Design Space Development for the Dropping Process of a Dripping Pill with Material Attributes Represented As the Scores from Principal Component Analyses of Spectra Data

Design space development for the dropping process of a dripping pill with material attributes represented as the scores from principal component analyses of spectra data

Xingchu Gong, Jichen Shen, Haibin Qu^*

 (Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences,

Zhejiang University, Hangzhou 310058, China)

Abstract

Yinxingye Diwan is a dripping pill preparation treating angina pectoris and cerebral infarction. It is made from Ginkgo biloba extract and PEG 4000. The pass rate and productivity of dripping pills were considered as critical quality attributes (CQAs) of dropping process. Plackett-Burman designed experiments were performed to investigate the effects of materials and process parameters. The two materials of Ginkgo biloba extracts and PEG 4000 have significant effects on the process CQAs. The distance between dropping needle and condensate, and dropping speed were critical process parameters (CPPs). Split-plot designed experiments then were carried out to model the dropping process. Material properties were measured by near infrared spectroscopy (NIR) for Ginkgo biloba extracts and PEG 4000. The scores from principal component analyses (PCA) of NIR spectra were used in model development. Models with and without interaction terms between PCA scores and CPPs were compared. PCA scores with significant effects on the process CQAs were considered as critical material attributes (CMAs). After favorable model was selected, design space was developed based on the probability to attain process CQA limits. The probability was calculated using a Monte-Carlo simulation method. The design space then was verified using new materials. The quality levels of Ginkgo biloba extracts and PEG 4000 were also set according to PCA scores.