IR spectroscopic-grade potassium bromide was checked prior to usage through the loss on drying method based on the recommended British Pharmacopia (BP) procedure ¹³ , which involves introducing 1g of the sample into a dry bottle, reheating and reweighing until a constant weight is obtained.

Reference DS chemical standard was provided by Neopharma Pharmaceutical Manufacturing, Abu Dhabi, UAE. Three different DS commercial tablets were obtained from local pharmacies in Al Ain city, UAE, namely: Rumafen (diclofenac sodium 50 mg); Olfen TM 50 (diclofenac sodium 50 mg); and Diclogesic 50 (diclofenac sodium 50 mg).

The FTIR instrument IRAffinity-1 CE (Shimadzu®, Kyoto, Japan), equipped with MiracleTM Single Reflection Horizontal ATR Accessory (Pike® Technologies) and IResolution Software (Shimadzu, version 1.60; Parameters: Measurement mode: % transmittance; Apodization: Happ-Genzel; No of scans: 15; Resolution: 16.0; Range (cm ^-1): Min 700, Max 2000), was used for the screening and quantitative analysis in this study. Non-proprietary spreadsheet processing software could be used to analyze the raw data obtained. The samples were dried in an oven (WiseVen®, Won-032, S. Korea) and an analytical balance (AUW220D, Shimadzu®) was used for all weights.

A calibration curve was prepared from six different DS standard concentrations within the range of 0.2–1.0 % w/w. An appropriate quantity of DS was diluted with potassium bromide to get each concentration and was thoroughly ground in a mortar for 10 min to ensure sample homogeneity. Infrared spectra of each measurement were converted to the first derivative spectra. The area under the curve (AUC) of each calibration standard was measured in the range 1550–1605 cm ^-1. This band corresponds to the CO stretching of carboxylic sodium salts.

To determine the API content for the commercial tablets in this study, ten tablets were accurately and individually weighed, then the whole sample was finely powdered for each brand. Samples were prepared by mixing and thoroughly grinding an appropriate quantity of each tablet powder with potassium bromide to get 0.5% w/w of DS. 100 mg of the mixture was transferred to the diamond ATR top plate of the spectrometer over the diamond crystal. IR measurements were run in triplicate and the average was calculated for each run.

SPSS version 21 (SPSS Inc., Chicago, IL, USA) was used for descriptive and analytical statistics.

The proposed ART-FTIR analytical method was validated according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use guidelines ²³ .

Validation of the method included the following parameters: linearity, selectivity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision and robustness.

The proportional relationship between the AUC and concentration was evaluated by constructing a linear regression of five concentrations (0.2, 0.4, 0.6, 0.8, 1%). The excellent linearity obtained was indicated by the correlation coefficient value r ² = 0.9994. Table 1 shows the data analysis of the DS calibration curve and the linear relationship is presented in Figure 3a and 3b.

Selectivity is used to justify the ability of the method to accurately quantify the existence of DS in the presence of other pharmaceutical additives. The selectivity of our method was verified by comparing diclofenac tablets to pure diclofenac. Bands used for quantification were only unique to diclofenac. Figure 2a and 2b represents the direct and first derivative of ART-FTIR spectra, which indicate the CO high absorption band at 1550–1605 cm ^-1. The first derivative shows a clear band without any overlapping from the other peaks. Additionally, Figure 3c and 3d represents the direct and first derivative spectra of Olfen tablet, respectively. The obtained data represented in these figures showed no interference from the excipients and additives present in the tablet formulation.

The LOD is the lowest amount of analyte at which that an analyte can be detected. While the LOQ is the lowest amount of analyte at which an analyte can be measured accurately and precisely.

LOD = 3.3 σ / S ( Equation 1 )

LOQ = 10 σ / S ( Equation 2 )

Where σ is the standard deviation and S is the slope.

By applying Equation 1 and Equation 2, the obtained values of LOD and LOQ were 0.052757% and 0.159869%, respectively ( Table 1). The low values for both parameters indicate the high sensitivity of this study ²⁴ .

The accuracy of the method was evaluated using the calibration method. Three different brands (A, B, and C) of diclofenac tablets were analyzed. 10 tablets of each brand were crushed to a fine powder and mixed with KBr to prepare 0.5% w/w diclofenac/KBr. Mean recovery of Tablets A, B and C was calculated to be 99.8%, 101.5% and 99.4, respectively ( Table 2). The obtained results are in agreement with USP and BP recovery range for DS tablets ^{12, 13} .

The precision of the method was assessed by repeatability and intermediate precision studies. Repeatability and robustness analysis were performed by analyzing the 0.5% w/w (mixed with KBr) peak areas (AUC) of each brand. Three readings for each sample were recorded and analyzed in one day (for the intra-day precision) and two readings were recorded on two consecutive days (for the inter-day precision). The results were very precise, as represented by the standard deviations, which ranged between 0.008343 and 0.020255, while the percent relative standard deviation (% RSD) was between 1.26095 and 3.03781.

Harvard Dataverse: Utility of ATR-FTIR Spectroscopic Method as Green Tool for Pharmaceutical Analysis of Diclofenac Sodium Tablets. https://doi.org/10.7910/DVN/6SJZ7W ²⁵ .

Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).