Synthesis and evaluation of ampicillin-conjugated gum arabic microspheres for sustained release.
Ampicillin was conjugated to periodate-oxidized gum arabic (GA), a branched polysaccharide, to form the imino conjugate of the drug and the polysaccharide. The water-soluble conjugate was dispersed by sonication in a mixture of toluene and liquid paraffin in the presence of a non-ionic surfactant as droplet stabilizer and fabricated into microspheres by heat denaturation at 80 degrees C to obtain spheres less than 2 microm in diameter. These microspheres did not undergo dissolution in water on prolonged incubation. In-vitro release of ampicillin into phosphate buffer from the microspheres was slow and sustained with a cumulative release between 10 and 25% of the drug content in 10 days depending on the degree of oxidation of GA and the drug payload. Release into simulated gastric fluid was faster due to faster hydrolysis of the drug-GA bond in the acid medium, but when the medium was changed to intestinal fluid, the release was slowed down. Ampicillin released was functionally active and inhibited the growth of S. aureus and E. coli in cultures, although not as actively as free ampicillin. The microspheres underwent slow biodegradation on prolonged incubation in aqueous media. These studies show that ampicillin conjugated with oxidized GA and fabricated into microspheres possesses sustained-release characteristics for prolonged periods.
Nishi
K K
KK
Division of Polymer Chemistry, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Satelmond Palace Campus, Trivandrum, Kerala 695 012, India.
Antony
M
M
Jayakrishnan
A
A
D000667:Ampicillin / Q000008:administration & dosage / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D005750:Gastric Juice; D006170:Gum Arabic / Q000737:chemistry*; D006868:Hydrolysis; D007419:Intestinal Secretions; D008826:Microbial Sensitivity Tests; D008863:Microspheres; D008899:Mineral Oil; D010084:Oxidation-Reduction; D010316:Particle Size; D010504:Periodic Acid; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013501:Surface-Active Agents; D014050:Toluene
D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D013501:Surface-Active Agents; D010504:Periodic Acid; D014050:Toluene; D000667:Ampicillin; D008899:Mineral Oil; D006170:Gum Arabic; C009288:metaperiodate