title: Fundamental mechanisms for tablet dissolution: simulation of particle deaggregation via Brownian dynamics.
abstract: For disintegrating tablet formulations, deaggregation of small particles is sometimes one of the rate-limiting processes for drug release. Because the tablets contain particles that are in the colloidal size range, it may be assumed that the deaggregation process, at least qualitatively, is governed by Brownian motion and electrostatic and van der Waals interactions, where the latter two can be described by a Derjaguin-Landau-Verwey-Overbeek interaction potential. On the basis of this hypothesis, the present work investigates the applicability of Brownian dynamics (BD) simulations as a tool to understand the deaggregation mechanism on a fundamental level. BD simulations are therefore carried out to determine important deaggregation characteristics such as the so-called mean first passage time (MFPT) and first passage time distribution (FPTD) for various two-, three-, and four-particle aggregates. The BD algorithm is first validated and tuned by comparison with analytical expressions for the MFPT and FPTD in the two-particle case. It is then shown that the same algorithm can also be used for the three-particle case. Lastly, the simulations of three- and four-particle aggregates show that the initial shape of the aggregates may significantly affect the deaggregation time.
authors.affiliation: Department of Chemical Engineering, Chalmers University of Technology, Gothenburg SE-412 96, Sweden. erik.kaunisto@chalmers.se
authors.forename: Erik
authors.initials: E
authors.lastname: Kaunisto
authors.forename: Anders
authors.initials: A
authors.lastname: Rasmuson
authors.forename: Johan
authors.initials: J
authors.lastname: Bergenholtz
authors.forename: Johan
authors.initials: J
authors.lastname: Remmelgas
authors.forename: Lennart
authors.initials: L
authors.lastname: Lindfors
authors.forename: Staffan
authors.initials: S
authors.lastname: Folestad
mesh_terms: D000465:Algorithms; D003102:Colloids / Q000737:chemistry*; D003198:Computer Simulation; D008956:Models, Chemical; D010316:Particle Size; D012995:Solubility; D013607:Tablets / Q000737:chemistry*
chemical_list: D003102:Colloids; D013607:Tablets