Real-time predictions of drug release and end point detection of a coating operation by in-line near infrared measurements

• Published in: International journal of pharmaceutics Vol. 421; no. 2; pp. 237 - 243
• Main Authors: Gendre, Claire, Boiret, Mathieu, Genty, Muriel, Chaminade, Pierre, Pean, Jean Manuel
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.12.2011; Elsevier
• Subjects: Biological and medical sciences; Cellulose - analogs & derivatives; Cellulose - chemistry; Chemical and Process Engineering; Citrates - chemistry; Coating operation; composite polymers; Computer Systems; Delayed-Action Preparations - chemistry; Dissolution testing; Drug Compounding; drug formulations; drugs; End point determination; Engineering Sciences; General pharmacology; guidelines; least squares; Materials; Medical sciences; Models, Theoretical; Near infrared spectroscopy (NIRS); normal values; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyvinyls - chemistry; prediction; Process analytical technology (PAT); Reproducibility of Results; Solubility; Spectroscopy, Near-Infrared; Sustained release tablets; Tablets, Enteric-Coated - chemistry; Process analytical technology (PAT); Sustained release tablets; Near infrared spectroscopy (NIRS); Dissolution testing; Coating operation; End point determination; Measurement; Coating material; Pharmaceutical technology; Controlled release form; Prediction; Drug carrier; Process; Dissolution; Near infrared spectrometry; Dosage form; Tablet; Coating; Detection; Quantitative analysis
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.09.036

The aim of this work was to carry out real-time near infrared (NIR) predictions of drug release from sustained release coated tablets and to determine end point of coating operation. In-line measurements were ensured by implementation of a NIR probe inside a pan coater. Tablets were coated using a functional aqueous dispersion of ethylcellulose blended with PVA–PEG graft copolymer to obtain a controlled drug release dosage form over 16h. Samples were collected at regular intervals and subjected to a standardized curing step. Percentages of released drug at 4h, 8h and 12h were selected to describe the controlled drug release of cured tablets. These dissolution criteria were used as reference values to calibrate NIR spectral information and to develop three partial least squares regressions. Low predictive errors of 1.7%, 1.9% and 1.5%, respectively, were obtained. The coating operation was stopped while desired dissolution criteria were achieved, corresponding to a coating level around 10%. The present study demonstrated that real-time NIR measurements could be performed on non-finished drug products to predict dissolution properties of cured coated tablets. This novel and innovative approach fulfils the expectations of ICH Q8 guideline on pharmaceutical development, in terms of process understanding and process analytical technology (PAT) control strategy. This approach should be however adapted to curing operation to allow a real-time release testing.