Inclusion complexes of atorvastatin calcium–sulfobutyl ether β cyclodextrin with enhanced hypolipidemic activity
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Date
2019-11
Journal Title
Journal ISSN
Volume Title
Publisher
Open Science Publishers LLP
Abstract
The aim of present study was to explore the impact of Atorvastatin (ATR) Sulfobutylether beta-cyclodextrin complex(ATR-SBE-β-CD) on ATR dissolution behavior. Various batches of inclusion complexes were formulated usingvarious drug: polymer ratios (1:1, 1:3, and 1:5); using β-CD and SBE-β-CD and using two methods (freeze dryingand kneading method). Phase solubility studies were carried out of all the complexes and ratio 1:5 (ATR-SBE-β-CD)prepared by freeze-drying yield maximum solubility enhancement (30-fold in comparison to pure drug). Fouriertransformation infrared spectroscopy, Powder X-ray diffraction, Scanning electron microscopy (SEM), Differentialscanning calorimetry (DSC) studies was also carried out. FTIR studies showed no drug polymer interaction. DSCand SEM studies suggested incorporation of drug into inclusion complexes of cyclodextrin. Solid dispersion viaFreeze drying technique using SBE-β-CD (1:3 ratio of drug to polymer) produces better dissolution characteristics incomparison to kneading method. The results revealed superiority of SBE-β-CD over β-CD for solubility enhancementof poorly soluble drugs (owing to amorphous nature and more stable form of SBE β-CD). No significant drug losswas observed in solid dispersion batch (as per results of drug content analysis) during storage for 3 months underaccelerated conditions. Further in vivo pharmacodynamics studies of selected batch were carried out by inducingobesity in rats by feeding them with a high-fat diet. Group I (normal control group) received normal chow diet andgroup II, group III, group IV (High fat diet group, optimized formulation group and disease control group) receivedHFD for 1 month and were further evaluated for BMI, Blood glucose, lipid profile, liver profile, and histopathologicalexamination. The results so obtained depicted that optimized formulation of Atorvastatin (10 mg/kg, p.o.) showedbetter results in comparison to pure Atorvastatin Calcium (10 mg/kg, p.o.).
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Keywords
Cyclodextrins, solubility, dissolution, histopathology, stability, obesity
Citation
Arora Anureet, Aggarwal Geeta, Singh Thakur Gurjeet, Singh Manjinder, Arora Gitika, Nagpal Manju. Inclusion complexes of atorvastatin calcium–sulfobutyl ether β cyclodextrin with enhanced hypolipidemic activity. Journal of Applied Pharmaceutical Science. 2019 Nov; 2019 Nov: 060-068