Enhancement of dissolution of atorvastatin through preparation of polymeric solid dispersions using supercritical fluid technology

Bashar Altaani , Rana Obaidat, Walaa Malkawi


Background and purpose: This study aimed at preparation of solid dispersions in order to enhance dissolution of poorly water-soluble atorvastatin using supercritical CO2 technology. Atorvastatin has poor bioavailability of 12%, mainly due to poor water solubility and dissolution. Dispersion of drugs in various hydrophilic carriers using supercritical fluid technology has been found to be an outstanding method to prepare solid dispersion.

Experimental approach: Four different polymers were employed. These were polyvinyl pyrrolidone K30 (PVP), polyethylene glycol 6000 (PEG), Soluplus®, and chitosan. Full physicochemical characterizations were performed in addition to in vitro dissolution study.

Findings / Results: The used polymers enhanced the dissolution rate of atorvastatin. However, supercritical parameters affected the dissolution profile and drug loading efficiency of the prepared dispersions. High performance liquid chromatography assay indicated the stability of the prepared PEG, Soluplus® and chitosan-based dispersions. On the other hand, PVP solid dispersions were not stable and formed sticky paste. Powder X-ray diffraction showed similar patterns for PEG-based dispersions after exposure to storage condition, while the intensity of atorvastatin peaks increased after three months of storage of Soluplus® and chitosan dispersions.

Conclusion and implications: Supercritical fluid technology proved to have great potential to prepare dispersions for biopharmaceutics classification system (BCS) class II drugs. Dissolution enhancement of atorvastatin was achieved through successful preparation of polymeric dispersions of the drug using the supercritical technology without further addition of solvents.



Atorvastatin; Solublity enhancement; Polyethylene glycol; Solid dispersions; Soluplus; Supercritical fluid technology.

Full Text:



Badens E, Majerik V, Horvath G, Szokonya L, Bosc N, Teillaud E, et al. Comparison of solid dispersions produced by supercritical antisolvent and spray-freezing technologies. Int J Pharm. 2009;377(1-2):25-34.

DOI: 10.1016/j.ijpharm.2009.04.047.

Obaidat RM, Tashtoush BM, Bayan MF, Al Bustami RT, Alnaief M. Drying using supercritical fluid technology as a potential method for preparation of chitosan aerogel microparticles. AAPS PharmSciTech. 2015;16(6):1235-1244.

DOI: 10.1208/s12249-015-0312-2.

Maniruzzaman M, Boateng JS, Snowden MJ, Douroumis D. A Review of hot-melt extrusion: process technology to pharmaceutical products. ISRN Pharm. 2012;2012:436763-436771.

DOI: 10.5402/2012/436763.

Kamalakkannan V, Puratchikody A, Ramanathan L. Development and characterization of controlled release polar lipid microparticles of candesartan cilexetil by solid dispersion. Res Pharm Sci. 2013;8(2):125-136.

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

Dixit M, Kini AG, Kulkarni PK. Preparation and characterization of microparticles of piroxicam by spray drying and spray chilling methods. Res Pharm Sci. 2010;5(2):89-97.

Tabbakhian M, Hasanzadeh F, Tavakoli N, Jamshidian Z. Dissolution enhancement of

glibenclamide by solid dispersion: solvent evaporation versus a supercritical fluid-based solvent -antisolvent technique. Res Pharm Sci. 2014;9(5):337-350.

Obaidat RM, Tashtoush BM, Awad AA, Al Bustami RT. Using supercritical fluid technology (SFT) in preparation of tacrolimus solid dispersions. AAPS PharmSciTech. 2017;18(2):481-493.

DOI: 10.1208/s12249-016-0492-4.

Vo CL, Park C, Lee BJ. Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J Pharm Biopharm. 2013;85(3 Pt B):799-813.

DOI: 10.1016/j.ejpb.2013.09.007.

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;237:406-414.

DOI: 10.1016/j.powtec.2012.12.038.

Maestrelli F, Zerrouk N, Chemtob C, Mura P. Influence of chitosan and its glutamate and hydrochloride salts on naproxen dissolution rate and permeation across Caco-2 cells. Int J Pharm. 2004;271(1-2):257-267.

DOI: 10.1016/j.ijpharm.2003.11.024.

Zhong L, Zhu X, Luo X, Su W. Dissolution properties and physical characterization of telmisartan-chitosan solid dispersions prepared by mechanochemical activation. AAPS PharmSciTech. 2013;14(2):541-550. DOI: 10.1208/s12249-013-9937-1.

Hu L, Gu D, Hu Q, Shi Y, Gao N. Investigation of solid dispersion of atorvastatin calcium in polyethylene glycol 6000 and polyvinylpyrrolidone. Trop J Pharm Res. 2014;13(6):835-842.

DOI: 10.4314/tjpr.v13i6.2.

Yin YM, Cui FD, Kim JS, Choi MK, Choi BC, Chung SJ, et al. Preparation, characterization and in vitro intestinal absorption of a dry emulsion formulation containing atorvastatin calcium. Drug Deliv. 2009;16(1):30-36.

DOI: 10.1080/10717540802481380.

Ha ES, Baek IH, Cho W, Hwang SJ, Kim MS. Preparation and evaluation of solid dispersion of atorvastatin calcium with soluplus(R) by spray drying technique. Chem Pharm Bull (Tokyo). 2014;62(6):545-551.

DOI: 10.1248/cpb.c14-00030.

Kim JS, Kim MS, Park HJ, Jin SJ, Lee S, Hwang SJ. Physicochemical properties and oral bioavailability of amorphous atorvastatin hemi-calcium using spray-drying and SAS process. Int J Pharm. 2008;359(1-2):211-219.

DOI: 10.1016/j.ijpharm. 2008.04.006.

Aggarwal S, Gupta GD, Chaudhary S. Solubility and dissolution enhancement of poorly aqueous soluble drug atorvastatin calcium using modified gum karaya as carrier: in vitro-in vivo evaluation. Int J Drug Deliv. 2012;4(3):341-365.

DOI: 10.5138/ijdd.v4i3.75.

Lakshmi Narasaiah L, Kalyan Reddy K, Kishore K, Raj Kumar R, Srinivasa Rao S, Venkateswara Reddy V. Enhanced dissolution rate of atorvastatin calcium using solid dispersion with PEG 6000 by dropping method. J Pharm Sci & Res. 2010;2(8):484-491.

Qandil AM, Obaidat AA, Mohammed Ali MA, Al-Taani BM, Tashtoush BM, Al-Jbour ND, et al. Investigation of the interactions in complexes of low molecular weight chitosan with ibuprofen. J Solution Chem. 2009;38(6):695-712.

DOI: 10.1007/s10953-009-9405-4.

Obaidat R, Al-Jbour N, Al-Sou’d K, Sweidan K, Al-Remawi M, Badwan A. Some physico-chemical properties of low molecular weight chitosans and their relationship to conformation in aqueous solution. J Solution Chem. 2010;39(4):575-588. DOI: 10.1007/s10953-010-9517-x.

Shen H, Zhong M. Preparation and evaluation of self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin. J Pharm Pharmacol. 2006;58(9):1183-1191.

DOI: 10.1211/ jpp.58.9.0004.

Lee JY, Kang WS, Piao J, Yoon IS, Kim DD, Cho HJ. Soluplus(R)/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan. Drug Des Devel Ther. 2015;9:2745-2756. DOI: 10.2147/DDDT.S84070.

Ioelovich M. Crystallinity and hydrophility of chitin and chitosan. Res Rev: J Chem. 2014;3(3):7-14.

Lv HX, Zhang ZH, Jiang H, Waddad AY, Zhou JP. Preparation, physicochemical characteristics and bioavailability studies of an atorvastatin hydroxypropyl-beta-cyclodextrin complex. Pharmazie. 2012;67(1):46-53.

DOI: 10.1691/ph.2012.1082.

Patil MP, Gaikwad NJ. Characterization of gliclazide-polyethylene glycol solid dispersion and its effect on dissolution. Braz J Pharm Sci. 2011;47(1):161-166.

DOI: 10.1590/S1984-82502011000100020.

Bathool A, Vishakante GD, Khan MS, Shivakumar HG. Development and characterization of atorvastatin calcium loaded chitosan nanoparticles for sustain drug delivery. Adv Mat Lett. 2012;3(6):466-470.

DOI: 10.5185/amlett.2012.icnano.153.

Abd El-kader M, Abu-Abdeen M. Thermal and mechanical studies of PVP/2-HEC blend films. Aust J Basic & Appl Sci. 2012;6(13):454-462.

Terife G, Wang P, Faridi N, Gogos CG. Hot melt mixing and foaming of soluplus® and indomethacin. Polym Eng Sci. 2012;52(8):1629-1639.

DOI: 10.1002/pen.23106.

Rende D, Schadler LS, Ozisik R. Controlling foam morphology of poly(methyl methacrylate) via surface chemistry and concentration of silica nanoparticles and supercritical carbon dioxide process parameters. J Chem. 2013;2013:864926,1-13.

DOI: 10.1155/2013/864926.

Caron V, Hu Y, Tajber L, Erxleben A, Corrigan O, McArdle P, et al. Amorphous solid dispersions of sulfonamide/soluplus® and sulfonamide/PVP srepared by ball milling. AAPS PharmSciTech. 2013;14(1):464-474.

DOI: 10.1208/s12249-013-9931-7.

Obaidat RM, Tashtoush BM, Awad AA, Al Bustami RT. Using supercritical fluid technology (SFT) in preparation of tacrolimus solid dispersions. AAPS PharmSciTech. 2017;18(2):481-493.

DOI: 10.1208/s12249-016-0492-4.

Roohullah, Iqbal Z, Nasir F, Akhlaq M, Sadozai SK, Zada A, et al. Sustained release carbamezapine matrix tablets prepared by solvent-evaporation technique using different polymers. Middle East J Sci Res. 2013;15(10):1368-1374.

DOI: 10.5829/idosi.mejsr.2013.15.10.7553.

Shoaib MH, Tazeen J, Merchant HA, Yousuf RI. Evaluation of drug release kinetics from ibuprofen matrix tablets using HPMC. Pak J Pharm Sci. 2006;19(2):119-124.

Parize A, Stulzer H, Laranjeira M, Brighente I, Souza T. Evaluation of chitosan microparticles containing curcumin and crosslinked with sodium tripolyphosphate produced by spray drying. Quim Nova. 2012;35(6):1127-1132.

DOI: 10.1590/S0100-40422012000600011.

Shah I, Bhatt S, Yadav A. Enhancement of solubility and dissolution of nebivolol by solid dispersion technique. Int J Pharm Pharm Sci. 2014;6(7):566-571.

Sambath L, Muthu AK, Kumar MA. Soluplus complexation influence the release of lovastatin from porous osmotic pump tablet. World J Pharm Pharm Sci. 2013;2(5):3506-3521.

Zou X, Zhao X, Ye L, Wang Q, Li H. Preparation and drug release behavior of pH-responsive bovine serum albumin-loaded chitosan microspheres. J Ind Eng Chem. 2015;21:1389-1397.

DOI: 10.1016/j.jiec. 2014.06.012.


  • There are currently no refbacks.

Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.