Insights into the early dissolution events of amlodipine using UV imaging and Raman spectroscopy

TY - JOUR

T1 - Insights into the early dissolution events of amlodipine using UV imaging and Raman spectroscopy

AU - Boetker, Johan P

AU - Savolainen, Marja

AU - Koradia, Vishal

AU - Tian, Fang

AU - Rades, Thomas

AU - Müllertz, Anette

AU - Cornett, Claus

AU - Rantanen, Jukka

AU - Østergaard, Jesper

PY - 2011/8/1

Y1 - 2011/8/1

N2 - Traditional dissolution testing determines drug release to the bulk, but does not enable an understanding of the events happening close to the surface of a solid or a tablet. UV imaging is a new imaging approach that can be used to study the dissolution behavior of chemical compounds. The UV imaging instrumentation offers recording of absorbance maps with a high spatial and temporal resolution which facilitates the abundant collection of information regarding the evolving solution concentrations. In this study, UV imaging was used to visualize the dissolution behavior of amlodipine besylate (amorphous and dihydrate forms) and amlodipine free base. The dissolution of amlodipine besylate was faster from the amorphous form than from the crystalline forms. The UV imaging investigations suggested that a solvent mediated phase transformation occurred for the amorphous amlodipine besylate and the amlodipine free base samples. Raman spectroscopy was used to confirm and probe the changes at the solid surface occurring upon contact with the dissolution media and verified the recrystallization of the amorphous form to the monohydrate. The combination of UV imaging and Raman spectroscopy is an efficient tool to obtain a deeper insight into the early events of the dissolution process.

AB - Traditional dissolution testing determines drug release to the bulk, but does not enable an understanding of the events happening close to the surface of a solid or a tablet. UV imaging is a new imaging approach that can be used to study the dissolution behavior of chemical compounds. The UV imaging instrumentation offers recording of absorbance maps with a high spatial and temporal resolution which facilitates the abundant collection of information regarding the evolving solution concentrations. In this study, UV imaging was used to visualize the dissolution behavior of amlodipine besylate (amorphous and dihydrate forms) and amlodipine free base. The dissolution of amlodipine besylate was faster from the amorphous form than from the crystalline forms. The UV imaging investigations suggested that a solvent mediated phase transformation occurred for the amorphous amlodipine besylate and the amlodipine free base samples. Raman spectroscopy was used to confirm and probe the changes at the solid surface occurring upon contact with the dissolution media and verified the recrystallization of the amorphous form to the monohydrate. The combination of UV imaging and Raman spectroscopy is an efficient tool to obtain a deeper insight into the early events of the dissolution process.

KW - Amlodipine

KW - Magnetic Resonance Spectroscopy

KW - Molecular Structure

KW - Solubility

KW - Spectrophotometry, Ultraviolet

KW - Spectrum Analysis, Raman

KW - Thermogravimetry

U2 - 10.1021/mp200205z

DO - 10.1021/mp200205z

M3 - Journal article

C2 - 21634435

SN - 1543-8384

VL - 8

SP - 1372

EP - 1380

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

IS - 4

ER -