Fundamental mechanisms for tablet dissolution: Simulation of particle deaggregation via brownian dynamics
Artikel i vetenskaplig tidskrift, 2013

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.

mathematical model

algorithm

diffusion

capsules

in silico modeling

drug release

colloid

colloidal particles

dynamic simulation

agglomeration

models

Författare

Erik Kaunisto

Chalmers, Kemi- och bioteknik, Kemisk apparatteknik

Anders Rasmuson

Chalmers, Kemi- och bioteknik, Kemisk apparatteknik

Johan Bergenholtz

Göteborgs universitet

Johan Remmelgas

AstraZeneca AB

Lennart Lindfors

AstraZeneca AB

S. Folestad

AstraZeneca AB

Journal of Pharmaceutical Sciences

0022-3549 (ISSN)

Vol. 102 1569-1577

Ämneskategorier

Farmaceutisk vetenskap

DOI

10.1002/jps.23507