Analytical technologies for real-time drug dissolution and precipitation testing on a small scale

Abstract

Objectives This review focuses on real-time analytics of drug dissolution and precipitation testing on a comparatively small scale. Key findings Miniaturisation of test equipment is an important trend in pharmaceutics, and several small-scale experiments have been reported for drug dissolution and precipitation testing. Such tests typically employ analytics in realtime. Fibre optic ultraviolet (UV) analytics has become a well-established method in this field. Novel imaging techniques are emerging that use visible or UV light; also promising is Fourier transform infrared imaging based on attenuated total reflection. More information than just a rate constant is obtained from these methods. The early phase of a dissolution process can be assessed and drug precipitation may eventually be observed. Some real-time techniques are particularly well suited to studying drug precipitation during formulation dispersion; for example, turbidity, focused beam reflectance measurement and Raman spectroscopy. Summary Small-scale dissolution tests equipped with real-time analytics have become important to screen drug candidates as well as to study prototype formulations in early development. Future approaches are likely to combine different analytical techniques including imaging. Miniaturisation started with mini-vessels or small vials and future assays of dissolution research will probably more often reach the level of parallel well plates and microfluidic channels.

In-line derivative spectroscopy as a promising application to a small-scale in vitro transfer model in biorelevant supersaturation and precipitation testing

“…In both cases, in vitro dissolution (IVD) and precipitation testing are key for the prediction of oral drug absorption in humans. As IVD testing is time‐consuming and labour‐intensive, the development of a suitable in‐line analytical method for complex biorelevant dissolution testing is of great interest for industrial and academic demands …”

“…The second aim was to implement an in‐line method, using ketoconazole as a model compound, to allow for a more meaningful prediction of dissolution and precipitation processes occurring during a dissolution or pH‐shift experiment of poorly soluble drugs. This is especially important in supersaturated and thermodynamically unstable states, where manual sampling techniques suffer from the lack of sophisticated and fast sample preparation methods and therefore potentially lead to inaccurate results, which is caused by sample ageing during the time‐consuming offline analytics . As currently in the literature available studies describe the use of the in vitro transfer model in combination with manual sampling techniques followed by HPLC analytics with a limited sampling frequency and potential sample ageing, the set‐up described in this work represents a novel approach for an automated in vitro transfer model using in‐line derivative spectroscopy.…”

“…As IVD testing is time-consuming and labourintensive, the development of a suitable in-line analytical method for complex biorelevant dissolution testing is of great interest for industrial and academic demands. [4] UV derivative spectroscopy is mentioned as an analytical tool in the European Pharmacopeia and in the USP, for example to enhance the resolution power of overlapping peaks. [5,6] Furthermore, it can be used for concentration analysis of dissolved drugs in dissolution studies.…”

Interlaboratory Validation of Small-Scale Solubility and Dissolution Measurements of Poorly Water-Soluble Drugs

“…In this study, interlaboratory differences of apparent solubility (S app ) and IDR measurements were evaluated with the aim to develop guidelines for measuring the IDRs of poorly soluble compounds when only available in limited amounts. Miniature dissolution methods are increasingly used in academic research and industry laboratories, 11,[16][17][18][19][20][21][22][23][24] but, to the best of our knowledge, there are no common, standardized experimental protocols for the mDISS Profiler.…”

Correlation between calculated molecular descriptors of excipient amino acids and experimentally observed thermal stability of lysozyme

“…Several methods for monitoring of drug dissolution from different dosage forms have been developed (Kuentz 2014). These include UV fiber optics (Mirza et al, 2009), UV imaging alone (Østergaard et al, 2014) or combined with Raman spectroscopy (Boetker et al, 2011), methods based on infrared (IR) (Coutts-Lendon et al, 2003) or near-infrared (NIR) spectroscopy (Sarraguça et al, 2016), potentiometric methods (Bohets et al, 2007) and optical particle analysis (Laitinen et al, 2016).…”