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U NUI NV IEVRESRI ST IYT YO FO FC OCPOEPNEHNAHGAEGNE N Department of Pharmacy Faculty of and Medical Medical Sciences Sciences Faculty of Health Helth and Chemical mapping and multivariate image analysis of tablet surface: A comparative study of multispectral UV and hyperspectral NIR imaging Jian Xiong Wu Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen Email: [email protected] Dias 1 ISPE Nordic PAT COP, Malmö, 2013 UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Outline Background • A dream to become true • Multispectral UV imaging for chemical mapping Case study • Monitoring tablets using UV and NIR imaging • Proposing a multivariate image analytical flow for pioneering work • Results Conclusions Dias 2 UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Why bother with CI in pharmaceutical development? API stability? Degradation? API distribution? Dose dumping? Formulation understanding Dias 3 F.Franch-Lage et al., Int. J. Pharm. 2011 Amigo, Anal Bioanal Chem. 2010 Lewis et al., The role of Spectroscopy in Process Analytical Technologies, 2011 Ho et al., European Journal of Pharmaceutics and Biopharmaceutics, 2009 UNIVERSITY OF COPENHAGEN university of copenhagen The principle Amigo, Anal Bioanal Chem. 2010 Time of analysis Dias 4 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Current hyperspectral imaging practice Wu et al., Current Pharmaceutical Design (accepted) Dias 5 UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Current hyperspectral imaging practice • Raman • IR • NIR • Many measured wavelengths (100s-1000s) • Visualization of chemical component • Data acquisition time: min – hour per tablet Dias 6 UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Fast online imaging process monitoring – a dream to become true! Can hypespectral imaging be used as online sensors? We need: •Fast imaging systems •High spatial resolution batch imaging •Efficient scattering •Multivariate image processing •Image analysis •Stream line with PAT 80-90% of all API contains aromatic rings: UV active Dias 7 UNIVERSITY OF COPENHAGEN university of copenhagen Redefining the role of UV ray Dias 8 Boetker et al., Mol. Pharm. 2011 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Multispectral UV imager 254, 280, 300, 313, 334 and 365 nm Dias 9 Wu et al., (manuscript in preparation) UNIVERSITY OF COPENHAGEN university of copenhagen Case study Test tablets containing: -Amorphous glibenclamide (amor. API) -Crystalline glibenclamide (cryst. API) -Microcrystalline cellulose (MCC) -Magnesium stearate (MgSt) Dias 10 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen Case study design Dias 11 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Study Aim Can the UV imaging visualize the API forms? Can the UV imaging distiguish API from excipients? Propose a multivariate image analytical strategy Compare the result with hyperspectral NIR imaging Dias 12 UNIVERSITY OF COPENHAGEN university of copenhagen The raw data Dias 13 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Reference UV absorbance profile Dias 14 UNIVERSITY OF COPENHAGEN university of copenhagen Data analytical strategy Dias 15 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy PCA MCC MgSt The references can be separated Project not failed. Dias 16 Amor. API Cryst. API UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Theory of working principle API in solid state packing API MCC Mgst Dias 17 UNIVERSITY OF COPENHAGEN university of copenhagen Data analytical strategy Dias 18 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen Mixed pixels Amigo, Anal Bioanal Chem. 2010 Dias 19 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Mixed pixels? Amor. API Crys. API MCC MgSt Dias 20 UNIVERSITY OF COPENHAGEN university of copenhagen Mixed pixels? Test tablet Dias 21 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Evolving factor image analysis A. de Juan et al., Chemometrics and Intelligent Laboratory Systems, 2005 (modified) Dias 22 UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Evolving factor image analysis on UV data Dias 23 UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Complexity image 4-5 3 2 1 Dias 24 UNIVERSITY OF COPENHAGEN university of copenhagen Data analytical strategy Dias 25 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Multivariate Curve Resolution Aim: Each UV profile is resolved into its pure underlying chemical profile That is xtest = *xamor API + *xcry API + *xMCC +* xMgst + e Constraint +++ = 1 in matrix notation X = CST + E Dias 26 UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Multivariate Curve Resolution Amor. API Cry. API MCC Dias 27 Mgst UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Visualization of chemical components Amor API MCC Dias 28 Cry API Mgst UNIVERSITY OF university of copenhagen COPENHAGEN Department Department ofof Pharmacy Department ofPharmacy Pharmacy NIR reference Raw spectra Dias 29 2. derivative, mean centered UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Evolving factor image analysis on NIR data Dias 30 UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Complexity image 3 2 1 Dias 31 UNIVERSITY OF university of copenhagen COPENHAGEN MCR on NIR data Ref. spec. MCR calculated spec Dias 32 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen UV vs. NIR image, Amor API Dias 33 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen UV vs. NIR image, Cry. API Dias 34 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen UV vs. NIR image, MCC Dias 35 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen UV vs. NIR image, Mgst Dias 36 Department Department ofof Pharmacy Department ofPharmacy Pharmacy UNIVERSITY OF COPENHAGEN university of copenhagen Department Department ofof Pharmacy Department ofPharmacy Pharmacy Conclusion UV imaging is: -Fast (15 sec in imaging 7 x 7 cm) -Reasonable high spatial resolution (70 µm) -Particular sensitive for API -Distinguish between solid state forms of API and excipients -Distinguishing between excipients is challenging -Has online monitoring potential Multivariate image analysis: -EFA is useful for estimating pixel complexity -Imaging with few wavelengths has its advantage -MCR allows chemical meaningful data decomposition Dias 37 UNIVERSITY OF COPENHAGEN university of copenhagen Acknowledgement DTU / Videometer Jens Michael Carstensen Lundbeck Uffe Teis Svare Morten Allesø Faculty of Science, KU José Manuel Amigo Frans van den Berg Faculty of Health and Medical Sciences, KU Jukka Rantanen Thomas Rades Hamburg University Sönke Rehder Novo Nordisk Erik Skibsted DTI Dias 38 Katherine Bjørneboe Department Department ofof Pharmacy Department ofPharmacy Pharmacy
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