NI NIR R ba base sed d ap approach proach to to eva evalu - PowerPoint PPT Presentation

NI NIR R ba base sed d ap approach proach to to eva evalu luate ate an anhy hydrate drate-hydra hydrate te tr tran ansformat sformations ions Dha hara a Ra Raij ijada, a, Ki Kinja jal l Koradia ia, Mia , Mia La Lars rsen, , Vis isha hal l Koradia ia, , Cla laus us Corn rnett, tt, Juk ukka ka Ra Rantan anen Elect ectronic onic Co Conferen erence ce on Ph Pharmaceutical maceutical Sc Sciences ences ECP CPS2 S2011/F 011/Futu ture re Mnauf ufact cturing uring of Ph Pharmaceu maceutical icals

Outline Ou tline  In Intro roducti duction on  Need for PAT tools in pharmaceutical development  NIR spectroscopy as a PAT tool  So Solid lid fo form rms of s of Na Napr prox oxen en so sodi dium um (N (NS) S)  Ob Object jective ive of of th the pr e pres esen ent t wo work rk  Re Resu sult lts  TGA and PXRD patterns  FTIR and NIR spectra  Scores and loadings plot from NIR spectra  Su Summ mmary ary ECPS 2011/Future Manufacturing of Pharmaceuticals 2

Need eed fo for Pr r Proc ocess ess An Analy alytical tical Te Techn chnol olog ogy y to tool ols “QUALITY PHARMACEUTICAL PRODUCT” Understanding of the solid form during various phases of development : Crucial factor Important to identify suitable technique during early development that can monitor such changes and can be developed as a PAT tool for future manufacturing of pharmaceutical products ECPS 2011/Future Manufacturing of Pharmaceuticals 3

NIR IR Sp Specro ecrosco scopy py as a as a PA PAT to T tool ol  Fast, noninvasive and real time data acquisition possibilities makes NIR as one of the ideal PAT tools  Multivariate data analysis from NIR spectral data can provide simple and quick approach for extracting information from NIR spectral data Katherine A. Bakeev, Pharmaceutical Technology Europe, Sep. 2003 ECPS 2011/Future Manufacturing of Pharmaceuticals 4

So Solid lid fo form rms s of of Na Napro proxen xen So Sodium dium 53% RH DH Methanol-water mixture 20 days (64mol% methanol) MH AH 60 ° C 94% RH TH AH: Anhydrate, MH: Monohydrate, DH: Dihydrate, TH: Tetrahydrate ECPS 2011/Future Manufacturing of Pharmaceuticals 5

Ob Objective jective of of t the pr he present esent wor ork Alteration in physicochemical properties of NS, attributed to the anhydrate to hydrate transformation during processing, has been reported 1,2 However, till date no PAT tool has been evaluated for monitoring of phase transformation of NS during pharmaceutical processing..!! Therefore, the present study focuses on evaluating feasibility of NIR spectroscopy as a real-time monitoring tool 1 Bansal, P. et. al. Drug Dev. Ind. Pharm. 1994 , 20, 2151-2156; 2 Martino, P.D. et.al , J. Pharm. Sci. 2008 , 97, 5263-5273 . ECPS 2011/Future Manufacturing of Pharmaceuticals 6

Th Ther ermal mal Gr Grav avim imetri etric c An Anal alysis ysis 6.59% 12.03% 21.67% ECPS 2011/Future Manufacturing of Pharmaceuticals 7

PX PXRD RD pa patt tterns erns Note:The dotted diffractograms are the calculated patterns for AH and MH forms from their crystal structures ECPS 2011/Future Manufacturing of Pharmaceuticals 8

FTI TIR R spe spect ctra ra 1229 ECPS 2011/Future Manufacturing of Pharmaceuticals 9

NIR Spe IR Spect ctra ra (S (SNV V co corr rrect ected) ed) O-H C-H O-H 1 st C-H 1 st combination combination Overtone Overtone ECPS 2011/Future Manufacturing of Pharmaceuticals 10

Ch Chemical emical in info forma rmation ion fr from om FT FTIR a IR and d NI NIR R sp spec ectra ra 1229 st O-H Soli lid O-H H stre retching tching 1 st H Ov Overt rton one st O-H 1 st H Ov Overt rton one (t (theo eoretical retical*) *) for orm (FTI (F TIR) R) (e (expe peri rimen ental # ) 6900 cm -1 (1449 nm) MH 3450 cm -1 1446 nm 6700 cm -1 (1492 nm) DH 3350 cm -1 1496 nm 6900-6760 cm -1 (1449-1479 nm) TH 3450-3380 cm -1 1447-1465 nm *calculated by multiplying the wave-number values for fundamental vibrations in FTIR spectra by 2; # observed by NIR spectroscopy ECPS 2011/Future Manufacturing of Pharmaceuticals 11

PCA PC A Sco Score res s plo lot fro t from m NIR spe IR spect ctral ral da data ta TH (Selected) 15 95% Confidence Level 10 MH TH Scores on PC 2 (13.63%) AH 5 0 DH -5 -10 -15 -30 -20 -10 0 10 20 30 Scores on PC 1 (81.62%) ECPS 2011/Future Manufacturing of Pharmaceuticals 12

PCA PC A Lo Load ading ings s pl plot fro t from m NIR spe IR spect ctral ral da data ta 0.08 0.06 0.04 Loadings on PC 1 (81.62%) Loadings on 0.02 PC1 0 -0.02 -0.04 -0.06 0.1 -0.08 1200 1400 1600 1800 2000 2200 Variable 0.08 0.06 Loadings on PC 2 (13.63%) 0.04 Loadings on 0.02 PC2 0 -0.02 -0.04 -0.06 1200 1400 1600 1800 2000 2200 Variable ECPS 2011/Future Manufacturing of Pharmaceuticals 13

Co Conclusion nclusion  NIR spectroscopy coupled with multivariate data analysis can efficiently distinguish the NS solid forms  NIR spectroscopy can be considered as a potential technique to monitor phase transformations  Further studies will focus on development of NIR based quantitative model that can be applied for real time monitoring of hydrate formation and dehydration behaviour of the NS solid forms during processing and storage ECPS 2011/Future Manufacturing of Pharmaceuticals 14

ECPS 2011/Future Manufacturing of Pharmaceuticals 15