Molecular Dynamic Simulations of Ocular Tablet Dissolution

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• 作者：Qian Ru ; Hala M. Fadda ; Chung Li ; Daniel Paul ; Peng T. Khaw ; Steve Brocchini ; Mire Zloh
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2013
• 出版时间：November 25, 2013
• 年：2013
• 卷：53
• 期：11
• 页码：3000-3008
• 全文大小：399K
• 年卷期：v.53,no.11(November 25, 2013)
• ISSN：1549-960X

文摘

Small tablets for implantation into the subconjunctival space in the eye are being developed to inhibit scarring after glaucoma filtration surgery (GFS). There is a need to evaluate drug dissolution at the molecular level to determine how the chemical structure of the active may correlate with dissolution in the nonsink conditions of the conjunctival space. We conducted molecular dynamics simulations to study the dissolution process of tablets derived from two drugs that can inhibit fibrosis after GFS, 5-fluorouracil (5-FU) and the matrix metalloprotease inhibitor (MMPi), ilomastat. The dissolution was simulated in the presence of simple point charge (SPC) water molecules, and the liquid turnover of the aqueous humor in the subconjunctival space was simulated by removal of the dissolved drug molecules at regular intervals and replacement by new water molecules. At the end of the simulation, the total molecular solvent accessible surface area of 5-FU tablets increased by 60 times more than that of ilomastat as a result of tablet swelling and release of molecules into solution. The tablet dissolution pattern shown in our molecular dynamic simulations tends to correlate with experimental release profiles. This work indicates that a series of molecular dynamic simulations can be used to predict the influence of the molecular properties of a drug on its dissolution profile and could be useful during preformulation where sufficient amounts of the drug are not always available to perform dissolution studies.