Claude Mazuel

Gelrite®: a novel, ion-activated, in-situ gelling polymer for ophthalmic vehicles. Effect on bioavailability of timolol

Abstract Gelrite® solution, a novel ophthalmic vehicle, gels in the presence of mono or divalent cations. In the conjunctival sac ‘ion-activation’ of the sol/gel transition is accomplished by the lacrimal fluid. A 0.6% Gelrite® vehicle has been compared to an equiviscous solution of hydroxyethylcellulose (HEC) using timolol maleate as a drug probe. In vitro release rates of timolol from HEC and Gelrite® gel were similar. In vivo, the formation of the gel prolonged precorneal residence time and increased ocular bioavailability of timolol in the cornea, aqueous humor and iris + ciliary body of albino rabbits.

Functionality testing of gellan gum, a polymeric excipient material for ophthalmic dosage forms

Low acetyl gellan gum, originally a food ingredient, has been used to devise novel ophthalmic formulations, significantly improving drug ocular bioavailability. This increase in drug bioavailability results from the unique gelling property of gellan gum in the presence of tear fluid cations. The aim of this study was to develop a functionality test ensuring the consistency of the dosage forms gelling property and a reproducible pharmacological effect. The rupture strength of the gel was shown to be a reliable indicator of the ocular drug bioavailability in the albino rabbit. The test parameters susceptible to influence the test results were identified, evaluated and optimized. The influence of the raw material characteristics and of the processing parameters on the final product gel strength were determined and optimized, and finished product specifications established.

HPLC-MS/MS determination of a peptide conjugate prodrug of doxorubicin, and its active metabolites, leucine-doxorubicin and doxorubicin, in dog and rat plasma

A HPLC-MS/MS Electrospray (ESI) method was developed and validated to quantify a peptide conjugate prodrug of doxorubicin (Dox-Con) and its active metabolites leucine-doxorubicin (Leu-Dox) and doxorubicin (Dox) in dog and rat plasma. The analytes were extracted from plasma by solid-phase extraction on a Bond Elut C8 cartridge and eluted with chloroform-methanol (2:1). Eluates were evaporated and reconstituted in acetonitrile-5 microM sodium trifluoroacetate in 0.1% aqueous formic acid (20:80) and injected onto a Waters Oasis HLB column. Analytes were eluted from the column with a solvent gradient into the mass analyzer. The ions were quantified in the selected reaction-monitoring mode (SRM), using positive ions, on a triple quadrupole mass spectrometer. The lower limits of quantification for Dox-Con, Leu-Dox, and Dox in plasma, were approximately 5, 1 (dog)/6 (rat), and 0.5 ng/ml, respectively. Intra- and inter-assay accuracy (% of nominal concentration) and precision (%CV) for all analytes were within 15 and 16%, respectively.