INCREASING SOLUTION IN THE DRUG SIMVASTATIN WITH SOLID DISPERSION TECHNIQUE USING POLYMER SOLUPLUS

Authors

  • IYAN SOPYAN Department Pharmaceutics and Technology of Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang-45363, West Java, Indonesia. Center of study Drug Dosage Form Development, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang-45363, West Java, Indonesia. https://orcid.org/0000-0001-7616-5176
  • MUHAMMAD RAIHAN RIYALDI Department Pharmaceutics and Technology of Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang-45363, West Java, Indonesia
  • SORAYA RATNAWULAN MITA Department Pharmaceutics and Technology of Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang-45363, West Java, Indonesia
  • MEYWAN HARIONO Pharmaceutical Design and Simulation Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia-11800, Pulau Pinang, Malaysia https://orcid.org/0000-0001-7616-5176

DOI:

https://doi.org/10.22159/ijap.2023v15i4.48293

Keywords:

Solubility, Dissolution, Simvastatin, Solid dispersion, Soluplus

Abstract

Objective: Simvastatin is a bioactive compound belonging to the class II Biopharmaceutic Classification System (BSC), which has high permeability but low solubility. The low solubility of Simvastatin showed by low bioavailability so modification is required for its solubility.

Methods: There are many techniques to improve the solubility of poorly water-soluble drug; one of them is solid dispersion prepared by the solvent evaporation method. This study aims to determine the solid dispersion formulation of simvastatin using soluplus as a polymer with a ratio of 1:1, 1:2, 1:3, and 1:4 which is employed to increase the solubility and dissolution rate of simvastatin. Furthermore, characterization was carried out using IR spectrophotometry, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD).

Results: The maximum solubility test yielded a 1:4 solid dispersion, which is up to 20 times more potent than pure simvastatin. Simvastatin's solubility increased from 17.33% to 82.50% for a 1:4 solid dispersion at 60 min, affecting the dissolution rate as well.

Conclusion: A solid dispersion was formed in an amorphous state, as evidenced by the fact that the results of characterization using IR spectrophotometry showed no new functional groups were formed in the solid dispersion, the results of characterization using Differential Scanning Calorimetry (DSC) showed a decrease in melting point, and the results of x-ray diffraction characteristics did not show a sharp peak.

Downloads

Download data is not yet available.

References

Alakhali K. Pharmacokinetic of simvastatin study in Malaysian subjects. IOSRPHR. 2013 Jan;3(1):46-51. doi: 10.9790/3013-31104651.

Levin M, editor. Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. In: Informa Healthcare; 2001. Pharmaceutical process scale-up. Available from: http://www.crcnetbase.com doi: 10.1201/9780824741969.

Di L, Kerns E. Drug-like properties: concepts, structure design and methods from ADME to toxicity optimization. Academic press; 2015.

Heart Protection Study Collaborative Group. Effects on 11 y mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 y in 20 536 high-risk individuals: a randomised controlled trial. Lancet. 2011;378(9808):2013-20. doi: 10.1016/S0140-6736(11)61125-2.

Katzung BG, Trevor AJ. Basic and clinical pharmacology; 2012.

Wairkar SM, Gaud RS. Solid dispersions: solubility enhancement technique for poorly soluble drugs. Int J Res Pharm Biomed Sci. 2013;4(3):847.

Singh P, Nanda A. Preparation, characterization and dissolution study of spray dried solid dispersions of simvastatin with PVP k 25 and Aerosil 200. Journal of Medical Pharmaceutical and Allied Sciences. 2021;10(6):3806-12.

Hosny KM, Khames A, Elhady SSA. Preparation and evaluation of orodispersible tablets containing hydroxylbutyl-β-cyclodextrin-simvastatin solid dispersion. Trop J Pharm Res. 2013;12(4):469-76. doi: 10.4314/tjpr.v12i4.4.

Gustaman F. Pengaruh penambahan cremophor El terhadap peningkatan laju disolusi tablet simvastatin. J Pharmacopolium. 2019;2(1). doi: 10.36465/jop.v2i1.471.

Sopyan I, Pallanisamy T, Wardhana YW. Polymorpism of simvastatin: an effort to repair solubility and dissolution rate. Pharm Lett. 2017;9(6):18-27.

Mehmood Y, Hammad Yousaf AK, Bashir I, Majeed I. Preparation and characterization of solid dispersion tablet of simvastatin employing starch phosphate as carrier. International Journal of Chemical and Pharmaceutical Sciences. 2014;5(2):79-84.

Nandi U, Ajiboye AL, Patel P, Douroumis D, Trivedi V. Preparation of solid dispersions of simvastatin and Soluplus using a single-step organic solvent-free supercritical fluid process for the drug solubility and dissolution rate enhancement. Pharmaceuticals (Basel). 2021;14(9):846. doi: 10.3390/ph14090846, PMID 34577546.

Compendium S. Solubility enhancement with BASF pharma polymers. Lampertheim, Germany: Pharma Ingredients and Services; 2011.

Zhu C, Gong S, Ding J, Yu M, Ahmad E, Feng Y. Supersaturated polymeric micelles for oral silybin delivery: the role of the Soluplus–PVPVA complex. Acta Pharm Sin B. 2019;9(1):107-17. doi: 10.1016/j.apsb.2018.09.004, PMID 30766782.

Zi P, Zhang C, Ju C, Su Z, Bao Y, Gao J. Solubility and bioavailability enhancement study of lopinavir solid dispersion matrixed with a polymeric surfactant–soluplus. Eur J Pharm Sci. 2019;134:233-45. doi: 10.1016/j.ejps.2019.04.022, PMID 31028820.

Prasad R, Radhakrishnan P, Singh SK, Verma PRP. Furosemide–soluplus® solid dispersion: development and characterization. Recent Pat Drug Deliv Formul. 2017;11(3):211-20. doi: 10.2174/1872211311666171129120020, PMID 29189186.

Hardung H, Djuric D, Ali S. Combining HME and solubilization: Soluplus®-the solid solution. Drug Deliv Technol. 2010;10(3):20-7.

Shamma RN, Basha M. Soluplus®: A novel polymeric solubilizer for optimization of carvedilol solid dispersions: formulation design and effect of method of preparation. Powder Technol. 2013 Mar;237:406-14. doi: 10.1016/j.powtec.2012.12.038.

Chiou WL, Riegelman S. Pharmaceutical applications of solid dispersion systems. J Pharm Sci. 1971;60(9):1281-302. doi: 10.1002/jps.2600600902, PMID 4935981.

Pokharkar VB, Mandpe LP, Padamwar MN, Ambike AA, Mahadik KR, Paradkar A. Development, characterization and stabilization of amorphous form of a low Tg drug. Powder Technol. 2006;167(1):20-5. doi: 10.1016/j.powtec.2006.05.012.

Karavas E, Ktistis G, Xenakis A, Georgarakis E. Effect of hydrogen bonding interactions on the release mechanism of felodipine from nanodispersions with polyvinylpyrrolidone. Eur J Pharm Biopharm. 2006;63(2):103-14. doi: 10.1016/j.ejpb.2006.01.016, PMID 16675209.

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):1068-75. doi: 10.1016/j.drudis.2007.09.005, PMID 18061887.

Harmita H. Buku ajar analisis fisikokimia. Jakarta dep farm FMIPA ui. UI Press. 2006:120-3.

Zhang Y, Liu Y, Luo Y, Yao Q, Zhong Y, Tian B, et al. Extruded Soluplus/SIM as an oral delivery system: characterization, interactions, in vitro and in vivo evaluations. Drug Deliv. 2016;23(6):1902-11. doi: 10.3109/10717544.2014.960982, PMID 25268150.

Lobmann K, Strachan C, Grohganz H, Rades T, Korhonen O, Laitinen R. Co-amorphous simvastatin and glipizide combinations show improved physical stability without evidence of intermolecular interactions. Eur J Pharm Biopharm. 2012;81(1):159-69. doi: 10.1016/j.ejpb.2012.02.004, PMID 22353489.

Aakeroy CB, Fasulo ME, Desper J. Cocrystal or salt: does it really matter? Mol Pharm. 2007;4(3):317-22. doi: 10.1021/mp060126o, PMID 17497799.

Zaini E, Halim A, Soewandhi SN, Setyawan D. Peningkatan laju pelarutan trimetoprim melalui metode ko-kristalisasi dengan nikotinamida. J Farmasi Indones. 2011;5(4):205-12.

Mulye SP, Jamadar SA, Karekar PS, Pore YV, Dhawale SC. Improvement in physicochemical properties of ezetimibe using a crystal engineering technique. Powder Technol. 2012;222:131-8. doi: 10.1016/j.powtec.2012.02.020.

Mishra MK, Ray D, Barik BB. Microcapsules and transdermal patch: a comparative approach for improved delivery of antidiabetic drug. AAPS PharmSciTech. 2009;10(3):928-34. doi: 10.1208/s12249-009-9289-z, PMID 19629706.

Gracin S, Rasmuson AC. Solubility of phenylacetic acid, p-hydroxyphenylacetic acid, p-aminophenylacetic acid, p-hydroxybenzoic acid, and Ibuprofen in Pure Solvents. J Chem Eng Data. 2002;47(6):1379-83. doi: 10.1021/je0255170.

Sopyan I, Sari IM, K IS. Solid state characterization of a novel physical interaction (paracetamol-chlorphenoramine maleate). Int J Appl Pharm. 2018;6:21-5.

Sopyan I, Fudholi A, Muchtaridi M, Puspitasari I. A simple effort to enhance solubility and dissolution rate of simvastatin using co-crystalization. Int J Pharm Pharm Sci. 2016;8(8):342-6.

Published

07-07-2023

How to Cite

SOPYAN, I., RIYALDI, M. R., MITA, S. R., & HARIONO, M. (2023). INCREASING SOLUTION IN THE DRUG SIMVASTATIN WITH SOLID DISPERSION TECHNIQUE USING POLYMER SOLUPLUS. International Journal of Applied Pharmaceutics, 15(4), 160–165. https://doi.org/10.22159/ijap.2023v15i4.48293

Issue

Section

Original Article(s)

Most read articles by the same author(s)

<< < 1 2 3