Mechanistic Modeling of Wet Stirred Media Milling for Production of Drug Nanosuspensions
- PDF / 1,991,117 Bytes
- 23 Pages / 595.276 x 790.866 pts Page_size
- 45 Downloads / 166 Views
Review Article Theme: Modeling and Simulations of Drug Product Manufacturing Unit Operations Guest Editors: Alexander Russell and Maxx Capece
Mechanistic Modeling of Wet Stirred Media Milling for Production of Drug Nanosuspensions E. Bilgili1,2 and G. Guner1
Received 18 August 2020; accepted 5 November 2020 Abstract.
Drug nanocrystals have been used for a wide range of drug delivery platforms in the pharmaceutical industry, especially for bioavailability enhancement of poorly watersoluble drugs. Wet stirred media milling (WSMM) is the most widely used process for producing dense, stable suspensions of drug nanoparticles, also referred to as nanosuspensions. Despite a plethora of review papers on the production and applications of drug nanosuspensions, modeling of WSMM has not been thoroughly covered in any review paper before. The aim of this review paper is to briefly expose the pharmaceutical scientists and engineers to various modeling approaches, mostly mechanistic, including computational fluid dynamics (CFD), discrete element method (DEM), population balance modeling (PBM), coupled methods, the stress intensity–number model (SI–SN model), and the microhydrodynamic (MHD) model with a main focus on the MHD model for studying the WSMM process. A total of 71 studies, 30 on drugs and 41 on other materials, were reviewed. Analysis of the pharmaceutics literature reveals that WSMM modeling is largely based on empirical, statistically based modeling approaches, and mechanistic modeling could help pharmaceutical engineers develop a fundamental process understanding. After a review of the salient features and various pros–cons of each modeling approach, recent advances in microhydrodynamic modeling and process insights gained therefrom were highlighted. The SI–SN and MHD models were analyzed and critiqued objectively. Finally, the review points out potential research directions such as more mechanistic and accurate CFD–DEM–PBM simulations and the coupling of the MHD–PBM models with the CFD.
KEY WORDS: drug nanoparticles; wet stirred media milling; modeling; microhydrodynamics; process development.
Guest Editors: Alexander Russell and Maxx Capece 1
Otto H. York Department of Chemical and Materials Engineering, New Jersey Institute of Technology, 161 Warren St. 150 Tiernan Hall, Newark, New Jersey, USA. 2 To whom correspondence should be addressed. (e–mail: [email protected]) Nomenclature Symbols a, Average frequency of drug particle compressions, Hz; b,
Breakage distribution parameter,−; B, Cumulative breakage distribution parameter,−; c, Volumetric fraction of the beads, shortly referred to as the bead loading,−; CFD, Computational fluid dynamics; d, Particle diameter (size), m; DEM, Discrete element method; E,Collision (impact) energy, J; Em, Specific impact energy, J/kg; Emin, Emax, Minimum and maximum collision energy, J; ERTD, Residence time distribution function, 1/s; EE, Eulerian–Eulerian; EL, Eulerian– Lagrangian; fcoll, Frequency of particles’ collisions with particles-beads-mill wall, Hz; fMat, Material stre
Data Loading...
