Fiber-Array-Based Raman Hyperspectral Imaging for Simultaneous, Chemically-Selective Monitoring of Particle Size and Shape of Active Ingredients in Analgesic Tablets.

Timea Frosch,Juergen Popp,Elisabeth Wyrwich,Di Yan,Torsten Frosch

doi:10.3390/molecules24234381

Abstract

The particle shape, size and distribution of active pharmaceutical ingredients (API) are relevant quality indicators of pharmaceutical tablets due to their high impact on the manufacturing process. Furthermore, the bioavailability of the APIs from the dosage form depends largely on these characteristics. Routinely, particle size and shape are only analyzed in the powder form, without regard to the effect of the formulation procedure on the particle characteristics. The monitoring of these parameters improves the understanding of the process; therefore, higher quality and better control over the biopharmaceutical profile can be ensured. A new fiber-array-based Raman hyperspectral imaging technique is presented for direct simultaneous in-situ monitoring of three different active pharmaceutical ingredients- acetylsalicylic acid, acetaminophen and caffeine- in analgesic tablets. This novel method enables a chemically selective, noninvasive assessment of the distribution of the active ingredients down to 1 µm spatial resolution. The occurrence of spherical and needle-like particles, as well as agglomerations and the respective particle size ranges, were rapidly determined for two commercially available analgesic tablet types. Subtle differences were observed in comparison between these two tablets. Higher amounts of acetaminophen were visible, more needle-shaped and bigger acetylsalicylic acid particles, and a higher incidence of bigger agglomerations were found in one of the analgesic tablets.

Highlights

The primary goal of the pharmaceutical industry is the achievement of an economic production of high-quality products with efficient and safe therapeutic effects for patients who rely on medical treatment
Results and Discussion thorough chemical information across a defined sample area in a rapid way, the requirements can be met forRaman chemically selective in-process monitoring theshape size, shape and distribution of different imaging was applied to visualize the of size, and distribution of particles of acetylsalicylic acid, acetaminophen and caffeine with chemical selectively in two analgesic tablets
The potential of fiber-array based Raman spectroscopic imaging was presented as in-process control for rapid, chemically selective, and simultaneous analysis of particle shape, size and distribution of different active ingredients in tablets with high spatial resolution

Summary

Introduction

The primary goal of the pharmaceutical industry is the achievement of an economic production of high-quality products with efficient and safe therapeutic effects for patients who rely on medical treatment. Molecules 2019, 24, 4381 acetylsalicylic acid, can associate better They can form a network, in which smaller particles like the ones of caffeine can eventually be embedded, enabling a more stable mixture of these two APIs. A homogenous mixture is challenging to achieve when the particle sizes of the acetylsalicylic acid–caffeine complexes are not in the same size range as the acetaminophen particles. The homogeneous distribution of the three APIs in a volume-dosed product would not be ensured The dosage form, such as the tablet, is the form that comes into direct physiological contact with the patient. The knowledge regarding the ingredient parameters in the end product is of high relevance, because the size, shape, and distribution of the API particles have direct biopharmaceutical, (patho-)physiological and pharmacological consequences. In our study the synergistic analgesic effect of acetylsalicylic acid and acetaminophen combined with caffeine [4] is targeted in the two commercial tablets, Thomapyrin Intensiv® (T) and

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Results

Conclusion