Alginate-based in situ gelling suspensions and emulsions comprising N4-alkyloxycarbonyl derivatives of cytosine: zero-order release and effect of physicochemical properties.
As an alternative to incorporation of various excipients, N(4)-alkyloxycarbonyl-cytosine derivatives possessing various physicochemical properties and cytosine regeneration rates have been examined to modify release rate and kinetics from in situ gelling alginate formulations, e.g., liquid formulations that gel in acidic gastric juice and release the entrapped derivative or parent cytosine. Linear relationships were obtained between the release rate constants and the square root of the solubility for suspension formulations. Calculated diffusion coefficients were observed to be similar for suspension and solution formulations; however, for in situ gelling emulsion formulations, diffusivity correlated linearly to log P. Zero-order release of parent cytosine was observed from in situ gelling suspensions of the poorly soluble acid-labile N(4)-adamantyloxycarbonyl-cytosine prodrug.
Petersson
Karsten
K
Department of Pharmaceutics, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark. petersson@leo-pharma.com
Larsen
Claus
C
D000081:Acetamides / Q000737:chemistry; D000464:Alginates / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004655:Emulsions; D005782:Gels; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D012996:Solutions; D013535:Suspensions
D000081:Acetamides; D000464:Alginates; D003692:Delayed-Action Preparations; D004655:Emulsions; D005782:Gels; D006603:Hexuronic Acids; D012996:Solutions; D013535:Suspensions; D020723:Glucuronic Acid; D003596:Cytosine; C013959:dimethylacetamide