Molecular dynamic simulations of ocular tablet dissolution

Qian Ru, Hala Fadda, Chung Li, Daniel Paull, Sir Peng Khaw, Stephen Brocchini, Mire Zloh

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Small tablets for implantation into the sub-conjunctival 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 chemical structure of the active may correlate with dissolution in the non-sink 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 dynamics 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.
Original languageEnglish
Pages (from-to)3000-3008
JournalJournal of Chemical Information and Modeling
Issue number11
Early online date27 Sept 2013
Publication statusPublished - Nov 2013


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