Real-time on-line blend uniformity monitoring using near-infrared reflectance spectrometry: A noninvasive off-line calibration approach

Sulub, Yusuf; Wabuyele, Busolo Wa; Gargiulo, Paul; Pazdan, James; Cheney, James L.; Berry, Joseph K.; Gupta, Abhay; Shah, Rakhi B.; Wu, Hsien-Ming; Khan, Mansoor A.

doi:10.1016/j.jpba.2008.10.001

Cited by 73 publications

(47 citation statements)

References 15 publications

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“…9) The in-line NIRS system is used to determine the end of the blending process so that blending can be terminated at the optimum time for each production batch according to in-line data. [10][11][12][13][14][15] Previous studies have used an NIRS system to monitor the homogeneity of a lubricant. 16,17) However, the blend uniformity of lubricant as well as the change in the flatting state of the lubricant must be monitored during the lubrication process.…”

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Application of Terahertz Attenuated Total Reflection Spectroscopy to Detect Changes in the Physical Properties of Lactose during the Lubrication Process Required for Drug Formulation

Dohi

Momose

Yamashita

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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Manufacturing the solid dosage form of an orally administered drug requires lubrication to enhance manufacturability, ensuring that critical quality attributes such as disintegration and dissolution of the drug product are maintained during manufacture. Here, to evaluate lubrication performance during manufacture, we used terahertz attenuated total reflection (THz-ATR) spectroscopy to detect differences in the physical characteristics of the lubricated powder. We applied a simple formulation prepared by blending granulated lactose as filler with magnesium stearate as lubricant. A flat tablet was prepared using the lubricated powder to acquire sharp THz-ATR absorption peaks of the samples. First, we investigated the effects of lubricant concentration and compression pressure on preparation of the tablet and then determined the effect of the pressure applied to samples in contact with the ATR prism on sample absorption amplitude. We focused on the differences in the magnitudes of spectra at the lactose-specific frequency. Second, we conducted the dynamic lubrication process using a 120-L mixer to investigate differences in the magnitudes of absorption corresponding to the lactose-specific frequency during lubrication. In both studies, enriching the lubricated powder with a higher concentration of magnesium stearate or prolonging blending time correlated with higher magnitudes of spectra at the lactose-specific frequency. Further, in the dynamic lubrication study, the wettability and disintegration time of the tablets were compared with the absorption spectra amplitudes at the lactose-specific frequency. We conclude that THz-ATR spectroscopy is useful for detecting differences in densities caused by a change in the physical properties of lactose during lubrication.Key words terahertz pulsed spectroscopy; attenuated total reflection; lubrication; lactose; magnesium stearate; evanescent waveThe manufacture of the tablet or capsule form of an orally administered drug requires blending of a lubricant with granules or other excipients, including the active pharmaceutical ingredient (API). This important process enhances the flow of the powder, 1) and thereby helps optimize manufacturing processes such as tableting and encapsulation. Factors such as the type of blender, rotation speed, lubrication time, batch and equipment size can affect the quality attribute of a drug product.2,3) The factors are generally determined according to scale-up theories to maintain the same physicochemical properties of a lubricated powder when changes are made to the equipment or production scale of the lubrication process. 4-7)However, even when using the same manufacturing conditions, we must consider variations in lubrication performance among batches of lubricated powders that are caused, for example, by differences in the physical characteristics of the lubricant or the physical characteristics of granules that are manufactured before the lubrication process. 8)To conduct real-time monitoring of the uniformity of the blended powder dur...

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mentioning

confidence: 99%

Application of Terahertz Attenuated Total Reflection Spectroscopy to Detect Changes in the Physical Properties of Lactose during the Lubrication Process Required for Drug Formulation

Dohi

Momose

Yamashita

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…As vantagens da espectroscopia no NIR na avaliação de processo de mistura de pós têm sido recentemente enfatizadas por diversos autores (LYON et al, 2002;RITCHIE et al, 2002;COGDILL et al, 2005;ALCALA, 2006b;TABASI et al, 2008;SULUB et al, 2009). Nesse sentido, a técnica tem sido proposta para substituir o método de rotina utilizado para comprovar a conformidade de lotes produzidos em escala comercial.…”

Section: Evolução Das Boas Práticas De Fabricação De Medicamentos (Bpfm)unclassified

“…Nesse sentido, a técnica tem sido proposta para substituir o método de rotina utilizado para comprovar a conformidade de lotes produzidos em escala comercial. Além disso, o método é não-destrutivo (SULUB et al, 2009), livre de reagentes, quase independente de operador, sensível, rápido, preciso e exato.…”

Section: Evolução Das Boas Práticas De Fabricação De Medicamentos (Bpfm)unclassified

“…A grande vantagem da espectroscopia no NIR refere-se à obtenção dos resultados em tempo real (MOES et al, 2008;SULUB et al, 2009 No que se refere às aplicações qualitativas, a espectroscopia no NIR tem resolvido vários problemas, tais como investigações preliminares das análises de mistura ou discriminação entre produtos similares. Com maior frequência, a técnica é utilizada na identificação de substâncias químicas puras por meio de biblioteca pré-existente de espectros de referência (BLANCO et al, 2000).…”

Section: Evolução Das Boas Práticas De Fabricação De Medicamentos (Bpfm)unclassified

“…Na sequência, determinam-se experimentalmente as propriedades de interesse por um método de referência. A análise quantitativa para avaliação do processo de mistura e compressão de formas farmacêuticas sólidas também foi relatada por Sulub et al (2009). Os autores utilizaram o modelo de calibração PLS, confirmando a eficiência do método e a transferência do mesmo, tendo em vista sua utilização na linha de produção.…”

Section: Princípios Básicos Relativos àS Atividades De Calibração: Esunclassified

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Avaliação do processo de fabricação de comprimidos de Captopril (25 mg): aplicação da tecnologia analítica de processo e de ferramentas da qualidade e estatística

Curtivo¹

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Palavras-chave: Tecnologia analítica de processo; espectroscopia de infravermelho próximo; validação do método; validação de processo; índices de capacidade. ABSTRACTThe Good Manufacturing Practices (GMP) for Medicinal Products point out that the pharmaceutical industry must direct efforts to understand the variation of the processes, including the sources, the level of variation and the variation impact on the process in characteristics of the product. The manufacturing process has shown meaningful changes, especially in the introduction of new analytical technologies that allow the process control in real time. The approach based on risk analyses and on the new Pharmaceutical Quality System is a central key for the GMP for the XXI century. The Regulatory Agencies have demanded the pharmaceutical industry to adhere the continuous improvement related to the performance of its processes and, consequently, the product quality. Thus, the present paper aimed the development and validation of the analytical method employing NIR spectroscopy as the assessment of manufacturing process of Captopril 25 mg tablets, using rational scientific approach. Regarding the process assessment, the following tools were adopted: analysis of failure modes and effects analysis (FMEA), control charts, capability indexes, as well as analysis of variance (ANOVA). The near-infrared spectroscopy was selected due to its greater speed in getting the results, simplicity in sample preparation, and multiplicity of analysis from a single reading and provide non-invasive feature. The results confirmed the suitability of this technology in quantitative assessment of Captopril on the steps of mixing powders and compression. The relative standard deviations for the determination of Captopril uniformity in the post mixtures and in the tablets employing NIR were 3,15 e 0,18%, respectively. In reference to the stability assessment and process capacity, the tools adopted permitted the understanding of the sources of variability, as well as the determination of their level in different phases of the process. The capacity indexes relating to Captopril uniformity (% p/v) in the powder mixture, the average weight of the tablet, the content uniformity and the % (p/v) dissolved Captopril, in the dissolution assay were 0,70, 1,94, 1,80 and 2,19, respectively.

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Quality by Design

Khan

2017

Comprehensive Quality by Design for Pharmaceutical Product Development and Manufacture

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Real-time on-line blend uniformity monitoring using near-infrared reflectance spectrometry: A noninvasive off-line calibration approach

Cited by 73 publications

References 15 publications

Application of Terahertz Attenuated Total Reflection Spectroscopy to Detect Changes in the Physical Properties of Lactose during the Lubrication Process Required for Drug Formulation

Application of Terahertz Attenuated Total Reflection Spectroscopy to Detect Changes in the Physical Properties of Lactose during the Lubrication Process Required for Drug Formulation

Avaliação do processo de fabricação de comprimidos de Captopril (25 mg): aplicação da tecnologia analítica de processo e de ferramentas da qualidade e estatística

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