Monitoring of the Manufacturing Process for Ambroxol Hydrochloride Tablet Using NIR-chemometric Methods: Compression Effect on Content Uniformity Model and Relevant Process Parameters Testing

Drug Dev Ind Pharm. 2015;41(11):1877-87. doi: 10.3109/03639045.2015.1019354. Epub 2015 Mar 4.

Abstract

This study aimed at using near-infrared (NIR) spectroscopy to monitor compaction pressure for simultaneously determining the tensile strength and content uniformity, as well as moisture and mean particle size of ambroxol hydrochloride tablets. The content uniformity, compression force and tensile strength of the laboratory samples were obtained by pressing a mixture of active principle and excipient components into tablets. To reduce the spectral baseline shift of the laboratory samples, the compaction pressure applied to the mixture was assessed by a variable pressure test. Production samples were added to the test and subjected to principal component analysis. The expanded partial least-squares (PLS) calibration model used to quantify the active content was more accurate than the model constructed from laboratory samples using the production tablets included in the calibration set. The model showed good predictability, with correlation coefficient (R) 0.9977. The validation and reliability of the content model were evaluated to determine trueness and reliability for the measurement of individual production tablets and the laboratory tablets with drug content ranging from 24 to 36 mg. The PLS calibration models for compression force and tensile strength were constructed using the same spectral set assuming both were highly related. These models yielded high R values (0.9955 and 0.9910). The R values of the moisture and mean particle size were 0.9994 and 0.9919, respectively. This study demonstrated that NIR spectroscopy combined with chemometric techniques can be successfully used to quantitatively monitor the tablet manufacturing process in the pharmaceutical industry.

Keywords: Ambroxol hydrochloride; PLS; chemometrics; compaction pressure; content uniformity; mean particle size; moisture content; near-infrared spectroscopy.

MeSH terms

  • Ambroxol / administration & dosage*
  • Ambroxol / chemistry
  • Calibration
  • Drug Compounding / methods
  • Excipients / chemistry*
  • Least-Squares Analysis
  • Models, Theoretical
  • Particle Size
  • Pressure
  • Principal Component Analysis
  • Reproducibility of Results
  • Spectroscopy, Near-Infrared / methods*
  • Tablets
  • Tensile Strength

Substances

  • Excipients
  • Tablets
  • Ambroxol