• SARAH LABIB Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Misr International University, Cairo, Egypt
  • MOHAMED NASR Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo, Egypt
  • MOHAMED NASR Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Misr International University, Cairo, Egypt


Objective: The main objective of this study was to develop atorvastatin calcium (ATR) as an oral drug delivery system for a P-glycoprotein (P-gp) substrate drug using different pharmaceutical excipients that inhibit P-glycoprotein and evaluate the influence of nanocrystals on the dissolution characteristics and bioavailability compared to the plain drug.

Methods: A nanosuspension was prepared by Solvent-antisolvent precipitation method using a solvent containing stabilizer that act as a p-gp inhibitor dissolved in distilled water as polyethylene glycol 300, polyethylene glycol 400 (PEG 300, PEG 400), tween 20 and tween 80 while the solvent selected for atorvastatin calcium was methanol. The concentrations were as follows: PEG 300 and 400 = 0.25% w/v, tween 20 and 80 = 0.75% v/v. Nanocrystals were extracted from the suspension and characterized.

Results: Particle size of the drug was 1307±127.79 nm while the formulas prepared ranged from 223±17.67 to 887±58.12 nm. Pure ATR had a saturated solubility of 0.059±0.005 mg/ml and the prepared nanocrystals ranged from 0.32±0.021 to 0.88±0.019 mg/ml. The Percentage of drug released of plain atorvastatin calcium reached 41.49% while the formula ranged from 44.32 to 61.5%. Both XRD and SEM discussed the degree of crystallinity as follows: F1<F2<F4<F3<ATR.

Conclusion: 0.3% of PEG 300 and PEG 400 were not enough to formulate proper nanocrystals while 0.75% tween 20 and tween 80 achieved acceptable formulas. F4 which is prepared with tween 80 exhibited the highest enhancement in saturated solubility, dissolution rate and subsequently expected to have improved oral bioavailability.

Keywords: Atorvastatin Calcium, Nanocrystals, Antisolvent Precipitation Method, Solubility, Bioavailability, P-glycoprotein


1. Maiti SJJoPST. Liquid-crystal and nano-crystal technology for solubilization of poorly water-soluble drugs. J PharmSciTech 2012;2:1-4.
2. Sareen S, Mathew G, Joseph LJIjopi. Improvement in solubility of poor water-soluble drugs by solid dispersion. Int J Pharm Investig 2012;2:12-7.
3. Zhang L, Webster TJJNt. Nanotechnology and nanomaterials: promises for improved tissue regeneration. Nano today 2009;4:66-80.
4. Desu PK, Sindhuja M, Thriveni K, Nagalakshmi V, Rao PVJWJPPS. A review on the significance of nanocrystals in drug delivery. World J Pharm Pharm Sci 2017;6:347-58.
5. Koh KK, Quon MJ, Waclawiw MAJA. Are statins effective for simultaneously treating dyslipidemias and hypertension? Atherosclerosis 2008;196:1-8.
6. Elmowafy M, Ibrahim H, Ahmed M, Shalaby K, Salama A, Hefesha H. Atorvastatin-loaded nanostructured lipid carriers (NLCs): strategy to overcome oral delivery drawbacks. Drug Delivery 2017;24:932-41.
7. Khan FN, Dehghan MHGJAP. Enhanced bioavailability of atorvastatin calcium from the stabilized gastric resident formulation. AAPS PharmSciTech 2011;12:1077-86.
8. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MCJPotNAoS. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 1987;84:7735-8.
9. Leveque D, Jehl FJAr. P-glycoprotein and pharmacokinetics. Anticancer Res 1995;15:331-6.
10. de Paiva Lacerda S, Espitalier F, Hoffart V, Re MIJDd, Pharmacy I. Liquid anti-solvent recrystallization to enhance dissolution of CRS 74, a new antiretroviral drug. Drug Dev Industrial Pharm 2015;41:1910-20.
11. Zhang H, Yao M, Morrison RA, Chong SJAopr. Commonly used surfactant, Tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats. 2003;26:768-72.
12. Chin SF, Mohd Yazid SNA, Pang SCJIJoPS. Preparation and characterization of starch nanoparticles for controlled release of curcumin. Int J Polymer Sci 2014.
13. Jukanti R, Sheela S, Bandari S, Veerareddy PRJJops. Enhanced bioavailability of exemestane via proliposomes based transdermal delivery. J Pharm Sci 2011;100:3208-22.
14. Nasr MJAP. Influence of microcrystal formulation on in vivo absorption of celecoxib in rats. AAPS PharmSciTech 2013;14:719-26.
15. Rodde MS, Divase GT, Devkar TB, Tekade ARJBri. Solubility and bioavailability enhancement of poorly aqueous soluble atorvastatin: in vitro, ex vivo, and in vivo studies. Biomed Res Int 2014. DOI:10.1155/2014/463895
16. Hecq J, Deleers M, Fanara D, Vranckx H, Amighi KJIjop. Preparation and characterization of nanocrystals for solubility and dissolution rate enhancement of nifedipine. Int J Pharm 2005;299:167-77.
17. Rahat Jahan M, Islam S, Tanwir A, Chowdhury JAJJoapt, Research. In vitro dissolution study of atorvastatin binary solid dispersion. J Adv Pharm Technol Res 2013;4:18.
18. Arunkumar N, Deecaraman M, Rani C, Mohanraj K, Kumar KVJIJPTR. Preparation and solid-state characterization of atorvastatin nanosuspensions for enhanced solubility and dissolution. Int J PharmTech Res 2009;1:1725-30.
19. Masarudin MJ, Cutts SM, Evison BJ, Phillips DR, Pigram PJJN, Science, Applications. Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of 14C-doxorubicin. Nanotechnol Sci Appl 2015;8:67.
20. Choudhary A, Rana AC, Aggarwal G, Kumar V, Zakir FJAPSB. Development and characterization of an atorvastatin solid dispersion formulation using skimmed milk for improved oral bioavailability. Acta Pharm Sin B 2012;2:421-8.
21. Behera A, Sahoo S, Patil SJDPL. Enhancement of solubility: a pharmaceutical overview. Pharm Lett 2010;2:310-8.
22. Rasenack N, Müller BWJPr. Dissolution rate enhancement by in situ micronization of poorly water-soluble drugs. Pharm Res 2002;19:1894-900.
23. Sharma M, Mehta I. Surface stabilized atorvastatin nanocrystals with improved bioavailability, safety and antihyperlipidemic potential. Scientific Reports 2019;9:16105.
24. Panghal D, Nagpal M, Thakur GS, Arora SJSp. Dissolution improvement of atorvastatin calcium using modified locust bean gum by the solid dispersion technique. Pharm Res 2014;82:177-92.
25. Zhong J, Shen Z, Yang Y, Chen JJIjop. Preparation and characterization of uniform nanosized cephradine by the combination of reactive precipitation and liquid anti-solvent precipitation under high gravity environment. Int J Pharm 2005;301:286-93.
26. Zhang HX, Wang JX, Zhang ZB, Le Y, Shen ZG, Chen JFJIjop. Micronization of atorvastatin calcium by antisolvent precipitation process. Int J Pharm 2009;374:106-13.
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How to Cite
LABIB, S., M. NASR, and M. NASR. “FORMULATION AND EVALUATION OF ATORVASTATIN CALCIUM NANOCRYSTALS CONTAINING P-GLYCOPROTEIN INHIBITORS FOR ENHANCING ORAL DELIVERY”. International Journal of Current Pharmaceutical Research, Vol. 13, no. 3, May 2021, pp. 19-23, doi:10.22159/ijcpr.2021v13i3.42087.
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