In Vitro Monitoring of Dissolution of an Immediate Release Tablet by Focused Beam Reflectance Measurement

Abstract

Changes in in vitro drug release profiles of oral dosage forms are commonly observed due to storage of drug product at elevated temperature and humidity. An example is presented of an immediate release drug product which underwent changes to both release profile and crystal form on storage at elevated humidity. The dissolution rate for unstressed tablets was comparable regardless of the crystal form present. Decreased release rate was only observed for stressed tablets that exhibited crystal form conversion. The cause of the dissolution change was determined by evaluating tablets manufactured with three drug substance crystal forms by fiber optic ultraviolet detection and focused beam reflectance measurement (FBRM). Tablets were also analyzed by near-infrared spectroscopy for crystal form determination. The observed change in dissolution rate correlated with detection of a greater number of larger particles by FBRM. FBRM results indicate increased aggregation of the tablet material due to crystal form conversion, resulting in the presence of slowly disintegrating and dissolving granules during the dissolution process. The improved understanding of the dissolution process allows evaluation of the potential in vivo impact of the stability changes.

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

“…studied particle distributions in the course of drug dissolution. This method complemented results from concentration analysis as obtained from fibre optic UV spectroscopy [115]. A biopharmaceutical use of FBRM was reported even earlier by Gao et al [43].…”

“…This method complemented results from concentration analysis as obtained from fibre optic UV spectroscopy. [115] A biopharmaceutical use of FBRM was reported even earlier by Gao et al [43] The authors investigated supersaturatable self-emulsifying drug delivery systems of the drug AMG 517. It was possible to study how formulation differences affected the kinetics of drug precipitation in aqueous dispersions.…”

A Review of Disintegration Mechanisms and Measurement Techniques

“…In general, a smaller particle size causes a faster dissolution (see Eq. 13) which was investigated by employing focused beam reflectance measurements (FBRM) [147, 148] Focused beam reflectance measurements and dynamic laser diffraction [149–151]. Several other studies used video imaging to count the number of detached particles and to measure their size [20, 43, 152, 153].…”

Effective sapphire repellency treatment to reduce fouling of a focused beam reflectance measurement (FBRM) probe in bituminous systems

“…Focused beam reflectance measurement (FBRM) is a measurement technique that allows for in‐situ dynamic measurements of particle or drop sizes in a process. The FBRM probe is used extensively in crystallization processes and a number of processes with a solid dispersed phase, as well as in the study of liquid/liquid dispersions and more recently it has been applied to crude oil systems . The FBRM probe directs a laser beam through a sapphire window into the fluid and collects backscattered light.…”