PMID- 27548263
OWN - NLM
STAT- MEDLINE
DCOM- 20170727
LR  - 20190212
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 8
DP  - 2016
TI  - Design of Experiments to Study the Impact of Process Parameters on Droplet Size 
      and Development of Non-Invasive Imaging Techniques in Tablet Coating.
PG  - e0157267
LID - 10.1371/journal.pone.0157267 [doi]
LID - e0157267
AB  - 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 (XmuCT) 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 mum) 
      and large (70 mum) 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 XmuCT imaging. Addition of commonly used contrast 
      materials to the coating solution improved visualisation of the coating by XmuCT, 
      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.
FAU - Dennison, Thomas J
AU  - Dennison TJ
AD  - Aston School of Pharmacy, Aston University, Birmingham, United Kingdom.
FAU - Smith, Julian
AU  - Smith J
AD  - Viridian Pharma Ltd, Newport, United Kingdom.
FAU - Hofmann, Michael P
AU  - Hofmann MP
AD  - Biomaterials Unit, School of Dentistry, University of Birmingham, Birmingham, 
      United Kingdom.
FAU - Bland, Charlotte E
AU  - Bland CE
AD  - Aston Research Centre for Healthy Ageing, Aston University, Birmingham, United 
      Kingdom.
FAU - Badhan, Raj K
AU  - Badhan RK
AD  - Aston School of Pharmacy, Aston University, Birmingham, United Kingdom.
FAU - Al-Khattawi, Ali
AU  - Al-Khattawi A
AD  - Aston School of Pharmacy, Aston University, Birmingham, United Kingdom.
FAU - Mohammed, Afzal R
AU  - Mohammed AR
AD  - Aston School of Pharmacy, Aston University, Birmingham, United Kingdom.
LA  - eng
PT  - Journal Article
DEP - 20160822
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Coated Materials, Biocompatible)
RN  - 0 (Solutions)
RN  - 0 (Tablets)
SB  - IM
MH  - Coated Materials, Biocompatible/*chemistry
MH  - Drug Compounding/instrumentation/*methods
MH  - Factor Analysis, Statistical
MH  - Microscopy, Confocal
MH  - Nebulizers and Vaporizers
MH  - *Research Design
MH  - Solutions
MH  - Tablets/*chemistry
MH  - Wettability
MH  - X-Ray Microtomography
PMC - PMC4993380
COIS- The authors have the following interests: Financial support was provided by a 
      joint funded MRC CASE award (Grant No. MR/J01236X/1) with Viridian Pharma Ltd. 
      Author Julian Smith is employed by Viridian Pharma Ltd. Malvern Instruments 
      provided equipment and expertise for this study. There are no patents, products 
      in development or marketed products to declare. This does not alter the authors' 
      adherence to all the PLOS ONE policies on sharing data and materials.
EDAT- 2016/08/23 06:00
MHDA- 2017/07/28 06:00
PMCR- 2016/08/22
CRDT- 2016/08/23 06:00
PHST- 2015/11/11 00:00 [received]
PHST- 2016/04/28 00:00 [accepted]
PHST- 2016/08/23 06:00 [entrez]
PHST- 2016/08/23 06:00 [pubmed]
PHST- 2017/07/28 06:00 [medline]
PHST- 2016/08/22 00:00 [pmc-release]
AID - PONE-D-15-49319 [pii]
AID - 10.1371/journal.pone.0157267 [doi]
PST - epublish
SO  - PLoS One. 2016 Aug 22;11(8):e0157267. doi: 10.1371/journal.pone.0157267. 
      eCollection 2016.