Dissolution testing is an assay commonly used during the drug product development stage as well as a part of the quality control (QC) testing of the final dosage forms of drug products. Concentration monitoring using in situ fiber optic UV automates the dissolution measurements eliminating uncertainties related to filter selection, timing of volume withdrawal, manual sample handling, etc. More and more drug products are reaching the market as combination of a several APIs making in situ approach difficult while HPLC is time and resource intensive. This study introduces a developed computational method for real time concentration measurements of multiple APIs using in situ fiber optic UV-Vis monitoring.

The rapid dissolution rate of many water-soluble,immediate release solid dosage forms requires a dissolution analyzer that is fast,sensitive,customizable for frequent measurements,and able to generate data of high precision and quality.These requirements fit perfectly with today’s in situ fiber optic technology.The Rainbow Dynamic Dissolution Monitor was used in this study to demonstrate and evaluate the dissolution behavior of 500 mg Vitamin B12 (cyanocobalamin) tablets in degassed water, simulated gastric fluid (SGF),and phosphate buffer at stirring speeds as high as 100 rpm. Upon dissolution,Vitamin B12 tablets produce rather turbid suspensions that may be expected to cause problems for in situ measurements. However, the effect of light scattering by suspensions is largely eliminated when the second derivative of the absorbance signal is used in quantitation. Excellent data correlation was observed between the different media and the standard when using this method.

It was demonstrated [1] that flux measurements provided more in-depth understanding of supersaturated systems than solute concentration measurements alone. Such measurements were further employed to characterize and explain the differences between brand name and generic drug products that were reported from the bioequivalence studies [2]. The benefits of flux measurements were based on the fact that they captured the complex interplay between effects of formulations on solubility, dissolution rate and permeability of an active pharmaceutical ingredient (API). From the other hand, there has not been a predictive model that would use flux measurements directly as an input parameter for calculation of maximum absorbable dose (MAD) or fraction of the API absorbed (Fa) from an oral dosage form. This study demonstrated a feasibility of using flux measurements through artificial membrane to predict Fa values in biopharmaceutics modelling for BCS Class 2 drugs.

It has been shown that miniaturized two stage in vitro dissolution test1 can be used to understand why some low soluble weak basic drugs show reduced or highly variable absorption when coadministered with pH-modifying agents. The goal of this study was to demonstrate that an absorption chamber combined with USP 1 and 2 dissolution apparatus can be used to study similar drug-drug interactions (DDI) of the final dosage forms.

For generic drug development traditional (USP) dissolution tests have been used in the pharmaceutical industry to compare performance of different drug product formulations before or instead of conducting bioequivalence studies. Although dissolution tests provide a simple way of testing formulations, the in vivo predictive power of these tests are questionable. Namely, when a poorly water-soluble API is formulated to enhance its dissolution, additives, such as surfactants and polymers have an effect not only on dissolution profile, but also on flux through the membrane. The aim of this study was to represent the importance of simultaneous dissolution-absorption studies using MacroFLUX apparatus before conducting bioequivalence studies.

This study was aimed at exploring the feasibility of conducting simultaneous dissolution testing of two actives, using a multi-channel UV-Vis fiber optic system and second derivative spectra, as an analytical technique to support real-time in vitro release profiling.