Determination of moisture content in lyophilized mannitol through intact glass vials using NIR micro-spectrometers

Abstract

Determination of moisture content in lyophilized solids is fundamental to predict quality and stability of freeze-dried products, but conventional methods are time-consuming, invasive and destructive. The aim of this study was to develop and optimize a fast, inexpensive, noninvasive and nondestructive method for determination of moisture content in lyophilized mannitol, based on an NIR micro-spectrometer instead of a conventional NIR spectrometer. Measurements of lyophilized mannitol were performed through the bottom of rotating glass vials by means of a reflectance probe. The root mean standard error of prediction (RMSEP) and the correlation coefficient (R 2 pred ), yielded by the pre-treatments and calibration method proposed, was 0.233% (w/w) and 0.994, respectively.Uniterms: Near-infrared spectroscopy. Lyophilization. Multivariate analysis. Moisture content. Mannitol. Micro-spectrometer.A determinação do conteúdo de umidade em sólidos liofilizados é fundamental para se prever a qualidade e a estabilidade de produtos liofilizados, mas os métodos convencionais consomem muito tempo, são invasivos e destrutivos. O objetivo desse estudo foi desenvolver e otimizar um método rápido, econômico, não invasivo e não destrutivo para a determinação do conteúdo de umidade em manitol liofilizado, com base em microespectrômetro de infravermelho próximo ao invés de um espectrômetro de infravermelho próximo convencional. As medidas de manitol liofilizado foram realizadas através do fundo de recipiente de vidro em rotação por meio de sonda de reflectância. A raíz do erro médio padrão de predição (RMSEP) e o coeficiente de correlação (R 2 pred ) obtidos pelo prétratamento e pelo método de calibração proposto foram, respectivamente, 0,233% (p/p) e 0,994. Uniterms: Espectroscopia de infravermelho próximo. Liofilização. Análise multivariada. Análise de unidade. Manitol. Microespectrômetro.

A nondestructive and noninvasive method to determine water content in lyophilized proteins using low‐field time‐domain NMR

“…This aspect is similar to that of NIR methods. The major advantage of TD NMR over KF, which is the gold standard for measuring total water content in pharmaceutical formulations, is that, like NIR methods, it is nondestructive and noninvasive. Besides that, the total experimental time per sample was reduced to less than 5 min, bringing an additional advantage over KF, which has longer sample preparation and measurement times.…”

“…An ideal method should perform fast, noninvasive, and nondestructive measurements with minimal or no sample preparation. Near infrared (NIR) is such a method that has been established by Muzzio et al, who showed that lyophilized mannitol can be thoroughly examined for moisture content without modifying the content of the lyophilized vials . Moreover, several reports have also been published for the determination of moisture content in lyophilized products by scanning through the bottom of vials …”

“…The present study was focused on measuring the total amount of water in a lyophilized monoclonal antibody product in a noninvasive, nondestructive, and fast way using a benchtop low‐field time‐domain nuclear magnetic spectroscopic (TD NMR) method, which is highly complementary to NIR spectroscopy . Although conventional high‐field NMR spectrometers can do the same, the advantage of TD NMR is that the samples can be handled in a noninvasive and nondestructive manner.…”

Spectroscopic Techniques for Nondestructive Quality Inspection of Pharmaceutical Products: A Review

“…Similarly, Grohganz et al (2009) also demonstrated a NIR technique for quantification of water in freeze-dried lyophilized mixtures and showed good model accuracy with a low error. Muzzio et al (2011) used NIR combined with PCR and PLS analysis for the prediction of water contents in lyophilized mannitol (mannitol was used as an excipient in lyophilized pharmaceutical products). The obtained results suggested that both PCR and PLS models are able to predict moisture content, with   of 0.99 (calibration) and 0.96 with RMSEP of 0.233% respectively.…”

Quality by Design for Biopharmaceutical Drug Product Development

“…An example of the use of PLS to determine moisture from NIR can be found in a study to develop and optimize a fast, inexpensive, noninvasive, and nondestructive method for determination of moisture content in lyophilized mannitol, based on an NIR microspectrometer instead of a conventional NIR spectrometer. (Muzzio et al 2011). b.…”