Quality attributes and evaluation of pharmaceutical glass containers for parenterals.

Pharmaceutical containers for parenterals have been predominantly manufactured using glass as a packaging material of choice, especially Type-I glass, since it has been regarded as a chemically inert and an effective container closure system (CCS). Nevertheless, there have been reports and recalls related to glass quality issues, such as breakage, flakes, and particles observed in marketed products. The novelty of this research is based on the knowledge gathered from our previously conducted risk assessments and establishing a comprehensive testing platform focused on risk factors for glass container failure modes and applicability to other types of pharmaceutical containers. The evaluation of container quality attributes was performed for three model glass vials using a mechanical and chemical durability testing platform: freeze-thaw, lyophilization, compression, scratch tests; visual inspection, pH, particle size analyses, extractable, leachable and imaging studies that were conducted under normal (4 and 25 °C), and stress condition (60 °C), respectively. The performance between the glass containers tested under certain stress conditions (failure modes) were variable and differentiated. The systematic platform testing approach shows the importance of lab-based risk evaluation in assessing common failure modes of pharmaceutical containers, since the quality attributes for injectable products are complex and can impact final product quality.

Screening of unapproved drugs using portable Raman spectroscopy.

We present a four-step screening approach for unapproved drugs. The screening approach is both qualitative and quantitative in design in order to determine if the sample under study contains the correct and acceptable amount of the declared active pharmaceutical ingredient. Four commercially-available unapproved antibiotic and antiviral drugs were used in this study. Out of the 40 individual samples tested, 100% of the samples matched for the declared active pharmaceutical ingredient with no false positives. Following this qualitative identification step, a quantitative assay was used to determine the potency of the product. The assay involves dissolving the sample in water and using a partial least squares model to predict the potency of the product. The average Raman potency results for the four products tested were compared with chromatographic reference methods and the spectroscopic data were found to be within ∼1-6% of those obtained with the reference method for the four products tested. The results indicate that aqueous-based Raman assays may be a suitable field-deployable alternative to traditional techniques run in a laboratory environment.

Quantitative determinations using portable Raman spectroscopy.

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.