Rapid quantitation of atorvastatin in process pharmaceutical powder sample using Raman spectroscopy and evaluation of parameters related to accuracy of analysis.

The purpose of this study was to determine the atorvastatin (ATV) content in process pharmaceutical powder sample using Raman spectroscopy. To establish the analysis method, the influence of the type of Raman measurements (back-scattering or transmission mode), preparation of calibration sample (simple admixing or granulation), sample pre-treatment (pelletization), and spectral pretreatment on the Raman spectra was investigated. The characteristic peak of the active compound was more distinctively detected in transmission Raman mode with a laser spot size of 4mm than in the back-scattering method. Preparation of calibration samples by wet granulation, identical to the actual manufacturing process, provided unchanged spectral patterns for the in process sample, with no changes and/or shifts in the spectrum. Pelletization before Raman analysis remarkably improved spectral reproducibility by decreasing the difference in density between the samples. Probabilistic quotient normalization led to accurate and consistent quantification of the ATV content in the calibration samples (standard error of cross validation: 1.21%). Moreover, the drug content in the granules obtained from five commercial batches were reliably quantified, with no statistical difference (p=0.09) with that obtained by HPLC assay. From these findings, we suggest that transmission Raman analysis may be a fast and non-invasive method for the quantification of ATV in actual manufacturing processes.

Hierarchical economic potential approach for techno-economic evaluation of bioethanol production from palm empty fruit bunches.

A hierarchical four-level approach to determine economic potential (4-level EP) is proposed for preliminary techno-economic analysis of new processes. The 4-level EP includes input/output structure, process flow structure, heat integration (HI), and economic feasibility. Two case studies on a 30.2 t/d (or 12.7 million l/yr) bioethanol plant with and without jet fuel production from palm empty fruit bunches (EFB) were investigated by applying the 4-level EP. The plant flowsheet was established based on experiments in a 0.1t/d pilot plant, including sequential dilute acid and alkali pretreatment, and separate hydrolysis and fermentation (SHF). EP approached a more reliable value through the hierarchical 4-level EP. The heating energy was reduced considerably by HI. The product value was estimated at $0.8-$1.3/kg of equivalent bioethanol. It was suggested through sensitivity analysis that a large plant size, enhanced production yields, and capital cost reduction were necessary for the lignocellulosic bioethanol production to be profitable.