Characterisation of transmission Raman spectroscopy for rapid quantitative analysis of intact multi-component pharmaceutical capsules.

A detailed characterisation of the performance of transmission Raman spectroscopy was performed from the standpoint of rapid quantitative analysis of pharmaceutical capsules using production relevant formulations comprising of active pharmaceutical ingredient (API) and 3 common pharmaceutical excipients. This research builds on our earlier studies that identified the unique benefits of transmission Raman spectroscopy compared to conventional Raman spectroscopy. These include the ability to provide bulk information of the content of capsules, thus avoiding the sub-sampling problem, and the suppression of interference from the capsule shell. This study demonstrates, for the first time, the technique's insensitivity to the amount of material held within the capsules. Different capsules sizes with different overall fill weights (100-400 mg) and capsule shell colours were assayed with a single calibration model developed using only one weight and size sample set (100 mg) to a relative error of typically <3%. The relative root mean square error of prediction of the concentration of API for the main sample set (nominal content 75%, w/w) was 1.5% with a 5s acquisition time. Models built using the same calibration set also predicted the 3 low level excipients with relative errors of 5-15%. The quantity of API was also predicted (with a relative error within ∼3%) using the same model for capsules prepared with different generations of API (i.e. API manufactured via different processes). The study provides further foundation blocks for the establishment of this emerging technique as a routine pharmaceutical analysis tool, capitalising on the inherently high chemical specificity of Raman spectroscopy and the non-invasive nature of the measurement. Ultimately, this technique has significant promise as a Process Analytical Technology (PAT) tool for online production application.

Use of a static eliminator to improve powder flow.

Glidants and lubricants have long been used to improve the flow and processing of pharmaceutical and other powder blends. In this letter, we find that similar improvements can be attained, without additives, by using a simple static eliminator. These results indicate, first, that electrostatic effects on powder blends may be a significant cause of powder aggregation and flow instabilities, and second, that common additives such as magnesium stearate, colloidal silica, and talc may have as their chief effect the reduction of static. This suggests both that intelligent placement of static eliminators can eliminate the need for some of these additives and that judicious engineering of ionic and cationic additives may be effective in improving flow of "clingy" materials.

Non-invasive quantitative assessment of the content of pharmaceutical capsules using transmission Raman spectroscopy.

This study demonstrates how transmission Raman spectroscopy can be used in the quantitative, non-invasive probing of the bulk content of production line relevant pharmaceutical products contained within capsules with a strong interfering Raman signal (principally TiO(2)). This approach is particularly beneficial in situations where the conventional Raman backscattering method is hampered or fails due to excessive Raman or fluorescence signals emanating from surface layers (capsule or coating) that pollute the much weaker subsurface Raman signals. In these feasibility experiments the interfering surface Raman signal was effectively suppressed, relative to the Raman signal of the internal content, by a factor of 33, in the transmission geometry in comparison with the conventional backscattering Raman approach. In conjunction with the superior bulk probing ability of the transmission Raman geometry, which effectively removes the sub-sampling problem inherent to conventional Raman spectroscopy, and multivariate analysis (principal component analysis (PCA), partial least squares (PLS) and classical least squares (CLS) regression), this provides an analytical tool well suited for rapid control monitoring applications in the pharmaceutical industry. The measured relative root mean square error of prediction (RMSEP) of the concentration of the active pharmaceutical ingredient (API) was 1.2 and 1.8% with 5 and 1s acquisition times, respectively.

Effect of moisture and magnesium stearate concentration on flow properties of cohesive granular materials.

In this article the gravitational displacement rheometer (GDR) is used to characterize the effects of formulation composition and environmental conditions (moisture) on flow properties of cohesive pharmaceutical powders under unconfined conditions. The amount of moisture in the sample often has important effects on the physical and chemical properties of pharmaceutical solids. Properties such as flow, compaction, disintegration, dissolution, hardness and chemical stability are all influenced by moisture. In the case of lactose, as moisture content increases in the powder bed, the flowability becomes poorer as the moisture condenses on the surface and increases cohesion. The celluloses show opposite effect as compared to lactose. Here, as moisture content increases, the flow properties improve dramatically. The GDR also captures the effect of lubricant concentration on the cohesion of powders. The presence of lubricant does not play any significant impact for free flowing powders, but as powder cohesion increases, the lubricants allow for improved flowability of powders. The GDR was also used for a case study of real drug formulation. The methodology was able to evaluate the impact of humidity and lubricant concentration on the flow properties of the formulation.

Applications of attenuated total reflection infrared spectroscopic imaging to pharmaceutical formulations.

This paper demonstrates an approach to obtain chemical images of pharmaceutical tablets using attenuated total reflection infrared (ATR-IR) spectroscopy. FT-IR images with different fields of view and spatial resolution have been obtained using a combination of different ATR accessories. FT-IR imaging with the diamond ATR accessory and micro-ATR imaging technique have been compared. With the diamond ATR imaging accessory, compaction to a tablet can be performed and the chemical image measured in situ. It has been found that the diamond ATR imaging accessory gives information on the overall distribution of different components in a tablet while the micro-ATR imaging technique provides a closer look at the tablet with 4-microm spatial resolution. Low-concentration components down to 0.5% have been detected by the micro-ATR method. Both experimental and commercial systems are studied in this paper.