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Richard C. Coulon, Thomas E. Rowe, Janet M. Akande, Ken Reed, Mario G. Fsadni; Measurement and Prediction of Active Pharmaceutical Ingredient Diffusion With and Without Simulated Tear Flow. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3234.
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© ARVO (1962-2015); The Authors (2016-present)
In vitro comparison of the effect of formulation changes on the diffusion of drug using a dynamic corneal diffusion model. It has been previously shown that a dynamic diffusion model more accurately describes the impact of formulation variations than a more typical static diffusion model (ARVO 2010 program # 2452). Various retention enhancement formulations were studied to determine the optimum release rate of drug from the various drug matrices.
Rabbit corneas were placed on a specially adapted spherical Franz Cells. Samples of various formulations of the API were placed on the cornea. Experiments were performed comparing the new formulations to an aqueous solution formulation. Corneal permeate containing drug in the receiver was collected over time. Samples were also collected through the outlet flow port of the donor compartment representing drug lost through drainage.
There were significant differences in the diffusion characteristics when comparing the diffusion profile of the solution formulation to those of retention enhanced formulations. Enhanced formulations showed improved cross corneal diffusion even though the formulations contained lower concentrations of API. The combination of the lower amount of drug in the formulation along with the retention enhancement of the formulation resulted in severely reduced amounts of drug eliminated by the action of the simulated tear flow.
Cross corneal diffusion profiles are an important parameter in predicting ocular drug disposition. This in vitro model was helpful in quickly identifying formulation alternatives which could be selected based on the preferred drug release profile.
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