title: Vibrational spectroscopy and microspectroscopy analyzing qualitatively and quantitatively pharmaceutical hot melt extrudates.
abstract: Since the last decade, more and more Active Pharmaceutical Ingredient (API) candidates have poor water solubility inducing low bioavailability. These molecules belong to the Biopharmaceutical Classification System (BCS) classes II and IV. Thanks to Hot-Melt Extrusion (HME), it is possible to incorporate these candidates in pharmaceutical solid forms. Indeed, HME increases the solubility and the bioavailability of these drugs by encompassing them in a polymeric carrier and by forming solid dispersions. Moreover, in 2004, the FDA's guidance initiative promoted the usefulness of Process Analytical Technology (PAT) tools when developing a manufacturing process. Indeed, the main objective when developing a new pharmaceutical process is the product quality throughout the production chain. The trend is to follow this parameter in real-time in order to react immediately when there is a bias. Vibrational spectroscopic techniques, NIR and Raman, are useful to analyze processes in-line. Moreover, off-line Raman microspectroscopy is more and more used when developing new pharmaceutical processes or when analyzing optimized ones by combining the advantages of Raman spectroscopy and imaging. It is an interesting tool for homogeneity and spatial distribution studies. This review treats about spectroscopic techniques analyzing a HME process, as well off-line as in-line, presenting their advantages and their complementarities.
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, Avenue de l'Hôpital 1, B36, B-4000 Liege, Belgium. Electronic address: lnetchacovitch@ulg.ac.be.
authors.forename: L
authors.initials: L
authors.lastname: Netchacovitch
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Pharmaceutical Technology, CHU, Avenue de l'Hôpital 1, B36, B-4000 Liege, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Thiry
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, Avenue de l'Hôpital 1, B36, B-4000 Liege, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: De Bleye
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, Avenue de l'Hôpital 1, B36, B-4000 Liege, Belgium.
authors.forename: P-F
authors.initials: PF
authors.lastname: Chavez
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Pharmaceutical Technology, CHU, Avenue de l'Hôpital 1, B36, B-4000 Liege, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Krier
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, Avenue de l'Hôpital 1, B36, B-4000 Liege, Belgium.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Sacré
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Pharmaceutical Technology, CHU, Avenue de l'Hôpital 1, B36, B-4000 Liege, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Evrard
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, Avenue de l'Hôpital 1, B36, B-4000 Liege, Belgium.
authors.forename: Ph
authors.initials: P
authors.lastname: Hubert
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, Avenue de l'Hôpital 1, B36, B-4000 Liege, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Ziemons
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000639:trends; D006358:Hot Temperature; D015591:Microspectrophotometry / Q000379:methods / Q000639:trends; D013059:Spectrum Analysis, Raman / Q000379:methods*; D014732:Vibration
keywords: Hot-Melt Extrusion; Hyperspectral imaging; Microspectroscopy; Process Analytical Technology; Vibrational spectroscopy