In vitro evaluation of gentamicin- and vancomycin-containing minitablets as a replacement for fortified eye drops

• Published in: Drug development and industrial pharmacy Vol. 36; no. 11; pp. 1259 - 1270
• Main Authors: Bozdag, S., Weyenberg, W., Adriaens, E., Dhondt, M.M.M., Vergote, V., Vervaet, C., De Prijck, K., Nelis, H.J., De Spiegeleer, B., Ludwig, A., Remon, J.P.
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.11.2010; Taylor & Francis
• Subjects: Acrylic Resins; Adhesiveness; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - toxicity; Drug Stability; Drug Storage; EPR; Excipients - chemistry; Gastropoda; gentamicin; Gentamicins - administration & dosage; Gentamicins - pharmacology; Gentamicins - toxicity; Humans; irritation study; Mucous Membrane - drug effects; ocular minitablet; Polyvinyls - chemistry; radiostability; Staphylococcus epidermidis - drug effects; Starch - chemistry; Tablets; Toxicity Tests; vancomycin; Vancomycin - administration & dosage; Vancomycin - pharmacology; Vancomycin - toxicity
• ISSN: 0363-9045; 1520-5762
• DOI: 10.3109/03639041003718030

Objective: Ocular bioadhesive minitablets containing gentamicin and vancomycin were developed using different powder mixtures of pregelatinized starch and Carbopol (physical or cospray-dried mixtures). Methods: Drug content, antimicrobial activity, and radical formation of the powders used for tablet preparation were evaluated immediately and 30 days after gamma sterilization. Tablet properties and in vitro drug release from the sterilized minitablets were determined. Storage stability of vancomycin and gentamicin in sterilized bioadhesive mixtures was examined by LC-UV MS and a microbiological assay, respectively. A bioadhesive powder mixture containing only vancomycin was irradiated by X electron-magnetic radiation to evaluate vancomycin stability following sterilization through irradiation. Results: The antimicrobial activity of gentamicin against Staphylococcus epidermidis was not altered in comparison to nonsterilized formulations. Only after an overkill dose of 50 kGy, the concentration of vancomycin decreases to an extent that was pharmaceutically significant. No significant difference in radiation stability between drug substance and product (i.e., powder mixture) was observed. A shift in stability profile was not observed at 6 weeks after irradiation. All other degradation products were present only in small quantities not exceeding 1.0%. The in vitro drug release from the minitablets prepared with physical powder mixtures of pregelatinized starch and Carbopol® 974P NF (96 : 4) was faster compared to the cospray-dried mixtures of starch with Carbopol® 974P NF (ratio: 95:5 and 85:15). The electron paramagnetic resonance signals of the radicals formed during sterilization were still visible after storage for 30 days. The slug mucosal irritation test indicated mild irritation properties of the bioadhesive powder mixtures although no tissue damage was observed.