Putting NIR to Good Use in Tablet Formulation and Manufacture

Oral-solid dosage (OSD) forms remain a popular choice for both pharmaceutical companies and patients. Convenience, ease of manufacture and administration, increased stability, and simplicity for pack and transport-compared with alternative dosage forms-are some of the factors leading to the continued popularity of OSDs.

According to market research, the global OSD formulation market is anticipated to grow by an annual compound rate of 6.5%, reaching a value of US$926.3 billion (EUR826 billion) by the end of 2027 (1). As tablets comprise a significant proportion of OSD forms, within the pharma industry, tools that can aid in formulation and manufacturing efficiencies are of critical importance.

One such tool that finds use in tablet formulation and manufacture is near-infrared (NIR) spectroscopy. To learn more, Pharmaceutical Technology discussed the technique and its uses in greater detail with Federica Giatti, compression technologist at IMA Active Process Development R&D Laboratory. 

Useful in every step

PharmTech: Could you highlight the main uses of NIR specifically in tablet formulation and manufacture?

Giatti (IMA): NIR spectroscopy can be used in every step of the tablet formulation and manufacturing processes. For example, NIR is useful in tasks such as raw material identification, blend homogeneity, tablet characterization, and end-points determination in manufacturing critical process parameters. 

Thanks to the efficient and non-destructive method offered by NIR spectroscopy in the detection and quantification of physical and chemical characteristics of tablets, it is possible to quantify many tablet attributes, such as drug content, hardness, and dissolution, non-destructively from a single measurement. Additionally, NIR can be useful for in-line process control, where it can be used to monitor whether or not tableting is performed to the required quality level over time. The probe can deliver real-time data to prevent process deviations and stop the machine before powder has gone through the process area. Statistical post-process NIR analysis can be also implemented to verify, in a redundant way, the quality of tablets and compare with spectra acquired before. 

Considering several variables

PharmTech: Why is it important to analyze materials to be used in tableting, and how is NIR beneficial for these purposes? 

Giatti (IMA): Several variables should be taken into consideration in a common tableting process-variations in raw materials, deviations in granulation, or handling of all phases of formulation preparation could all affect the quality of the final blend.

Although NIR spectroscopy cannot be the primary analytical method for characterizing raw materials, its sensitivity to certain raw material characteristics (e.g., moisture content) allows for verification of the consistency between each API or excipient batch. 

In the granulation process stages, a process analytical technology (PAT) approach based on NIR sensors allows for the simultaneous determination of multiple parameters by measuring on-line residual moisture and particle enlargement during all phases of the granulation process by achieving the desired quality attribute phase-by-phase and not at a predetermined time. 

Verification of blend homogeneity is another interesting feature of NIR technology because it can lead to the avoidance of issues caused by thief sampling used in traditional content uniformity testing of powder blends. The spectral information can provide data about qualitative features of the blend (possibility to predict mixing end-point) or quantitative characteristics (API content) for building a specific calibration model.

Furthermore, NIR spectroscopy is useful when trying to keep process variations under control. A big advantage of the technique is real-time optimization of the process parameters by reducing the risk of batch rejection. This benefit is achievable as information about process or material properties can be obtained in a shorter period of time. 

Uses for dissolution testing

PharmTech: Can NIR provide significant benefits in dissolution testing? 

Giatti (IMA): NIR spectroscopy has been evaluated by numerous investigators for predicting dissolution profiles in a PAT approach. The major benefits provided by the technique are that it is a fast, non-destructive method allowing users to overcome the issues of a potentially long, drawn-out analysis as well as the small sample size that is commonplace in standard dissolution tests. 

Moreover, dissolution can be predicted to a certain level of reliability through calibration model development (e.g., partial least squares) when API content is variable. In addition, as NIR spectroscopy can detect the physical characteristics of tablets or a powder blend, tablet hardness variation can be monitored with NIR spectra. It is well known that as strength increases, API release decreases, and so for this reason, if the NIR spectra are studied extensively, dissolution behavior can be accurately predicted.

What might the future hold?

PharmTech: In your opinion, what does the future hold in terms of NIR spectroscopy within tablet formulation and manufacture?

Giatti (IMA): Regarding the future, particularly looking toward continuous manufacturing, NIR spectroscopy can help in the prediction of deviations from a quality gold standard using post-process chemometric algorithms. Through the acquisition of spectra continuously over time, pharmaceutical developers and manufacturers will be able to define specific areas or sections of the process when critical process parameters are under control, and also when out-of-specifications occur. For the latter situation, it could be possible to set up an alarm that can stop the machine and as a result avoid batch rejections.

Reference

1. Future Market Insights, “Oral Solid Dosage Pharmaceutical Formulation Market: Emerging Markets of Latin America, APEJ, and MEA to Collectively Hold over 45% Market Value Share: Global Industry Analysis 2012–2016 and Opportunity Assessment 2017–2027,” futuremarketinsights.com, Market Report, July 18, 2017.