions. Drug Dev Ind Pharm. 2016;42(3):429-445.
Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000;50(1):47-60.
Mendes LC, Rodrigues RC, Silva EP. Thermal, structural and morphological assessment of PVP/HA composites. J Therm Anal Calorim. 2010;101(3):899-905.
Nair AR, Lakshman YD, Anand VSK, Sree KSN, Bhat K, Dengale SJ. Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology. AAPS Pharm Sci Tech. 2020; 21(8):309-329.
Nascimento P, Lemos T, Bizerra A, Arriaga Â, Ferreira D, Santiago G, et al. Antibacterial and Antioxidant Activities of Ursolic Acid and Derivatives. Molecules. 2014;19(1):1317-1327.
Newa M, Bhandari KH, Li DX, Kwon TH, Kim JA, Yoo BK, Woo JS, Lyoo WS, Yong CS, Choi HG. Preparation, characterization and in vivo evaluation of ibuprofen binary solid dispersions with poloxamer 188. Int J Pharm . 2007;343(1-2):228-237.
Panizzon GP, Bueno FG, Ueda-Nakamura T, Nakamura CV, Dias Filho BP. Manufacturing different types of solid dispersions of BCS class iv polyphenol (daidzein) by spray drying: Formulation and bioavailability. Pharmaceutics . 2019;11(10):1-17.
Papadopoulou V, Kosmidis K, Vlachou M, Macheras P. On the use of the Weibull function for the discernment of drug release mechanisms. Int J Pharm . 2006;309(1-2):44-50.
Patel RP, Patel MM. Physicochemical characterization and dissolution study of solid dispersions of lovastatin with polyethylene glycol 4000 and polyvinylpyrrolidone K30. Pharm Dev Technol. 2007;12(1):21-33.
Petrilli R, Fonseca R, Lopez V. Physical methods for topical skin drug delivery : concepts and applications. Braz J Pharm Sci . 2016;54(1)1-19.
Salau VF, Erukainure OL, Ayeni G, Ibeji CU, Islam MS. Modulatory effect of ursolic acid on neurodegenerative activities in oxidative brain injury: An ex vivo study. J Food Biochem. 2021;45(2):13597-13607.
Sethia S, Squillante E. Solid dispersion of carbamazepine in PVP K30 by conventional solvent evaporation and supercritical methods. Int J Pharm . 2004;272(1-2):1-10.
Simonazzi A, Davies C, Cid AG, Gonzo E, Parada L, Bermúdez JM. Preparation and Characterization of Poloxamer 407 Solid Dispersions as an Alternative Strategy to Improve Benznidazole Bioperformance. J Pharm Sci . 2018;107(11):2829-2836.
Song IS, Cha JS, Choi MK. Characterization, in vivo and in vitro evaluation of solid dispersion of curcumin containing D-α-Tocopheryl polyethylene glycol 1000 succinate and mannitol. Molecules. 2016;21(10):1386-1402.
Szafraniec J, Antosik A, Knapik-Kowalczuk J, Chmiel K, Kurek M, Gawlak K, et al. The self-assembly phenomenon of poloxamers and its effect on the dissolution of a poorly soluble drug from solid dispersions obtained by solvent methods. Pharmaceutics . 2019;11(3):130-152.
Tambosi G, Coelho PF, Soares L, Lenschow ICS, Zétola M, Stulzer HK, et al. Challenges to improve the biopharmaceutical properties of poorly water-soluble drugs and the application of the solid dispersion technology. Rev Mater. 2018; 23(4):12224-12240.
Tran P, Pyo Y, Kim D, Lee S, Kim J, Park J. Overview of the Manufacturing Methods of Solid Dispersion Technology for Improving the Solubility of Poorly Water-Soluble Drugs and Application to Anticancer Drugs. Pharmaceutics . 2019; 11(3):132-158.
US EPA, Estimation Program Interface (EPI) Suite. Ver. 4.0. Jan, 2009. http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm apud PubChem. Open Chemistry Database. https://pubchem.ncbi.nlm.nih.gov/compound/Ursolic_acid#section=Top
» http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
» https://pubchem.ncbi.nlm.nih.gov/compound/Ursolic_acid#section=Top
Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today. 2007;12(23-24):1068-1075.
Vo CLN, Park C, Lee BJ. Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J Pharm Biopharm . 2013;85(3):799-813.
Vyas V, Sancheti P, Karekar P, Shah M, Pore Y. Physicochemical characterization of solid dispersion systems of tadalafil with poloxamer 407. Acta Pharm. 2009;59(4):453-461.
Wang C, Gao Y, Zhang Z, Chen C, Chi Q, Xu K, et al. Ursolic acid protects chondrocytes, exhibits anti-inflammatory properties via regulation of the NF-κB/NLRP3 inflammasome pathway and ameliorates osteoarthritis. Biomed Pharmacother. 2020;130(1):110568-110577.
Yoon I, Cho H. Soluplus ®/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan. Drug Des Dev Ther. 2015;22(9):2745-2756.
Yuana T, Qin L, Wang Z, Nie J, Guo Z, Li G, et al. Solid lipid dispersion of calcitriol with enhanced dissolution and stability. Asian J Pharm Sci . 2013;8(1):39-47.
Zhang Y, Xue K, Zhao E, Li Y, Yao L, Yang X, et al. Determination of oleanolic acid and ursolic acid in Chinese medicinal plants using HPLC with PAH polymeric C18. Pharmacogn Mag. 2013;9(1):19-24.
Zhou Z, Tong HHY, Li L, Shek FLY, Lv Y, Zheng Y. Synthesis, characterization and thermal analysis of ursolic acid solid forms. Cryst Res Technol. 2015;50(7):538-548.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on line journal has open and free access.
