| Lyophilization monophase solution technique for improvement of the physicochemical properties of an anticancer drug, flutamide. | |
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MedLine Citation:
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PMID: 19944160 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Flutamide (FLT), an anticancer drug for prostatic carcinoma, has poor aqueous solubility and low oral bioavailability. This study describes the ability of beta-cyclodextrin (betaCD) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) to form complexes with flutamide with enhanced solubility and dissolution rate in vitro. FLT-CD lyophilized dispersions (LDs) were prepared via lyophilization monophase solution technique using tertiary butyl alcohol (TBA) as a cosolvent. FLT showed an A(L)-type phase solubility diagram consistent with a linear increase in drug solubility as a function of CD concentration. Gas chromatography indicated that the LDs contain 0.02-0.03% w/w residual TBA. Based on the data from differential scanning calorimetry (DSC) and X-ray diffractometry (XRD), FLT was fully amorphous in 1:5 FLT-HPbetaCD LD as indicated by complete disappearance of FLT endothermic and diffraction peaks. The Fourier transform infrared (FTIR) spectra indicated that a FLT-CD interaction took place in the lyophilized complex. The particle sizes of 1:1 FLT-betaCD and FLT-HPbetaCD LDs were 0.92 and 0.82microm, with a high surface area (484.55 and 705.68m(2)/g) and porosity (769.46 and 1020.99e(-3)ml/g), respectively. The dissolution rate of FLT from its CD complexes was enhanced significantly. After 30min in 0.1N HCl, about 73% and 86% of FLT were dissolved from 1:5 FLT-betaCD and FLT-HPbetaCD LDs, respectively, compared to only 13.45% of pure drug. No endothermic peak corresponding to FLT melting was detected in 1:5 FLT-HPbetaCD LD after storage at 20 degrees C and 45% relative humidity for 90days thus indicating the stability of this binary system. These data suggest that cyclodextrins might be useful adjuncts in preparation of immediate-release formulations of FLT. |
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Authors:
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Nazik Elgindy; Kadria Elkhodairy; Abdallah Molokhia; Ahmed Elzoghby |
Publication Detail:
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Type: Journal Article Date: 2009-11-26 |
Journal Detail:
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Title: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft f?r Pharmazeutische Verfahrenstechnik e.V Volume: 74 ISSN: 1873-3441 ISO Abbreviation: Eur J Pharm Biopharm Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-02-15 Completed Date: 2010-05-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9109778 Medline TA: Eur J Pharm Biopharm Country: Netherlands |
Other Details:
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Languages: eng Pagination: 397-405 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2009 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Industrial Pharmacy, University of Alexandria, Alexandria, Egypt. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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chemistry* Crystallization Drug Compounding / methods* Drug Stability Flutamide / chemistry* Freeze Drying / methods* Particle Size Pharmaceutical Solutions / chemistry Solubility Surface Properties beta-Cyclodextrins / chemistry |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Pharmaceutical Solutions; 0/beta-Cyclodextrins; 13311-84-7/Flutamide; 94035-02-6/2-hydroxypropyl-beta-cyclodextrin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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