Design of Experiments to Study the Impact of Process Parameters on Droplet Size and Development of Non-Invasive Imaging Techniques in Tablet Coating

PLoS One. 2016 Aug 22;11(8):e0157267. doi: 10.1371/journal.pone.0157267. eCollection 2016.

Abstract

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats.

MeSH terms

  • Coated Materials, Biocompatible / chemistry*
  • Drug Compounding / instrumentation
  • Drug Compounding / methods*
  • Factor Analysis, Statistical
  • Microscopy, Confocal
  • Nebulizers and Vaporizers
  • Research Design*
  • Solutions
  • Tablets / chemistry*
  • Wettability
  • X-Ray Microtomography

Substances

  • Coated Materials, Biocompatible
  • Solutions
  • Tablets

Grants and funding

Financial support was provided by a joint funded MRC CASE award (Grant No. MR/J01236X/1) with Viridian Pharma Ltd. The kind use of equipment and expertise provided by Malvern Instruments and Michelle Holder of the University of Birmingham School of Dentistry is very much appreciated. Malvern Instruments had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author Julian Smith is employed by Viridian Pharma Ltd. Viridian Pharma Ltd provided support in the form of salary for author JS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.