A three-dimensional anisotropic point process characterization for pharmaceutical coatings

Abstract

Spatial characterization and modeling of the structure of a material may provide valuable knowledge on its properties and function. Especially, for a drug formulation coated with a polymer film, understanding the relationship between pore structure and drug release properties is important to optimize the coating film design. Here, we use methods from image analysis and spatial statistics to characterize and model the pore structure in pharmaceutical coatings. More precisely, we use and develop point process theory to characterize the branching structure of a polymer blended film with data from confocal laser scanning microscopy. Point patterns, extracted by identifying branching points of pore channels, are both inhomogeneous and anisotropic. Therefore, we introduce a directional version of the inhomogeneous K-function to study the anisotropy and then suggest two alternative ways to model the anisotropic * Corresponding author Email address: henrike.habel@chalmers.se (Henrike Häbel)Preprint submitted to Spatial Statistics October 10, 2017 three-dimensional branching point structure. First, we apply a linear transformation to the data such that it appears isotropic and subsequently fit isotropic inhomogeneous Strauss or Lennard-Jones models to the transformed pattern.Second, we include the anisotropy directly in a Lennard-Jones and a more flexible step-function model with anisotropic pair-potential functions. The methods presented here will be useful for anisotropic inhomogeneous point patterns in general and for characterizing pharmaceutical coatings or other porous material in particular.

Prediction of diffusive transport through polymer films from characteristics of the pore geometry

“…The parametric family of stochastic models developed in Barman and Bolin was used to generate samples of pore structures. The family is aimed at modeling pore structures in ethylcellulose/hydroxypropylcellulose (EC/HPC) films from Häbel et al Using estimated covariance functions; a number of geometric goodness of fit measures; and comparing numerically simulated diffusion in the films with diffusion in simulated samples from the model, this family was in Barman and Bolin shown to give good fit to 3D confocal laser scanning microscopy (CLSM) images of two EC/HPC free films, one with 30% HPC and the other with 40% HPC.…”

Characterisation of pore structures of pharmaceutical tablets: A review

“…There are also several techniques utilising electromagnetic radiation that are sensitive to the volume of the pores. These methods include focused ion beam SEM (FIB-SEM) (Heng et al, 2007;Moghadam et al, 2006;Palmas et al, 2016;Poozesh et al, 2017), confocal laser scanning microscopy (CLSM) ( Barman and Bolin, 2017;Häbel et al, 2017;Marucci et al, 2013), nuclear magnetic resonance (NMR, see section 5), Xray computed microtomography (XµCT, see section 6), and terahertz time-domain spectroscopy (THz-TDS, see section 7). NMR is also a void-space sensitive method as it utilises the interaction of the liquid in the pores and solid phase to reveal structural properties of the porous medium.…”

A three‐dimensional statistical model for imaged microstructures of porous polymer films

“…More details about the preparation and imaging of these films can be found in Häbel et al . (). The EC/HPC material has previously been studied experimentally in Marucci et al .…”

“…() and characterized statistically in Häbel et al . (, ). The mass transport properties of the material have been investigated using numerically calculated diffusion in Gebäck et al .…”

“…More details about the preparation and imaging of these films can be found in Häbel et al (2017). The EC/HPC material has previously been studied experimentally in Marucci et al (2009Marucci et al ( , 2013; Andersson et al (2013) and characterized statistically in Häbel et al (2016Häbel et al ( , 2017. The mass transport properties of the material have been investigated using numerically calculated diffusion in Gebäck et al (2015).…”