Preparation and evaluation of valsartan orodispersible tablets using PVP-K30 and HPMC E3 solid dispersions by the solvent evaporation method

Mahsa Zaghian , Alireza Homayouni , Zahra Keshavarz, Ladan Dayani, Zeinab Fakhari, Fatemeh Sadat Osooli

Abstract


Background and purpose: Valsartan (Val), administered for hypertension, exhibits poor water solubility, resulting in low oral bioavailability. This study aimed to enhance the dissolution of Val by preparing orodispersible tablets (ODT) using solid dispersion (SD) technology with PVP and HPMC as hydrophilic carriers.

Experimental approach: After preparation of the SDs and physical mixtures of Val: PVP and Val: HPMC at various ratios, the physicochemical characteristics of these mixtures were analyzed. Then, the ODTs were prepared using the best SD sample and evaluated through USP tests.

Findings/Results: The saturation solubility of Val: PVP 1:1 and 1:2 at pH 6.8 was notably higher than that of pure Val. The SDs exhibited a superior dissolution rate compared to pure Val and its physical mixtures. Increasing the drug/carrier ratio resulted in a decrease in the percentage of drug in SD, with Val: PVP 1:1 SD showing significantly higher drug loading percentage compared to other formulations. All formulations exhibited entrapment efficiencies above 80%. Also, the flow of the SDs was good based on the Hausner ratio.

Conclusion and implications: The SDs exhibited more favorable attributes compared to pure Val and its physical mixtures. The research suggests that PVP and HPMC are effective carriers for improving the solubility and dissolution rate of Val. Additionally, mannitol was identified as a beneficial excipient for achieving the desired properties of ODTs. The findings can be applied to other drugs with similar solubility issues, paving the way to improve therapeutic outcomes for patients.

 


Keywords


HPMC; PVP; Solid dispersion; Valsartan.

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References


Yan YD, Sung JH, Kim KK, Kim DW, Kim JO, Lee BJ, et al. Novel valsartan-loaded solid dispersion with enhanced bioavailability and no crystalline changes. Int J Pharm. 2012;422(1-2):202-210. DOI: 10.1016/j.ijpharm.2011.10.053.

Wells T, Blumer J, Meyers KEC, Neto JPR, Meneses R, Litwin M, et al. Effectiveness and safety of valsartan in children aged 6 to 16 years with hypertension. J Clin Hypertens (Greenwich). 2011;13(5):357-365. DOI: 10.1111/j.1751-7176.2011.00432.x.

van der Merwe J, Steenekamp J, Steyn D, Hamman J. The role of functional excipients in solid oral dosage forms to overcome poor drug dissolution and bioavailability. Pharmaceutics. 2020;12(5):393,1-17. DOI: 10.3390/pharmaceutics12050393.

Xu WJ, Xie HJ, Cao QR, Shi LL, Cao Y, Zhu XY, et al. Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers. Drug Deliv. 2016;23(1):41-48. DOI: 10.3109/10717544.2014.903012.

Zaini E, Umar S, Firdaus N. Improvement of dissolution rate of valsartan by solid dispersion system using D(−) mannitol. Asian J Pharm Clin Res. 2017;10:288-290. DOI: 10.22159/ajpcr.2017.v10i3.16171.

Medarević D, Cvijić S, Dobričić V, Mitrić M, Djuriš J, Ibrić S. Assessing the potential of solid dispersions to improve dissolution rate and bioavailability of valsartan: in vitro-in silico approach. Eur J Pharm Sci. 2018;124:188-198. DOI: 10.1016/j.ejps.2018.08.026.

Jensen CE de M, dos Santos RAS, Denadai AML, Santos CFF, Braga ANG, Sinisterra RD. Pharmaceutical composition of valsartan: beta-cyclodextrin: physico-chemical characterization and anti-hypertensive evaluation. Molecules. 2010;15(6):4067-4084. DOI: 10.3390/molecules15064067.

Rangel-Yagui CO, Pessoa Jr A, Tavares LC. Micellar solubilization of drugs. J Pharm Pharm Sci. 2005;8(2):147-165. PMID: 16124926.

Sharma A, Jain CP. Preparation and characterization of solid dispersions of carvedilol with PVP K30. Res Pharm Sci. 2010;5(1):49-56. PMID: 21589768.

Alves LDS, de La Roca Soares MF, de Albuquerque CT, da Silva ÉR, Vieira ACC, Fontes DAF, et al. Solid dispersion of efavirenz in PVP K-30 by conventional solvent and kneading methods. Carbohydr Polym. 2014;104:166-174. DOI: 10.1016/j.carbpol.2014.01.027.

Kakran M, Sahoo NG, Li L. Dissolution enhancement of quercetin through nanofabrication, complexation, and solid dispersion. Colloids Surf B Biointerfaces. 2011;88(1):121-130. DOI: 10.1016/j.colsurfb.2011.06.020.

Kyaw Oo M, Mandal UK, Chatterjee B. Polymeric behavior evaluation of PVP K30-poloxamer binary carrier for solid dispersed nisoldipine by experimental design. Pharm Dev Technol. 2017;22(1):2-12. DOI: 10.3109/10837450.2015.1116568.

Sapkal SB, Shinde SA, Darakhe RA, Shikhande VN. Solid dispersion of valsartan for solubility improvement using β-cyclodextrin. MOJ Bioequiv Availab. 2018;5(6):313-319. DOI: 10.15406/mojbb.2018.05.00121.

Desai P, Deshmukh N, Rajguru A, Khedkar R, Jadhav R. Formulation and evaluation of valsartan solid dispersion for improvement of dissolution profile. WJBPHS. 2023;15(2):208-224. DOI: 10.30574/wjbphs.2023.15.2.0314.

Shirsath RN, Goswami KA. Design and development of solid dispersion of valsartan by a lyophilization technique: A 32 factorial design approach. Micro Nanosyst. 2021;13(1):90-102. DOI: 10.2174/1876402912666200206155430.

Mahapatra AK, Pn M, Biswal S, Mahapatra A, Pradhan S. Dissolution enhancement and physicochemical characterization of valsartan in solid dispersions with β-CD, HP β-CD, and PVP K-30. Dissolution Technol. 2011;18:39-45. DOI: 10.14227/DT180111P39.

Shen YC, Lee MY, Lin CCH, Chen CH. Orally disintegrating olanzapine for the treatment of a manic patient with esophageal stricture plus chronic pharyngitis. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(2):541-542. DOI: 10.1016/j.pnpbp.2006.09.003.

Alburyhi M, Saif A, Abduh Y, Mohamed S, Hamidaddin M. Formulation and evaluation of lisinopril orally disintegrating tablets. World J Pharm Pharm Sci. 2023;12(9):357-369. DOI: 10.20959/wjpps20239-25742.

Motallae S, Taheri A, Homayouni A. Preparation and characterization of solid dispersions of celecoxib obtained by spray-drying ethanolic suspensions containing PVP-K30 or isomalt. J Drug Deliv Sci Tech. 2018;46:188-196. DOI: 10.1016/j.jddst.2018.05.020.

Sapkal S, Shinde S. Solid dispersion of valsartan for solubility improvement using β-cyclodextrin. MOJ Bioequivalence Bioavailab. 2018;5(6):313-319. DOI: 10.15406/mojbb.2018.05.00121.

Homayouni A, Sadeghi F, Nokhodchi A, Varshosaz J, Garekani HA. Preparation and characterization of celecoxib solid dispersions; comparison of poloxamer-188 and PVP-K30 as carriers. Iran J Basic Med Sci. 2014;17(5):322-331. DOI: 10.22038/ijbms.2014.2781.

Basavaiah K, Nagegowda P, Ramakrishna V. Determination of drug content of pharmaceuticals containing ranitidine by titrimetry and spectrophotometry in non-aqueous medium. Sci Asia. 2005;31:207-214. DOI: 10.2306/scienceasia1513-1874.2005.31.207.

Homayouni A, Sohrabi M, Amini M, Varshosaz J, Nokhodchi A. Effect of high pressure homogenization on physicochemical properties of curcumin nanoparticles prepared by antisolvent crystallization using HPMC or PVP. Mater Sci Eng C Mater Biol Appl. 2019;98:185-196. DOI: 10.1016/j.msec.2018.12.128.

Diane MG, Twinbrook Parkway, Rockville MD. In: United States Pharmacopeia and National Formulary (USP 42-NF 37). United States Pharmacopeial Convention. 2019: 6778-6781.

Baird JA, Taylor LS. Evaluation of amorphous solid dispersion properties using thermal analysis techniques. Adv Drug Deliv Rev. 2012;64(5):396-421. DOI: 10.1016/j.addr.2011.07.009.

Chaulang G, Patil K, Ghodke D, Khan S, Yeole P. Preparation and characterization of solid dispersion tablet of furosemide with crospovidone. RJPT. 2008;1(4):386-389. DOI: 10.5958/0974-360X.

Diane MG, Twinbrook P, Rockville MD. United States Pharmacopeial Convention. In: United States Pharmacopeia and National Formulary (USP 42-NF 37).: United States Pharmacopeial Convention; 2019: 7079-70782.

Zaini E, Wahyuni YS, Halim A, Yuliandra Y. Preparation of eutectic mixture of ketoprofen and nicotinamide for enhanced dissolution rate. Int J Pharm Sci Rev Res. 2015;35(1):161-164.

Yadav PS, Kumar V, Singh UP, Bhat HR, Mazumder B. Physicochemical characterization and in vitro dissolution studies of solid dispersions of ketoprofen with PVP K30 and d-mannitol. Saudi Pharm J. 2013;21(1):77-84. DOI: 10.1016/j.jsps.2011.12.007.

Tita IC, Tita B, Toma CC, Marian E, Vicas L. Thermal behavoiur of valsartan active substance and in pharmaceutical products. Rev Chim. 2017;68(10):2307-2310. DOI: 10.37358/RC.17.10.5874.

Azeez Betti N. Thermogravimetric analysis on PVA/PVP blend under air atmosphere. Eng and Tech Journal. 2016;34(13A):2433-2442.

Available at https://doi.org/10.30684/etj.34.13A.6.

Tran P, Pyo YC, Kim DH, Lee SE, Kim JK, Park JS. 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):132,1-26. DOI: 10.3390/pharmaceutics11030132.

Lafountaine JS, Prasad LK, Brough C, Miller DA, McGinity JW, Williams RO. Thermal processing of PVP- and HPMC-based amorphous solid dispersions. AAPS PharmSciTech. 2015;17(1):120-132. DOI: 10.1208/s12249-015-0417-7.

Fitriani L, Haqi A, Zaini E. Preparation and characterization of solid dispersion freeze-dried efavirenz-polyvinylpyrrolidone K-30. J Adv Pharm Technol Res. 2016;7:105-109. DOI: 10.4103/2231-4040.184592.

Slámová M, Školáková T, Školáková A, Patera J, Zámostný P. Preparation of solid dispersions with respect to the dissolution rate of active substance. J Drug Deliv Sci Technol. 2020;56:101518,1-27. DOI: 10.1016/j.jddst.2020.101518.

Patil PH, Belgamwar VS, Patil PR, Surana SJ. Solubility enhancement of raloxifene using inclusion complexes and cogrinding method. J Pharm. 2013;2013:527380,1-10. DOI: 10.1155/2013/527380.

Sethia S, Squillante E. Solid dispersion of carbamazepine in PVP K30 by conventional solvent evaporation and supercritical methods. Int J Pharm. 2004;272(1):1-10. DOI: 10.1016/j.ijpharm.2003.11.025.

Oo MK, Mandal UK, Chatterjee B. Polymeric behavior evaluation of PVP K30-poloxamer binary carrier for solid dispersed nisoldipine by experimental design. Pharm Dev Technol. 2015;22(1):2-12. DOI: 10.3109/10837450.2015.1116568.

Tran TTD, Tran PHL, Lee BJ. Dissolution-modulating mechanism of alkalizers and polymers in a nanoemulsifying solid dispersion containing ionizable and poorly water-soluble drug. Eur J Pharm Biopharm. 2009;72(1):83-90. DOI: 10.1016/j.ejpb.2008.12.009.

Uchiyama H, Tozuka Y, Imono M, Takeuchi H. Transglycosylated stevia and hesperidin as pharmaceutical excipients: Dramatic improvement in drug dissolution and bioavailability. Eur J Pharm Biopharm. 2010;76(2):238-244. DOI: 10.1016/j.ejpb.2010.07.006.

Ren F, Jing Q, Tang Y, Shen Y, Chen J, Gao F, et al. Characteristics of bicalutamide solid dispersions and improvement of the dissolution. Drug Dev Ind Pharm. 2006;32(8):967-972. DOI: 10.1080/03639040600637606.

Kim HJ, Lee SH, Lim EA, Kim JS. Formulation optimization of solid dispersion of mosapride hydrochloride. Arch Pharm Res. 2011;34(9):1467-1475. DOI: 10.1007/s12272-011-0908-3.

Jahangiri A, Barzegar-Jalali M, Garjani A, Javadzadeh Y, Hamishehkar H, Afroozian A, et al. Pharmacological and histological examination of atorvastatin-PVP K30 solid dispersions. Powder Technol. 2015;286:538-545. DOI: 10.1016/j.powtec.2015.08.047.

Breitenbach J. Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm. 2002;54(2):107-117. DOI: 10.1016/s0939-6411(02)00061-9.

Sarkari M, Brown J, Chen X, Swinnea S, Williams RO 3rd, Johnston KP. Enhanced drug dissolution using evaporative precipitation into aqueous solution. Int J Pharm. 2002;243(1-2):17-31. DOI: 10.1016/s0378-5173(02)00072-8.

Lura A, Luhn O, Suarez Gonzales J, Breitkreutz J. New orodispersible mini-tablets for paediatric use - A comparison of isomalt with a mannitol based co-processed excipient. Int J Pharm. 2019;572:118804,1-35. DOI: 10.1016/j.ijpharm.2019.118804.

Gandhi GP, Mundhada D, Bhaskaran S. Levocetirizine orodispersible tablet by direct compression method. J Appl Pharm Sci. 2011;1:145-150.

Desai PM, Er PXH, Liew CV, Heng PWS. Functionality of disintegrants and their mixtures in enabling fast disintegration of tablets by a quality by design approach. AAPS PharmSciTech. 2014;15(5):1093-1104. DOI: 10.1208/s12249-014-0137-4.

Casian T, Bogdan C, Tarta D, Moldovan M, Tomuţă I, Sonia I. Assessment of oral formulation-dependent characteristics of orodispersible tablets using texture profiles and multivariate data analysis. J Pharm Biomed Anal. 2018;152:47-56. DOI: 10.1016/j.jpba.2018.01.040.

Omar S, AbdAlla F, Abdelgawad N. Effect of mannitol on physical characters of lyophilized fast-disintegrating tablets. J Adv Pharm Res. 2017;1: 228-233. DOI: 10.21608/aprh.2017.4044.


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