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

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Abstract
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 (R) 974P NF (96 : 4) was faster compared to the cospray-dried mixtures of starch with Carbopol (R) 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.
Keywords
MANAGEMENT, RESISTANCE, ABSORPTION, DELIVERY, DRUGS, VIVO EVALUATION, MUCOSAL IRRITATION, OCULAR MINITABLETS, MICROBIAL KERATITIS, STREPTOCOCCUS-FAECALIS, vancomycin, radiostability, ocular minitablet, irritation study, EPR, gentamicin

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Citation

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Chicago
Bozdag, S, W Weyenberg, Els Adriaens, MMM Dhondt, V Vergote, Chris Vervaet, Kristof De Prijck, et al. 2010. “In Vitro Evaluation of Gentamicin- and Vancomycin-containing Minitablets as a Replacement for Fortified Eye Drops.” Drug Development and Industrial Pharmacy 36 (11): 1259–1270.
APA
Bozdag, S., Weyenberg, W., Adriaens, E., Dhondt, M., Vergote, V., Vervaet, C., De Prijck, K., et al. (2010). In vitro evaluation of gentamicin- and vancomycin-containing minitablets as a replacement for fortified eye drops. DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 36(11), 1259–1270.
Vancouver
1.
Bozdag S, Weyenberg W, Adriaens E, Dhondt M, Vergote V, Vervaet C, et al. In vitro evaluation of gentamicin- and vancomycin-containing minitablets as a replacement for fortified eye drops. DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY. 2010;36(11):1259–70.
MLA
Bozdag, S, W Weyenberg, Els Adriaens, et al. “In Vitro Evaluation of Gentamicin- and Vancomycin-containing Minitablets as a Replacement for Fortified Eye Drops.” DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY 36.11 (2010): 1259–1270. Print.
@article{1899268,
  abstract     = {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 (R) 974P NF (96 : 4) was faster compared to the cospray-dried mixtures of starch with Carbopol (R) 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.},
  author       = {Bozdag, S and Weyenberg, W and Adriaens, Els and Dhondt, MMM and Vergote, V and Vervaet, Chris and De Prijck, Kristof and Nelis, Hans and De Spiegeleer, Bart and Ludwig, A and Remon, Jean Paul and nelis, hans},
  issn         = {0363-9045},
  journal      = {DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY},
  keyword      = {MANAGEMENT,RESISTANCE,ABSORPTION,DELIVERY,DRUGS,VIVO EVALUATION,MUCOSAL IRRITATION,OCULAR MINITABLETS,MICROBIAL KERATITIS,STREPTOCOCCUS-FAECALIS,vancomycin,radiostability,ocular minitablet,irritation study,EPR,gentamicin},
  language     = {eng},
  number       = {11},
  pages        = {1259--1270},
  title        = {In vitro evaluation of gentamicin- and vancomycin-containing minitablets as a replacement for fortified eye drops},
  url          = {http://dx.doi.org/10.3109/03639041003718030},
  volume       = {36},
  year         = {2010},
}

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