Improvement of Solubility and Dissolution Rate of Poorly Water-Soluble Anti-Cholestermic Drug Atorvastatin by Solid Dispersion Technique

DOI:

https://doi.org/10.37285/ijpsn.2020.13.1.8

Authors

  • Ramya Patnala
  • Shiny Pauline
  • Tayyaba Mahtab
  • Sumaiyya Saleem Saleem
  • Abrar Abrar
  • Reena Sowmya P

Abstract

Atorvastatin calcium belongs to class II drug, which is characterized by low solubility and high permeability, which makes the drug to have low bioavailability. Enhancement of its solubility makes the drug more bioavailable and has fewer side effects. This was achieved by forming solid dispersion of the drug and formulating the tablets. Atorvastatin was mixed with various proportions of excipients which showed no color change at the end of two months, proving no drug-excipient interaction as confirmed by FTIR studies. The pre-compression blend of atorvastatin solid dispersions which were prepared by solvent evaporation technique were characterized with respect to angle of repose, bulk density, tapped density, Carr’s index and Hausner’s ratio. The pre-compression blends of all the batches were showed good to fair flowability and compressibility especially with F2 formulation having excellent results. The prepared formulations were evaluated for various quality control parameters. The tablets formulations passed all the tests of post formulation studies such as weight variation, friability, drug content, etc. From the in vitro studies, among all the formulations F2 formulation containing drug and mannitol in the ratio of 1:2 showed good dissolution rate of 97.43% in 25 minutes. While the formulations containing PVP k30 and PEG 4000 showed less release. Therefore, F2 formulation was found to be the better formulation as per dissolution profile. By conducting further studies like preclinical and clinical, the formulation can be adopted for manufacturing in bulk.

 

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Keywords:

Atorvastatin, solid dispersions, Mannitol, PEG 4000, PVP k30

Downloads

Published

2020-01-31

How to Cite

1.
Patnala R, Pauline S, Mahtab T, Saleem SS, Abrar A, P RS. Improvement of Solubility and Dissolution Rate of Poorly Water-Soluble Anti-Cholestermic Drug Atorvastatin by Solid Dispersion Technique. Scopus Indexed [Internet]. 2020 Jan. 31 [cited 2024 Dec. 22];13(1):4787-92. Available from: https://ijpsnonline.com/index.php/ijpsn/article/view/254

Issue

Section

Research Articles

References

Ahjel SW and Lupuleasa D (2009). Enhancement of solubility and dissolution rate of different forms of atorvastatin calcium in direct compression tablet formulas. Farmacia 57(3): 290-300.
Arunkumar N, Rani C and Mohanraj KP (2008). Formulation and in vitro evaluation of oral floating tablets of atorvastatin calcium. Research Journal of Pharmacy and Technology 1(4): 492-5.
Choudhary A, Rana AC, Aggarwal G, Kumar V and Zakir F (2012). Development and characterization of an atorvastatin solid dispersion formulation using skimmed milk for improved oral bioavailability. Acta Pharmaceutica Sinica B 2(4): 421-8.
Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V and Fuller JH (2004). Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. The Lancet 364(9435): 685-96.
Gomez‐Dominguez E, Gisbert JP, Moreno‐Monteagudo JA, Garcia‐Buey L and MorenoOtero R (2006). A pilot study of atorvastatin treatment in dyslipemid, non-alcoholic fatty liver patients. Alimentary pharmacology & therapeutics 23(11): 1643-7.
Gupta A, Sehgal V and Mehan S (2011). Hyperlipidemia: An updated review. International Journal of Biopharmaceutical Toxicological Research 1: 81-9.
Huang Y and Dai WG (2014). Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta Pharmaceutica Sinica B 4(1):18-25.
Karam JG, Loney-Hutchinson L and McFarlane SI (2008). High-dose atorvastatin after stroke or transient ischemic attack: the stroke prevention by aggressive reduction in cholesterol levels (SPARCL) investigators. Journal Cardiometabolic Syndrome 3(1): 68-69.
Karpisek M, Stejskal D, Kotolova H, Kollar P, Janoutova G, Ochmanova R, Cizek L, Horakova D, Yahia RB, Lichnovska R, and Janout V (2007). Treatment with atorvastatin reduces serum adipocyte‐fatty acid binding protein value in patients with hyperlipidaemia. European Journal of Clinical Investigation. 37(8): 637-642.
Khan FN, Dehghan MH (2011). Enhanced bioavailability of atorvastatin calcium from stabilized gastric resident formulation. AAPS Pharm Sci Tech 12(4): 1077-86.
Marchesi S, Lupattelli G, Siepi D, Schillaci G, Vaudo G, Roscini AR, Sinzinger H, and Mannarino E (2000). Short-term atorvastatin treatment improves endothelial function in hypercholesterolemic women. Journal of cardiovascular pharmacology 36(5): 617-21.
Mohindeen S, Jyothi B, Pavani S, Satyanarayana T, Kumar SP, Krishna NS (2011). Formulation and evaluation of bilayered tablets of metformin hydrochloride and atorvastatin calcium. Int J Pharm Sci Rev Res 10(2): 130-4.
Nirmal J, Saisivam S, Peddanna C, Muralidharan S, Godwinkumar S, Nagarajan M (2008). Bilayer tablets of atorvastatin calcium and nicotinic acid: formulation and evaluation. Chemical and Pharmaceutical Bulletin 56(10): 1455-8.
Pontrelli L, Parris W, Adeli K, and Cheung RC (2002). Atorvastatin treatment beneficially alters the lipoprotein profile and increases low-density lipoprotein particle diameter in patients with combined dyslipidemia and impaired fasting glucose/type 2 diabetes. Metabolism-Clinical and Experimental 51(3): 334-42.
Ross R, Harker L (1976). Hyperlipidemia and atherosclerosis. Science 193(4258): 1094-100.
Roth BD (2002). The Discovery and Development of Atorvastatin, a Potent Novel Hypolipidemic Agent. Progress in Medicinal Chemistry 40: 1-22.
Sasaki S, Kuwahara N, Kunitomo K, Harada S, Yamada T, Azuma A, Takeda K, and Nakagawa M (2002). Effects of atorvastatin on oxidized low-density lipoprotein, low-density lipoprotein subfraction distribution, and remnant lipoprotein in patients with mixed hyperlipoproteinemia. The American Journal of Cardiology 89(4): 386-9.
Sarfraz RM, Khan HU, Mahmood A, Ahmad M, Maheen S, Sher M (2015). Formulation and evaluation of mouth disintegrating tablets of atenolol and atorvastatin. Indian Journal of Pharmaceutical Sciences 77(1): 83.
Serajuddin AT (1999). Solid dispersion of poorly water-soluble drugs: Early promises, subsequent problems, and recent breakthroughs. Journal of Pharmaceutical Sciences 88(10): 1058-1066.
Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT and Mehlsen J (2003). Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. The Lancet 361(9364):1149-58.
Tousoulis D, Oikonomou E, Siasos G, Chrysohoou C, Zaromitidou M, Kioufis S, Maniatis K, Dilaveris P, Miliou A, Michalea S, and Papavassiliou AG (2013). Dose-dependent effects of short- term atorvastatin treatment on arterial wall properties and on indices of left ventricular remodeling in ischemic heart failure. Atherosclerosis 227(2): 367-372.
van Wissen S, Smilde TJ, Trip MD, Stalenhoef AF and Kastelein JJ (2005). Long-term safety and efficacy of high-dose atorvastatin treatment in patients with familial hypercholesterolemia. The American journal of cardiology 95(2): 264-266.
Yang YJ, Qian HY, Huang J, Geng YJ, Gao RL, Dou KF, Yang GS, Li JJ, Shen R, He ZX, and Lu MJ (2008). Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts. European heart journal 29(12): 1578-90.