A study on the applicability of in-line measurements in the monitoring of the pellet coating process.
Special populations including paediatric and elderly patients often need advanced approaches in treatment, such as one-a-day dosing, which is achieved with modified release formulations or alternative routes of applications such as nasogastric route. Pellets are a dosage form that is frequently used in such formulations. The aim of the present work was to study the applicability of two in-line techniques, namely, Near Infrared Spectroscopy (NIR) and Spatial Filtering Technique (SFT) in the pellet coating process. The first objective of our work was to develop a prediction model for moisture content determination with the in-line NIR and to test its robustness in terms of sensitivity to changes in composition of the pellets and performance in wide range of moisture content. Secondly, the in-line SFT measurement was correlated with different off-line particle size methods. The third objective was to evaluate the ability of both in-line techniques for the detection of undesired deviations during the process, such as pellet attrition and agglomeration. Finally, the ability to predict coating thickness with the in-line NIR probe was evaluated. Results suggested that NIR prediction model for moisture content was less robust outside the calibration range and was also sensitive to changes in composition of the film coating. Nevertheless, satisfactory prediction was achieved in the case when coating composition was partially altered and adequate calibration range was used. The SFT probe results were in good correlation with off-line particle size measurement methods and proved to be an effective tool for coating thickness determination during the coating, however, the probe failed to accurately show the actual amount of the agglomerates formed during the process. In experiment when pellet attrition was initiated, both probes successfully detected abrasion of the pellet surface in real time. Furthermore, a predictive NIR model for coating thickness was made and showed a good potential to measure coating thickness in-line, suggesting that the NIR probe can be used as a single tool to monitor water content, coating thickness, and deviations in the coating process.
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8000 Novo mesto, Slovenia.
Grega
G
Hudovornik
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8000 Novo mesto, Slovenia.
Klemen
K
Korasa
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8000 Novo mesto, Slovenia; University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia. Electronic address: franc.vrecer@krka.biz.
Franc
F
Vrečer
D000180:Acrylic Resins / Q000737:chemistry; D002951:Citrates / Q000737:chemistry; D004304:Dosage Forms; D004339:Drug Compounding / Q000379:methods*; D008962:Models, Theoretical; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared; D013627:Talc / Q000737:chemistry
D000180:Acrylic Resins; D002951:Citrates; D004304:Dosage Forms; D011108:Polymers; D011109:Polymethacrylic Acids; D013627:Talc; C038300:methylmethacrylate-methacrylic acid copolymer; C050528:Eudragit RS; C058665:Eudragit RL; C023001:ethyl citrate
Controlled release coated pellets; In-line near infrared spectroscopy; Process analytical technology; Real time monitoring; Spatial filtering technique