Drug release from hydroethanolic gels. Effect of drug's lipophilicity (logP), polymer-drug interactions and solvent lipophilicity.
We demonstrate drug release properties from hydroethanolic formulations as a function of the drug's lipophilicity (logP), 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 (logP=2.6) and the burst (Fickian) release of hydrophilic drug, lidocaine hydrochloride (logP<or=0). Thus, logP 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 (approximately 50%) topically than other hydrophobic polymers: Eudragit S100 (anionic) and Eudragit RLPO (cationic copolymer with quaternary ammonium group) ( approximately 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 HPC 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.
Sawant
Prashant D
PD
Stiefel - a GSK Company, 8 Macro Court, Rowville, Victoria 3178, Australia. prashant.sawant@stiefel.com
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D000179:Acrylates / Q000737:chemistry; D000779:Anesthetics, Local / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D000431:Ethanol / Q000737:chemistry*; D005233:Fatty Alcohols / Q000737:chemistry*; D005782:Gels; D007700:Kinetics; D008012:Lidocaine / Q000737:chemistry*; D008956:Models, Chemical; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods
D000179:Acrylates; D000779:Anesthetics, Local; D004337:Drug Carriers; C477020:Eudragit E100; D005233:Fatty Alcohols; D005782:Gels; D011108:Polymers; D011109:Polymethacrylic Acids; D012997:Solvents; C038300:methylmethacrylate-methacrylic acid copolymer; D000431:Ethanol; D002482:Cellulose; D008012:Lidocaine; C008079:hydroxypropylcellulose; C026199:isostearyl alcohol