Pharm Sci. 2020;26(1): 61-74.
doi: 10.34172/PS.2019.52

Scopus ID: 85084567978
  Abstract View: 330
  PDF Download: 225

Research Article

Response Surface Methodology for Optimization of Process Variables of Atorvastatin Suspension Preparation by Microprecipitation Method Using Desirability Function

Maryam Maghsoodi 1,2 ORCID logo, Seyed hassan Montazam 3, Hossein Rezvantalab 4, Mitra Jelvehgari 1,2* ORCID logo

1 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Department of Microbiology, Bonab Branch, Islamic Azad University, Bonab, Iran.
4 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.


Background: Atorvastatin (AT), as a synthetic lipid-lowering agent, is a highly crystalline substance having poor solubility and low bioavailability. The objective of the present research was to improve the microprecipitation method of AT suspension preparation.

Methods: Microprecipitation parameters were improved using Box-Behnken experimental design method. The suspension was formulated with Brij 35 (stabilizer agent) using methanol as solvent and water as non-solvent, respectively. DSC, XRD, FTIR studies were performed for characterization of the microcrystals. With the aim of evaluating the effect of independent variables, the amounts of organic solvent (X1), emulsifier concentration (X2), stirring rate (X3), and volume of aqueous solvent (X4) on dependent variables, drug content (DC,) particle size (PS), drug released after 5 minutes (Q5), Gibbs free energy change (ΔG°tr), crystal yield (CY) and saturated solubility (Ss), a full factorial was used.

Results: The results of DSC, XRD, and FTIR showed that there was not any interaction between AT and Brij 35. This research demonstrated a reduction in crystallinity in agglomerates. The microcrystals showed that micromeritics characteristics were significantly improved compared to pure AT. The content of drug and yield crystal was in the limit of 42.58-110.24% and 58.33-98.18% in all formulations, respectively. It was shown that the prepared microcrystals had a higher rate of release compared to the untreated AT powder (P< 0.05). Size reduction of AT is needed for improving the solubility. Solubility and drug release rates of At was enhanced with the microprecipitation method.

Conclusion: The results showed that microcrystals significantly increased AT dissolution rate.

Keywords: Atorvastatin, Suspension, Microprecipitation, Box-Behnken Method, Brij 35, Microcrystal
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Submitted: 21 Jul 2019
Revision: 29 May 2019
Accepted: 29 May 2019
ePublished: 10 Mar 2020
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