From the initial drug discovery process to ensuring the quality control of drugs before their distribution to the public, analysis remains an essential component of almost any pharmaceutical product. Image analysis, in particular, is extensively relied upon in pharmaceutical sciences for a wide range of purposes.
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Process Analytical Technology (PAT) Tools
By definition, PAT is used to describe the tools needed to implement quality by design (QbD) protocols within the pharmaceutical industry.
PAT tools are widely used to monitor every aspect of the drug manufacturing process to ensure that the final product is of the highest quality, all the while maintaining its specified drug characteristics.
Image analysis is an important aspect of PAT-based methods, as it is often utilized throughout the manufacturing process, as well as for the final inspection of drug products.
Image Analysis and Dosage
Compared with conventional techniques that have previously been used for the analysis of pharmaceutical dosage forms, image analytical methods offer several advantages. For example, the analysis of particle size distribution (PSD) has traditionally been achieved through sieve analysis. However, when image-based techniques are used over this conventional technique, researchers quickly obtain results in real-time, all the while simultaneously acquiring information on the particle shape.
Similar advantages can be observed when assessing the active pharmaceutical ingredient (API) content of a drug product through imaging tools as opposed to conventional techniques such as mass spectrometry and high-pressure liquid chromatography (HPLC). For example, imaging techniques are non-destructive, do not require the use of any chemicals, are quicker, and require much simpler sample preparation.
Suitability For All Formulation Types
An additional advantage of imaging analysis for pharmaceutical products is that it can be performed on practically any formulation.
Solid dosage forms such as powders, dry powder inhalers (DPIs), granules, pellets, solid microcapsules, solid self-emulsifying drug delivery systems (SEDDS), nanofibers, films, tablets, and capsules, for example, can all be analyzed through various imaging modalities.
Dry powders are almost always incorporated into the drug manufacturing process, as most pharmaceutical dosage forms involve the use of powder at some stage in their development.
The size and characteristics of dry powder particles have a significant influence throughout the entire drug manufacturing process. Some of the different physical characteristics of dry powders that can be examined through various imaging modalities include particle size, two-dimensional (2D) morphology, and morphometry of granular substances, as well as content uniformity and homology in mixed/blended powders.
Although imaging analysis for tablet and capsule manufacturing is similarly used to ensure the uniformity of contents of active ingredients, this analytical approach can also provide important information on the stability of these formulations under various storage conditions. For example, imaging analysis provides information on whether the color of the tablets has changed after exposure to different temperatures, moisture, light, and ventilation environments.
Similarly, the visual inspection of defects on tablets and capsules during their packaging can also be assessed using imaging analysis.
Image Analysis and Microstructure
The microstructure of a pharmaceutical drug refers to the absolute and relative size distributions of various components present within the formulation, as well as the presence of any void space.
The unique characteristics of a drug’s microstructure can have a significant impact on the activity of the drug. For example, the presence of API agglomerates within the drug’s microstructure can have a wide range of effects, including an increase in the potency of the drug or reduced dissolution.
In addition to agglomerates, the size of lubricant particles in the final dosage form of a drug can also impact the overall microstructure of a formulation, altering its overall performance.
The analysis of tablet microstructure plays a crucial role in the development and manufacturing of these formulations. A thorough understanding of a drug’s microstructure requires the researcher to understand the spatial distribution of the different ingredients and void space within the tablet.
Chemical imaging (CI) analytical techniques such as vibrational spectroscopy modalities, including near-infrared and Raman spectroscopy, are used to study a wide range of microstructural characteristics in drug formulations. These can include but are not limited to distribution homogeneity, particle size distribution, tablet dissolution, and API polymorphisms.
In addition to these CI approaches, energy dispersive X-ray spectroscopy (EDX) based on SEM (SEM/EDX) has also been studied for the microstructural analysis of drugs. This imaging approach differs from CI by instead collecting element-specific X-rays that are generated from the interaction between a constant energy electron beam and the sample.
Some of the different microstructural characteristics that can be analyzed by SEM/EDX include surface topography and elemental composition. This type of analysis can provide information on drug and excipient distribution within a drug, dissolution performance, as well as the presence of any potential surface contaminants.
As compared with CI methods, SEM/EDX is advantageous as it requires minimal sample preparation that could otherwise introduce artifacts during sample analysis.
References and Further Reading
Farkas, D., Madarasz, L., Nagy, Z. K., et al. (2022). Image Analysis: A Versatile Tool in the Manufacturing and Quality Control and Pharmaceutical Dosage Forms. Pharmaceutics 13(685). doi:10.3390/pharmaceutics13050685.
Ostergaard, J. (2018). UV Imaging in pharmaceutical analysis. Journal of Pharmaceutical and Biomedical Analysis 147; 140-148. doi:10.1016/j.jpba.2017.07.055.
Gupta, S., Omar, T., & Muzzio, F. J. (2021). SEM/EDX and Raman chemical imaging of pharmaceutical tablets: A comparison of tablet surface preparation and analysis methods. International Journal of Pharmaceutics 611. doi:10.1016/j.ijpharm.2021.121331.