- Growth and shrinking of Pluronic micelles in Pluronic-flurbiprofen solutions: variation of concentration and pH. S Alexander, SW Prescott, T Cosgrove and TC Castle. UK Colloids 2011, July 2011.
Solubility of highly hydrophobic drugs such as flurbiprofen for oral dosage forms has been challenging and different strategies have been applied in order to increase the adsorption and bioavailability of these drugs. Flurbiprofen is a very effective anti-inflammatory drug which is used to treat pain, swelling, and stiffness caused by osteoarthritis and rheumatoid arthritis. Polyethylene-polypropylene-polyethylene tri-block copolymers have shown significant potential as drug carriers, in particular for encapsulation of hydrophobic drugs. Because of the hydrophobic character of PPO blocks, multi-molecular micelles form above the critical micellisation concentration (CMC) and critical micellisation temperature (CMT). In this paper we discuss the use of Pulsed-field gradient stimulated-echo nuclear magnetic resonance (NMR) and surface densitometry to study the effect of drug addition and pH variation on micellisation behavior of Pluronics triblock copolymers (P103, P123, and L43). At various flurbiprofen concentrations, a substantial increase in the hydrodynamic radius of Pluronic P103 from 6nm to 15nm (with the highest drug content) was found by PFGNMR. From these data we can also know that the addition of flurbiprofen increases the aggregation number, fraction of polymer micellised and fraction of drug interacting with the polymer. These data clearly show that nearly all of the flurbiprofen is localized within the polymer micelles as desired for targeting, improved solubilisation and controlled release. The pH triggered behavior of the Pluronic-drug solutions was also studied and a strong pH dependent was observed when raising the pH above the pKa of flurbiprofen. The data showed that above pH 4.5, drug is gradually released from the micelles as a result of its improved solubility, leading to shrink of the micelles and decreased in the polymer micellisation. The size and aggregation number of the micelles, the quantity of the block copolymers and of the flurbiprofen have a great influence of using these Pluronic copolymers in possible application to drug deliveries.
Last edited: Friday September 10, 2010
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