From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Tue, May 13, 2008 at 11:17 PM
Subject: Effect of formulation parameters on 2-methoxyestradiol release from injectable cylindrical poly(dl-lactide-co-glycolide) implants.
To: mesothelioma77@gmail.com
[1]Eur J Pharm Biopharm. 2008 Mar 20;
Desai KG, Mallery SR, Schwendeman SP
The objective of this study was to investigate the potential of various formulation strategies to achieve 1-month continuous (improved) release of the novel anti-cancer drug, 2-methoxyestradiol (2-ME), from injectable cylindrical poly(dl-lactide-co-glycolide) (PLGA) implants. PLGA implants were prepared by a solvent extrusion method. PLGA 50:50 (M(w)=51kDa, end group=lauryl ester) (PLGA-lauryl ester) implants loaded with 3-30wt% 2-ME exhibited a pronounced lag phase (i.e., corresponding to induction time to polymer mass loss) and triphasic release profile. Incorporation of 5wt% hydroxypropyl-beta-cyclodextrin (HP-beta-CD) ( approximately 57% release after 28days) or Pluronic((R)) F127 ( approximately 42% release after 28days) in PLGA-lauryl ester implants reduced the lag-phase and improved the drug release moderately over a period of 28days. The formation and the incorporation of a 2-ME/polyethylene glycol (PEG) 8000 solid dispersion in PLGA-lauryl ester implants further increased drug release ( approximately 21% and 73% release after 1 and 28days, respectively), attributable to improved drug solubility/dissolution, higher matrix porosity, and accelerated polymer degradation. Blending of PLGA 50:50 (M(w)=24kDa, end group=COOH) (PLGA-COOH) with the PLGA-lauryl ester also provided moderate enhancement of 2-ME release over a period of 28days. PLGA-COOH (M(w)=24kDa) implants with 3-5% w/w pore-forming MgCO(3) exhibited the most desirable drug release among all the formulations tested, and, demonstrated 1-month slow and continuous in vitro release of approximately 80% 2-ME after a minimal initial burst. Hence, these formulation approaches provide several possible avenues to improve release rates of the hydrophobic drug, 2-ME, from PLGA for future application in regional anti-cancer therapy.
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Source: http://www.hubmed.org/display.cgi?uids=18472254
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