Atomistic simulations of aqueous griseofulvin crystals in the presence of individual and multiple additives

Document Type

Article

Publication Date

5-7-2012

Abstract

The production and stabilization of crystalline pharmaceutical suspensions, an area of great importance to the pharmaceutical industry, was investigated through exploration of the ability of surfactants and polymers to affect the growth and stability of poorly water soluble pharmaceutical crystals on a molecular scale using molecular dynamics simulations coupled with anti-solvent crystallizations. Griseofulvin, a model poorly soluble drug, was simulated in an aqueous system containing individual non-ionic surfactant Tween 80, polymer HPMC, polymer Pullulan, and anionic surfactant SDS, as well as binary surfactant-polymer mixtures. To evaluate the stability and growth potential of the crystals, the interfacial binding energies between three elementary faces were calculated and compared, based on which HPMC was determined to be the most effective individual additive of those tested. Additionally, the potential synergism of additives was evaluated by the simulation of binary mixtures containing each of the non-ionic additives with the anionic surfactant SDS at different starting configurations. The combination of HPMC with SDS proved to be the most effective and significantly greater than HPMC when used alone. Simulation results were validated by observing both crystal growth rates, as well as final particle sizes of griseofulvin crystals grown using an antisolvent crystallization in the presence of individual and mixtures of additives, suggesting that the simulation approach may be used as a screening tool for selection of additives. © 2012 Elsevier Ltd.

Identifier

84857012054 (Scopus)

Publication Title

Chemical Engineering Science

External Full Text Location

https://doi.org/10.1016/j.ces.2012.01.008

ISSN

00092509

First Page

218

Last Page

230

Volume

73

Grant

0540855

Fund Ref

National Science Foundation

This document is currently not available here.

Share

COinS