Examination of self-crosslinked gelatin as a hydrogel for controlled release.
A gelatin matrix crosslinked by extensive dehydration was examined for use in controlled drug delivery in this preliminary investigation. Crosslinking is necessary to prevent gelatin dissolution and immediate drug release at body temperature. Treatment at 105 degrees C and reduced pressure induced crosslinking in discs prepared from Type B gelatin. Crosslinking was evaluated by determining changes in gelatin solubility at 37 degrees C in a USP paddle dissolution apparatus. The crosslinking treatment was reproducible and resulted in 90% of the original gelatin mass remaining after 12 h in water and in phosphate buffer solutions of pH 3 and 6.4. The treated gelatin discs remained intact for greater than 24 h at pH 6.4. Chlorpromazine.HCl (CPZ) was incorporated as a model drug by soaking the treated gelatin discs in an aqueous solution of the drug. Release of CPZ at 37 degrees C in the dissolution apparatus was fitted to an empirical equation. A coefficient of this equation was used as the initial release rate for comparison between different release profiles. The roles of drug solubility, matrix swelling and erosion, and potential drug-matrix interactions were examined by conducting release studies at pH values of 3, 4, 6.4, and 7.4. The insoluble, un-ionized form of the drug had the slowest release rate. The soluble, ionized form under conditions of maximum swelling and a possible drug-matrix repulsive interaction had the fastest release rate. General electrostatic drug-matrix interactions were noted which could influence the drug release rate depending on conditions of the study. The times for 50% release of CPZ ranged from 1.8 to 11.3 h.
Welz
M M
MM
Philadelphia College of Pharmacy and Science, Department of Pharmaceutics, PA 19104.
Ofner
C M
CM
D002746:Chlorpromazine / Q000737:chemistry / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D003890:Desiccation; D005780:Gelatin / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D012995:Solubility
D003692:Delayed-Action Preparations; D005780:Gelatin; D002746:Chlorpromazine