Drug release from hydroethanolic gels. Effect of drug's lipophilicity (log P), polymer-drug interactions and solvent lipophilicity

We demonstrate drug release properties from hydroethanolic formulations as a function of the drug's lipophilicity (log P), solvent lipophilicity and drug-polymer interactions, for the first time A hydrophilic polymer, hydroxypropyl cellulose (HPC), provides the non-Fickian slower release of the lipophilic drug, lidocaine (log P = 2 6) and the burst (Fickian) release of hydrophilic drug, lidocaine hydrochloride (log P <= 0). Thus, log P of drugs helps predict the drug release properties. Hydrophobic Eudragit polymers provided the burst release of lidocaine However, the cationic hydrophobic polymer (Eudragit E100) retained more lidocaine (similar to 50%) topically than other hydrophobic polymers Eudragit 5100 (anionic) and Eudragit RLPO (cationic copolymer with quaternary ammonium group) (similar to 25% lidocaine retention) which release lidocaine systematically. Thus, minute changes in functional groups of hydrophobic polymers help tune the lidocaine release topically or systemically. An interaction between H PC and lidocaine as determined by FTIR helps the non-Fickian slower lidocaine release from HPC formulations However, no interactions between lidocaine and hydrophobic Eudragit polymers explain the Fickian burst release of lidocaine from their formulations A lipophilic solvent. isostearyl alcohol which when replacing ethanol by 30%. slows the release rate and enhances the topical adsorption of lidocaine. Thus, solvent lipophilicity also modulates drug release properties. (C) 2010 Elsevier B.V. All rights reserved.