API Content and Blend Uniformity Using Quantum Cascade Laser Spectroscopy Coupled with Multivariate Analysis

The process analytical technology (PAT) initiative proposed by the US Food and Drug Administration (FDA) suggests innovative methods to better understand pharmaceutical processes. The development of analytical methods that quantify active pharmaceutical ingredients (APIs) in powders and tablets is fundamental to monitoring and controlling a drug product’s quality. Analytical methods based on vibrational spectroscopy do not require sample preparation and can be implemented during in-line manufacturing to maintain quality at each stage of operations. In this study, a mid-infrared (MIR) quantum cascade laser (QCL) spectroscopy-based protocol was performed to quantify ibuprofen in formulations of powder blends and tablets. Fourteen blends were prepared with varying concentrations from 0.0% to 21.0% (w/w) API. MIR laser spectra were collected in the spectral range of 990 to 1600 cm−1. Partial least squares (PLS) models were developed to correlate the intensities of vibrational signals with API concentrations in powder blends and tablets. PLS models were evaluated based on the following figures of merit: correlation coefficient (R2), root mean square error of calibration, root mean square error of prediction, root mean square error of cross-validation, and relative standard error of prediction. QCL assisted by multivariate analysis was demonstrated to be accurate and robust for analysis of the content and blend uniformity of pharmaceutical compounds.

STUDY OF DIRECT COMPRESSION METHOD FOR THE PREPARATION OF QUINAPRIL HYDROCHLORIDE TABLETS

Objective: Direct compression method is preferable for tablet manufacture. The direct compression method is followed for many formulations but the relevant study is not reported. The present work aims to study the suitability of the direct compression process to prepare tablets of quinapril hydrochloride (QHCl), a low dose drug with a starting dose of 5 mg, indicated in the treatment of hypertension, congestive heart failure, and other conditions. Methods: QHCl is reported to be unstable in the presence of moisture, heat, and some excipients. The direct compression method was tried instead of a wet granulation technique to prepare the tablets. Initially, drug-excipient compatibility study was carried out. For selected excipients and QHCl preformulation tests were conducted. The stabilizer was employed. Three formulations were tried. The blends were prepared by tumbling and trituration methods. Blend uniformity and precompression parameters were determined. Tablets were directly compressed and evaluated. Results: Drug-excipient compatibility was studied at 60°C and 40°C with an Relative humidity (RH) of 75% for 4 weeks. It showed discoloration of the pure drug and most of the drug excipient mixtures. Three formulations Q1, Q2, and Q3 were prepared using magnesium oxide (light), magnesium carbonate (light), and Aerosil as stabilizers. Blending was done by trituration and tumbling method for 10 min and 15 min duration for the given batch size. Blend uniformity was determined. Tumbling method for 15 min showed good blending as evident from the percentage coefficient of variation values. The blends had a good flow. Tablet evaluation showed hardness in the range of 2.5–3 kg/cm2 and disintegration time of 1–2 min. Q1 and Q2 passed the friability test. The content uniformity criterion was achieved with an acceptance value <20. In vitro dissolution, Q1 and Q2 were 100% and 98.8%, respectively, in 30 min and followed first-order kinetics. The stability study of Q1 indicated a single peak in the chromatogram corresponding to the drug. Q2 showed spotted discoloration. Conclusion: The direct compression technique could be employed for the preparation of QHCl tablets. Q1 showed better stability and release characteristics. Q2 and Q3 are considered for further study.