Real time Raman imaging to understand dissolution performance of amorphous solid dispersions

Abstract

We have employed for the first time Raman spectroscopic imaging along with multi-variate curve resolution (MCR) analysis to investigate in real time and in-situ the dissolution mechanisms that underpin amorphous solid dispersions, with data being collected directly from the dosage form itself. We have also employed a novel rotating disk dissolution rate (RDDR) methodology to track, through the use of high-performance liquid chromatography (HPLC), the dissolution trends of both drug and polymer simultaneously in multi-component systems. Two formulations of poorly water-soluble felodipine in a polymeric matrix of copovidone VA64 which have different drug loadings of 5% and 50% w/w were used as models with the aim of studying the effects of increasing the amount of active ingredient on the dissolution performance. It was found that felodipine and copovidone in the 5% dispersion dissolve with the same dissolution rate and that no Raman spectral changes accompanied the dissolution, indicating that the two components dissolve as single entity, whose behaviour is dominated by water-soluble copovidone. For the 50% drug-loaded dispersion, partial RDDR values of both felodipine and copovidone were found to be extremely low. MCR Raman maps along with classical Raman/X-ray powder diffraction (XRPD) characterisation revealed that after an initial loss of copovidone from the extrudate the drug re-crystallises, pointing to a release dynamics dependent on the low water solubility and high hydrophobicity of felodipine. Raman imaging revealed different rates of transition from amorphous to crystalline felodipine at different locations within the dosage form.

The Combined Use of Imaging Approaches to Assess Drug Release from Multicomponent Solid Dispersions

“…To this end, it is beneficial to combine standard USP-type dissolution tests with chemically specific, spectroscopic imaging-based analytical approaches such as attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic imaging (21–24), magnetic resonance imaging (MRI) (25,26), UV imaging (27,28) and Raman imaging (29,30). These techniques allow the visualization of dynamic physico-chemical processes within a tablet under dissolution conditions, making it possible to elucidate phenomena that could not be easily identifiable from the USP release curve.…”

The effect of drug and EUDRAGIT® S 100 miscibility in solid dispersions on the drug and polymer dissolution rate

“…The rotating disk method suppresses these factors due to the surface area and fluid mechanics of the system 10 . The dissolution profile of DPH in the DPH/S100 75 % solid dispersion did not fit to a linear regression (data not shown).…”

“…Drug crystallization in the solid dispersion is prompted by water 27, 28 . Recently, Francesco et al, investigated the dissolution of felodipine and copovidone V64 from the solid dispersion using a newly developed system, the rotating disk dissolution rate (RDDR) methodology 10 . At a low loading ratio (5 %), felodipine and copovidone dissolved simultaneously in the solid dispersion, while the dissolution rates of the two components were very different at a high drug loading (50 %).…”

In-line ATR-UV and Raman Spectroscopy for Monitoring API Dissolution Process During Liquid-Filled Soft-Gelatin Capsule Manufacturing

“…In addition, Raman has low interference from water that makes it ideal for analysis of aqueous solutions. It has been used for in situ monitoring of drug dissolution kinetics during drug product development (31)(32)(33). However, since Raman spectroscopy is essentially a single-beam technique, Raman signal intensity can be liable to instrumental variations and changes in sampling conditions as well.…”