Jun Zhao

Traditional wet chemistry methods, such as titration or high performance liquid chromatography (HPLC), require complete dissolution of the tablets in suitable solvents, which destroy the samples, create waste, and can be labor intensive and time consuming. Vibrational spectroscopic techniques, notably near-infrared (NIR) absorption and Raman scattering, are nondestructive, fast, and require no consumables. Transmission Raman spectroscopy (TRS) is particularly promising, due to its ability to sample a large portion of the sample’s volume.


QTRam is a compact transmission Raman analyzer designed specifically for content uniformity analysis of pharmaceuticals in solid dosage forms. In this note, we use a model drug, acetaminophen, to demonstrate the capability of QTRam to quantify low concentrations of API in compressed tablets.


QTRam is used to measure transmission Raman spectra of the uncoated tablets. The interrogated sample area is 4 mm in diameter as set by the excitation and collection apertures. BWAnalyst®, the 21 CFR pt 11 compliant software for QTRam, is used to collect all spectra. Each spectrum is an average of 10 scans, and each scan takes 3 s. Two or three spectra were acquired from each tablet sample.





Acetaminophen, also known as paracetamol and APAP, is chosen as a model API in this study, due to its availability and low toxicity. We target a hypothetical formulation of 1.5 mg API in a 300 mg tablet, for example, 0.5% APAP w/w. Nine blends were prepared, consisting of APAP, mannitol, silicified microcrystalline cellulose (MCC), croscarmellose, and magnesium stearate (MgSt). The blended powders are compressed into round tablets of 10 mm diameter and 3.0 mm thickness, each weighing roughly 300 mg.



For quantification, partial least squares (PLS) regression models are built using B&W Tek’s chemometric software BWIQ®. Assuming the API is distributed uniformly in the scale of the interrogated volume, we use the blend concentration as the reference for the individual tablets. Eight tablets are used from each blend, which should reduce the calibration error caused by unideal uniformity by way of averaging.


The QTRam is capable of fast and accurate analysis for content uniformity of low-dose pharmaceutical tablets.


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Articles

Compressed tablet is the most common form of orally administered drug. The United States Pharmacopeia (USP) chapter <905> requires that dosage uniformity of such products containing less than 25 mg or less than 25% active pharmaceutical ingredients (API) by weight must be analyzed for content uniformity, which is based on the assay of each API in a number of individual dosage units. 

Jun Zhao

Articles

QTRam for Content Uniformity Analysis of Low-Dose Pharmaceutical Tablets