Use of real‐time FT‐IR monitoring of a pharmaceutical compound under stress atmospheric conditions to characterize its solid‐state degradation kinetics

Abstract

The use of online FT-IR is described for investigating the degradation kinetics of the solid amorphous pharmaceutical compound, fosaprepitant dimeglumine (FD), under stress storage conditions (i.e., high temperature, T, and humidity, % RH). It is found that under conditions of elevated T and % RH, the kinetics are denucleation rate limited for the deliquescence of the amorphous FD solid, based on the high quality fits obtained to the authors' dispersive kinetic model for that mechanism. At elevated T and low % RH, it is found that a classical, first-order hydrolysis mechanism for the degradation of FD (which forms crystalline aprepitant, AP) significantly contributes to the overall conversion rate. That mechanism is similar to the one observed previously for the solution-phase hydrolysis of FD. Appropriate kinetic models are proposed for the FD-to-AP conversion under all of the experimental conditions investigated in this work. C 2009 Wiley Periodicals, Inc. Int J Chem Kinet 42: 25

Use of Dispersive Kinetic Models for Nucleation and Denucleation to Predict Steady-State Nanoparticle Size Distributions and the Role of Ostwald Ripening

“…The dispersive kinetic models for nucleation and denucleation presented herein are simple and easy to use, and they provide a ready interpretation of the key physicochemical aspects of the kinetics via only two semiempirical parameters. ,,, In a recent work, the activation energy distributions relevant to those models were defined . In the present paper, a unique and attractive property of those models is leveraged to define the PSDs corresponding to nucleation and denucleation mechanisms: the ability to directly correlate the underlying activation energy distribution function to a t -invariant/stationary PSD function.…”

Mid‐infrared spectroscopy‐based antibody aggregate quantification in cell culture fluids

“…The wavenumber range 1300‐1100 cm –1 was not considered due to absorbance of the filter card used for sample measurement in the Direct Detect™ instrument. Shifts of bands as described in the literature were observed, such as a shift of beta‐sheet associated bands from around 1690 cm –1 to 1694 cm –1 Broadening of bands, associated with disordered structures [18–24] was also noted.…”

“…bioreactor culture samples or various phases of downstream processing, as mimicked by the here presented models using cell culture fluid with antibody addition and also using real process‐samples containing mAb B. Specific wavenumber regions used to estimate host cell protein impurities and antibody levels [20, 21] do not overlap with wavenumber ranges selected in this study, except for the region 1665‐1654 cm –1 , which can also be modified slightly to avoid interference with overall antibody quantification as described [21]. Thus, in principle, this multiple parameter estimation (mAb, host cell protein, mAb aggregation level) can be obtained with a single MIR measurement.…”

“…This allows aggregated antibody to be differentiated from non‐aggregated antibody, as well as from other unrelated substances. MIR has been used for quantification of antibody levels and host cell protein impurities (HCP) in cell culture fluid [15–17] and has also been used to analyze the effects of storage and formulation type on antibody structure [18–24]. Moreover, it has also been successfully applied to aggregate analysis [25–29].…”

At-line mid infrared spectroscopy for monitoring downstream processing unit operations

“…Thus, it has already been used for analyzing protein refolding [5], elucidating the effects of different storage temperatures and formulations on protein stability [6][7][8][9][10][11], quantification of different analytes in a fermentation process as well as for quantifying monoclonal antibody (mAb) amounts in mammalian cell culture [12,13].…”