Abstract
Purpose: To develop and validate a novel reverse phase high performance liquid chromatographic (RP-HPLC) method for the quantification of atorvastatin in thermosensitive hydrogel-based nanocrystal formulation.Method: Chromatographic identification was achieved on C18 (5 μm) column using acetonitrile and 0.025 M potassium dihydrogen ortho-phosphate buffer pH 5 (45:55 v/v) as mobile phase, at a flow rate of 1.5 mL/min and using photo diode array detector (PDA) at 246 nm. The developed HPLC method was validated according to International Conference on Harmonisation (ICH) Q2(R1) guidelines and applied to dissolution studies on atorvastatin thermosensitive hydrogel-based nanocrystal formulation, using Lipitor® as standard.Results: Determination was successfully achieved with good peak resolution from atorvastatin nanocrystals and a commercial formulation brand (Lipitor® tablets) without interference of polymer or excipients. The retention time of atorvastatin was 4.5 min and drug response was linear in the range of 0.1 - 0.5 μg/mL with a correlation coefficient of 0.9995. Precision was determined to be between 0.16 - 0.61 percent relative standard deviation (% RSD) for the analyzed samples. The limit of detection and of quantification was 35.6 and 71.2 ng/mL, respectively, which was 10 times higher than a previously reported method. The assay of atorvastatin nanocrystal and Lipitor® gave 99.37 and 99.12 % recovery, respectively. Dissolution studies showed atorvastatin release of 40 and 65 % at 40 min from thermosensitive hydrogel nanocrystal formulation and Lipitor®, respectively indicating sustained release.Conclusion: The method is successfully validated and is specific, linear, precise, and accurate with good robustness. It is applicable to atorvastatin nanocrystal dissolution studies and is a promising quality control tool for atorvastatin analysis in nanoformulations and pharmaceutical dosage forms.Keywords: Atorvastatin, Anticholestermic, Dissolution studies, Hydrogel, Nanocrystal, Thermosensitive
Highlights
Atorvastatin [(3R, 5R)-7-[2-(4-fluorophenyl)-3phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol1-yl]-3, 5-dihydroxyheptanoic acid] calcium is one of the seven often-administered statins, belonging to the anti-hyperlipidemic class of drugs [1]
The optimal conditions considered for mobile phase were 45:55 v/v ratio of acetonitrile to 0.025 M potassium dihydrogen orthophosphate buffer at pH 5, which gave a sharp symmetric peak at a flow rate of 1.50 rpm. Aliquots (5 mL)/min
C18 column was chosen for its high hydrophobicity over C8, so that atorvastatin was eluted faster at a lower flow rate and retention time
Summary
Atorvastatin [(3R, 5R)-7-[2-(4-fluorophenyl)-3phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol1-yl]-3, 5-dihydroxyheptanoic acid] calcium is one of the seven often-administered statins, belonging to the anti-hyperlipidemic class of drugs [1]. The drug is reported to have poor solubility leading to low absolute and systemic bioavailability of about 14 and 30 %, respectively [7,8]. Modified or prolonged release delivery systems for atorvastatin are not available except for Selfnano emulsifying drug delivery systems (SNEDDS) [9]. Nanocrystals possess high entrapment efficiency, with enhanced solubility and drug bioavailability [10]. The release modification of drugs by incorporation of nanocrystals into a thermosensitive polymer matrix is very innovative, and assay of atorvastatin along with other excipients within nanoformulation is challenging as well [11]
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