University of Hertfordshire

Molecular dynamic simulations of ocular tablet dissolution

Research output: Contribution to journalArticle

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Molecular dynamic simulations of ocular tablet dissolution. / Ru, Qian; Fadda, Hala; Li, Chung; Paull, Daniel; Khaw, Sir Peng; Brocchini, Stephen; Zloh, Mire.

In: Journal of Chemical Information and Modeling, Vol. 53, No. 11, 11.2013, p. 3000-3008.

Research output: Contribution to journalArticle

Harvard

Ru, Q, Fadda, H, Li, C, Paull, D, Khaw, SP, Brocchini, S & Zloh, M 2013, 'Molecular dynamic simulations of ocular tablet dissolution', Journal of Chemical Information and Modeling, vol. 53, no. 11, pp. 3000-3008. https://doi.org/10.1021/ci4002348

APA

Vancouver

Author

Ru, Qian ; Fadda, Hala ; Li, Chung ; Paull, Daniel ; Khaw, Sir Peng ; Brocchini, Stephen ; Zloh, Mire. / Molecular dynamic simulations of ocular tablet dissolution. In: Journal of Chemical Information and Modeling. 2013 ; Vol. 53, No. 11. pp. 3000-3008.

Bibtex

@article{ce5a1f16bd3747bca764973483ba8ace,
title = "Molecular dynamic simulations of ocular tablet dissolution",
abstract = "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.",
author = "Qian Ru and Hala Fadda and Chung Li and Daniel Paull and Khaw, {Sir Peng} and Stephen Brocchini and Mire Zloh",
year = "2013",
month = "11",
doi = "10.1021/ci4002348",
language = "English",
volume = "53",
pages = "3000--3008",
journal = "Journal of Chemical Information and Modeling",
issn = "1549-9596",
publisher = "American Chemical Society",
number = "11",

}

RIS

TY - JOUR

T1 - Molecular dynamic simulations of ocular tablet dissolution

AU - Ru, Qian

AU - Fadda, Hala

AU - Li, Chung

AU - Paull, Daniel

AU - Khaw, Sir Peng

AU - Brocchini, Stephen

AU - Zloh, Mire

PY - 2013/11

Y1 - 2013/11

N2 - 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.

AB - 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.

U2 - 10.1021/ci4002348

DO - 10.1021/ci4002348

M3 - Article

VL - 53

SP - 3000

EP - 3008

JO - Journal of Chemical Information and Modeling

JF - Journal of Chemical Information and Modeling

SN - 1549-9596

IS - 11

ER -