In-line ATR-UV and Raman Spectroscopy for Monitoring API Dissolution Process During Liquid-Filled Soft-Gelatin Capsule Manufacturing

Wan, Boyong; Zordan, Christopher A.; Lu, Xujin; McGeorge, Gary

doi:10.1208/s12249-015-0456-0

Cited by 7 publications

(6 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Combining portable Raman spectroscopy with dissolution methods opens up opportunities to monitor processes without further sample preparation or aliquot removal. This may have application in the area of monitoring real-time API release [24] using small-footprint spectrometers [25] that can be implemented in the continuous process environment [26].…”

Section: Resultsmentioning

confidence: 99%

Quantitative determinations using portable Raman spectroscopy

Navin

Tondepu

Toth

et al. 2017

Journal of Pharmaceutical and Biomedical Analysis

View full text Add to dashboard Cite

A portable Raman spectrometer was used to develop chemometric models to determine percent (%) drug release and potency for 500mg ciprofloxacin HCl tablets. Parallel dissolution and chromatographic experiments were conducted alongside Raman experiments to assess and compare the performance and capabilities of portable Raman instruments in determining critical drug attributes. All batches tested passed the 30min dissolution specification and the Raman model for drug release was able to essentially reproduce the dissolution profiles obtained by ultraviolet spectroscopy at 276nm for all five batches of the 500mg ciprofloxacin tablets. The five batches of 500mg ciprofloxacin tablets also passed the potency (assay) specification and the % label claim for the entire set of tablets run were nearly identical, 99.4±5.1 for the portable Raman method and 99.2±1.2 for the chromatographic method. The results indicate that portable Raman spectrometers can be used to perform quantitative analysis of critical product attributes of finished drug products. The findings of this study indicate that portable Raman may have applications in the areas of process analytical technology and rapid pharmaceutical surveillance.

show abstract

Section: Resultsmentioning

confidence: 99%

Quantitative determinations using portable Raman spectroscopy

Navin

Tondepu

Toth

et al. 2017

Journal of Pharmaceutical and Biomedical Analysis

View full text Add to dashboard Cite

show abstract

“…7 Attempted treatment of these temperature-dependent responses via SNV and MSC, for UV spectra to monitor solute concentration during dissolution, did not afford significant improvement. 3 LSS may be more effective, as demonstrated for IR data. 42 Here, we report the application of UV and IR spectrometries for the determination of solubility diagrams for a model compound L-ascorbic acid (LAA, Chart 1) in an MeCN/H 2 O (80:20 w/w) solvent mixture.…”

Section: ■ Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 89%

“…Although LSS has been applied to IR data to remove the effects of temperature, especially where common preprocessing methods such as standard normal variate (SNV) and multiplicative scattering correction (MSC) were less effective, its application to UV data has not been reported. Variations in temperature result in changes to the peak position, width, and/or absorbance of UV spectra owing to changes in the electronic environment from solute–solvent interactions, , which has been observed with in-line UV measurements of solute concentration during crystallization processes. , For ATR measurements, temperature sensitivity can also be ascribed to changes in solution density and path length (penetration depth of the evanescent wave changes owing to temperature-induced changes in the refractive index of the liquid medium), while changes in the refractive index for the sapphire crystal are neligible . Attempted treatment of these temperature-dependent responses via SNV and MSC, for UV spectra to monitor solute concentration during dissolution, did not afford significant improvement .…”

Section: Introductionmentioning

confidence: 99%

“…Accurate determination of solute concentration is critical to many industrial processes, including solubility determination, 1 crystallization, 2 and dissolution. 3 Within the pharmaceutical industry, there has been increasing interest in quality by design approaches 4 , 5 to tackle variability in processes. Key drivers for these methodologies are cost reduction and maximizing operational efficiency.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Temperature Correction of Spectra to Improve Solute Concentration Monitoring by In Situ Ultraviolet and Mid-Infrared Spectrometries toward Isothermal Local Model Performance

Chong

McGlone

Chai

et al. 2022

Org. Process Res. Dev.

View full text Add to dashboard Cite

Changes in temperature can significantly affect spectroscopic-based methods for in situ monitoring of processes. As varying temperature is inherent to many processes, associated temperature effects on spectra are unavoidable, which can hinder solute concentration determination. Ultraviolet (UV) and mid-infrared (IR) data were acquired for l-ascorbic acid (LAA) in MeCN/H2O (80:20 w/w) at different concentrations and temperatures. For both techniques, global partial least squares (PLS) models for prediction of LAA concentration constructed without preprocessing of the spectra required a high number of latent variables to account for the effects of temperature on the spectra (root mean square error of cross validation (RMSECV) of 0.18 and 0.16 g/100 g solvent, for UV and IR datasets, respectively). The PLS models constructed on the first derivative spectra required fewer latent variables, yielding variable results in accuracy (RMSECV of 0.23 and 0.06 g/100 g solvent, respectively). Corresponding isothermal local models constructed indicated improved model performance that required fewer latent variables in the absence of temperature effects (RMSECV of 0.01 and 0.04 g/100 g solvent, respectively). Temperature correction of the spectral data via loading space standardization (LSS) enabled the construction of global models using the same number of latent variables as the corresponding local model, which exhibited comparable model performance (RMSECV of 0.06 and 0.04 g/100 g solvent, respectively). The additional chemometric effort required for LSS is justified if prediction of solute concentration is required for in situ monitoring and control of cooling crystallization with an accuracy and precision approaching that attainable using an isothermal local model. However, the model performance with minimal preprocessing may be sufficient, for example, in the early phase development of a cooling crystallization process, where high accuracy is not always required. UV and IR spectrometries were used to determine solubility diagrams for LAA in MeCN/H2O (80:20 w/w), which were found to be accurate compared to those obtained using the traditional techniques of transmittance and gravimetric measurement. For both UV and IR spectrometries, solubility values obtained from models with LSS temperature correction were in better agreement with those determined gravimetrically. In this first example of the application of LSS to UV spectra, significant improvement in the predicted solute concentration is achieved with the additional chemometric effort. There is no extra experimental burden associated with the use of LSS if a structured approach is employed to acquire calibration data that account for both temperature and concentration.

show abstract