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S. R. Erickson, C. Hagemeier, J. Missling, T. Klaiber, C. Monasco, S. Fuller; Characterization of Explanted I-vationTM TA Intravitreal Implants from a Phase I Clinical Trial. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5995.
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Sustained-release of triamcinolone acetonide from the I-vationTM sustained drug delivery system has demonstrated a clinical effect in reducing retinal thickness in DME patients in a Phase I clinical trial. Explanted drug delivery systems from this study analyzed for residual drug have allowed the determination of cumulative drug released over time. The data has been compared to in-vitro release of drug into PBS and to that obtained in a rabbit model. The explants were additionally characterized for drug purity, coating appearance and mechanical integrity.
41 I-vationTM TA implants recovered at various time points from 154 to 1082 days in a Phase I clinical trial were analyzed for drug content and purity by HPLC. Coating integrity was assessed by optical microscopy. In-vitro elution was performed in PBS at 37°C under sink conditions. Rabbit data was derived from HPLC analysis of explanted devices at 1,3,6 and 9 month time points.
Data from the Phase I clinical trial demonstrated approximately a two fold higher cumulative release rate over in-vitro elution into PBS. Release rates in the rabbit model correlated well with those of the clinical explants. Triamcinolone acetonide purity in the explant coatings was between 97.4% and 100%. Optical microscopy showed good maintenance of coating integrity.
The I-vationTM TA implants maintained excellent drug purity and polymer coating integrity over their in-life use. Correlations of in-vitro to in-vivo release rates for sustained release systems can be quite variable. The determination of an in-vitro to in-vivo correlation is therefore important for product development. For I-vationTM TA, the in-vitro release rate was seen to be approximately half the rate in the human diseased eye. The use of animal modeling can provide an early correlation for targeting drug release parameters during the formulation phase for this drug delivery platform.
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