28.06.10 1 Lecture at VUT 1 PAT solution to the drug release prediction Semenov Institute of...
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Transcript of 28.06.10 1 Lecture at VUT 1 PAT solution to the drug release prediction Semenov Institute of...
28.06.10 1Lecture at VUT 1
PAT solution to the drug PAT solution to the drug release predictionrelease prediction
Semenov Institute of
Chemical PhysicsRussian
chemometricsociety
A.L. Pomerantsev,
O.Ye. Rodionova
28.06.10 2Lecture at VUT 2
Generic PAT SolutionsGeneric PAT Solutions
Incoming inspection
Outcoming inspection
Processcontrol
Substance Process Product
28.06.10 3Lecture at VUT 3
Stage Stage 2:2: Process control Process control
Goal: granulation monitoring
Control: In-line
Equipment: J&M
Method: NIR + PLS
Design: Russia + Germany
Implementation: in progress
28.06.10 4Lecture at VUT 4
Objects: PelletsObjects: PelletsSugar +API
Coating: Acryl EZE
28.06.10 5Lecture at VUT 5
ExperimentExperiment
t = 0t = 30t = 42t = 50
NIR Spectra Dissolution Profiles
t = 105
28.06.10 6Lecture at VUT
Data overviewData overviewSamples
1 2 3 4 5 6 7 8 9
B a
t c h
13 25 44 62 82 99 117 136 154 171
14 22 37 52 67 81 98 110 124 142
15 18 30 41 52 62 73 85 97 114
16 19 36 52 67 83 98 114 129 137
17 17 28 38 50 55 64
18 18 31 42 51 61 70 79 89 105
19 39 70 98 127 156 188 215 246 260
20 21 40 59 77 96 115 133 152 168
21 20 30 43 55 67 82 92 105 121
22 24 46 70 89 111 133 155 176 191
23 26 50 74 98 122 150 171 194 209
24 18 31 42 52 63 73 83 94 110
25 19 34 49 64 79 94 109 124 140
26 19 34 48 64 79 95 111 125 140
Process time, min
28.06.10 7Lecture at VUT 7
PAT problemPAT problem
Prediction
28.06.10 8Lecture at VUT 8
DataData
NIR Spectra Dissolution Data
28.06.10 9Lecture at VUT
Evident approachEvident approachSpectra Dissolution time (min)
Wavelengths 0 15 30 45 60 90 120 180 240
Sa
mp
les
1
2
3
4
5
6
7
8
9
X YPLS2
28.06.10 10Lecture at VUT
PLS2 resultsPLS2 results
28.06.10 11Lecture at VUT
Kinetic approachKinetic approachk1 k2 ... kp
Sa
mp
les
1 3.56 0.10 ... 0.33
2 4.03 0.09 ... 0.66
3 4.99 0.10 ... 0.98
4 6.13 0.15 ... 1.28
5 6.84 0.20 ... 1.62
6 7.81 0.25 ... 1.93
7 8.66 0.30 ... 2.23
8 9.49 0.33 ... 2.54
9 9.82 0.35 ... 2.54
Features extraction Y
28.06.10 12Lecture at VUT
AutocatalysisAutocatalysis
100)(;0)0(;1001
21
DDk
kDDk
dt
dD
28.06.10 13Lecture at VUT
Fitter softwareFitter software
28.06.10 14Lecture at VUT
Kinetics of dissolutionKinetics of dissolution
28.06.10 15Lecture at VUT
Parameter Parameter kk11 is common within a batch is common within a batch
28.06.10 16Lecture at VUT 16
Constant Constant kk1 1 and the layer gradeand the layer grade
28.06.10 17Lecture at VUT
Constant Constant kk22 and the layer thickness and the layer thickness
Layer thickness
28.06.10 18Lecture at VUT
A small wonder of scienceA small wonder of science
kinetic parameter k2 in the model
follows the layer thickness
kinetic parameter k2 in the model
follows the layer thickness
kinetic parameter k1 in the model
reflects the material grade
kinetic parameter k1 in the model
reflects the material grade
28.06.10 19Lecture at VUT 19
Prediction of Prediction of kk22: NIR – PLS (White : NIR – PLS (White subset)subset)
28.06.10 20Lecture at VUT 20
Prediction of Prediction of kk22: NIR – PLS (Yellow : NIR – PLS (Yellow subset)subset)
28.06.10 21Lecture at VUT
Prediction techniquePrediction technique
NLRk1 :common for the grade
k21 , .... , k29 : for batch 20
k21 , .... , k29 : for batch 21
k21 , .... , k29 : for batch 22
k21 , .... , k29 : for batch 23
PL
S
PLSk2
28.06.10 22Lecture at VUT 22
Prediction qualityPrediction quality
28.06.10 23Lecture at VUT 23
ConclusionsConclusions
• We’ve obtained a very practical method of prediction
• There is something behind the autocatalytic model
• A lot of hidden information still could be dug up
• We’ve obtained a very practical method of prediction
• There is something behind the autocatalytic model
• A lot of hidden information still could be dug up
28.06.10 24Lecture at VUT
AcknowledgementsAcknowledgements
• GEA Pharma Systems AG, Bubendorf, Switzerland
• Michael Melichar and Anthony Wigmore for data acquisition
• Project PANOPOD-II sponsor Deutsche Bundesstiftung Umwelt (DBU)
• GEA Pharma Systems AG, Bubendorf, Switzerland
• Michael Melichar and Anthony Wigmore for data acquisition
• Project PANOPOD-II sponsor Deutsche Bundesstiftung Umwelt (DBU)