Simultaneous measurement of liquid-phase and solid-phase transformation kinetics in rotating disc and channel flow cell dissolution devices

Paula Lehto, Jaakko Aaltonen, Pentti Niemelä, Jukka Rantanen, Jouni Hirvonen, Veli Pekka Tanninen, Leena Peltonen

Research output: Contribution to journalArticleScientificpeer-review

18 Citations (Scopus)

Abstract

Solvent-mediated solid-phase transformations may occur during dissolution tests which complicates the evaluation of dissolution rates in cases of metastable drugs. The purpose of this study was to determine the effects of solvent-mediated transformations of theophylline anhydrate (TP (A)) on the intrinsic dissolution rate in simulated gastric fluid at pH 1.2. A combined method set-up for simultaneous measurement of the dissolved quantity of drug and the solid form composition was constructed from in situ Raman spectroscopy and UV–vis-spectrophotometry. Transformation kinetics in the traditional USP rotating disc (RD) dissolution apparatus was compared with the recently introduced channel flow cell (CFC). Solid-phase data, supported by scanning electron micrographs taken off-line, explained the changes in the intrinsic dissolution rates due to hydrate formation. Kinetic modelling showed that first order kinetics fitted the data in CFC, but the conversion in RD was strongly S-shaped. These differences were related to dissimilar hydrodynamic conditions and diffusion characteristics in the two dissolution testing devices. In situ solid-phase measurement during dissolution testing can largely improve the understanding of the dissolution results of metastable drugs. This information is valuable in drug candidate selection as well as in explaining and controlling the behaviour of drug substances in the final drug products.
Original languageEnglish
Pages (from-to)66-72
JournalInternational Journal of Pharmaceutics
Volume363
Issue number1-2
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fingerprint

Equipment and Supplies
Pharmaceutical Preparations
Raman Spectrum Analysis
Spectrophotometry
Hydrodynamics
Theophylline
Stomach
Electrons

Keywords

  • dissolution rate
  • solid state
  • raman spectroscopy
  • polymorphism
  • hydrates/solvates
  • rotating disc
  • channel flow cell
  • simulated gastric fluid

Cite this

Lehto, Paula ; Aaltonen, Jaakko ; Niemelä, Pentti ; Rantanen, Jukka ; Hirvonen, Jouni ; Tanninen, Veli Pekka ; Peltonen, Leena. / Simultaneous measurement of liquid-phase and solid-phase transformation kinetics in rotating disc and channel flow cell dissolution devices. In: International Journal of Pharmaceutics. 2008 ; Vol. 363, No. 1-2. pp. 66-72.
@article{decfb6e46ec04934bb6b0ac18e436ac4,
title = "Simultaneous measurement of liquid-phase and solid-phase transformation kinetics in rotating disc and channel flow cell dissolution devices",
abstract = "Solvent-mediated solid-phase transformations may occur during dissolution tests which complicates the evaluation of dissolution rates in cases of metastable drugs. The purpose of this study was to determine the effects of solvent-mediated transformations of theophylline anhydrate (TP (A)) on the intrinsic dissolution rate in simulated gastric fluid at pH 1.2. A combined method set-up for simultaneous measurement of the dissolved quantity of drug and the solid form composition was constructed from in situ Raman spectroscopy and UV–vis-spectrophotometry. Transformation kinetics in the traditional USP rotating disc (RD) dissolution apparatus was compared with the recently introduced channel flow cell (CFC). Solid-phase data, supported by scanning electron micrographs taken off-line, explained the changes in the intrinsic dissolution rates due to hydrate formation. Kinetic modelling showed that first order kinetics fitted the data in CFC, but the conversion in RD was strongly S-shaped. These differences were related to dissimilar hydrodynamic conditions and diffusion characteristics in the two dissolution testing devices. In situ solid-phase measurement during dissolution testing can largely improve the understanding of the dissolution results of metastable drugs. This information is valuable in drug candidate selection as well as in explaining and controlling the behaviour of drug substances in the final drug products.",
keywords = "dissolution rate, solid state, raman spectroscopy, polymorphism, hydrates/solvates, rotating disc, channel flow cell, simulated gastric fluid",
author = "Paula Lehto and Jaakko Aaltonen and Pentti Niemel{\"a} and Jukka Rantanen and Jouni Hirvonen and Tanninen, {Veli Pekka} and Leena Peltonen",
year = "2008",
doi = "10.1016/j.ijpharm.2008.07.001",
language = "English",
volume = "363",
pages = "66--72",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1-2",

}

Simultaneous measurement of liquid-phase and solid-phase transformation kinetics in rotating disc and channel flow cell dissolution devices. / Lehto, Paula; Aaltonen, Jaakko; Niemelä, Pentti; Rantanen, Jukka; Hirvonen, Jouni; Tanninen, Veli Pekka; Peltonen, Leena.

In: International Journal of Pharmaceutics, Vol. 363, No. 1-2, 2008, p. 66-72.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Simultaneous measurement of liquid-phase and solid-phase transformation kinetics in rotating disc and channel flow cell dissolution devices

AU - Lehto, Paula

AU - Aaltonen, Jaakko

AU - Niemelä, Pentti

AU - Rantanen, Jukka

AU - Hirvonen, Jouni

AU - Tanninen, Veli Pekka

AU - Peltonen, Leena

PY - 2008

Y1 - 2008

N2 - Solvent-mediated solid-phase transformations may occur during dissolution tests which complicates the evaluation of dissolution rates in cases of metastable drugs. The purpose of this study was to determine the effects of solvent-mediated transformations of theophylline anhydrate (TP (A)) on the intrinsic dissolution rate in simulated gastric fluid at pH 1.2. A combined method set-up for simultaneous measurement of the dissolved quantity of drug and the solid form composition was constructed from in situ Raman spectroscopy and UV–vis-spectrophotometry. Transformation kinetics in the traditional USP rotating disc (RD) dissolution apparatus was compared with the recently introduced channel flow cell (CFC). Solid-phase data, supported by scanning electron micrographs taken off-line, explained the changes in the intrinsic dissolution rates due to hydrate formation. Kinetic modelling showed that first order kinetics fitted the data in CFC, but the conversion in RD was strongly S-shaped. These differences were related to dissimilar hydrodynamic conditions and diffusion characteristics in the two dissolution testing devices. In situ solid-phase measurement during dissolution testing can largely improve the understanding of the dissolution results of metastable drugs. This information is valuable in drug candidate selection as well as in explaining and controlling the behaviour of drug substances in the final drug products.

AB - Solvent-mediated solid-phase transformations may occur during dissolution tests which complicates the evaluation of dissolution rates in cases of metastable drugs. The purpose of this study was to determine the effects of solvent-mediated transformations of theophylline anhydrate (TP (A)) on the intrinsic dissolution rate in simulated gastric fluid at pH 1.2. A combined method set-up for simultaneous measurement of the dissolved quantity of drug and the solid form composition was constructed from in situ Raman spectroscopy and UV–vis-spectrophotometry. Transformation kinetics in the traditional USP rotating disc (RD) dissolution apparatus was compared with the recently introduced channel flow cell (CFC). Solid-phase data, supported by scanning electron micrographs taken off-line, explained the changes in the intrinsic dissolution rates due to hydrate formation. Kinetic modelling showed that first order kinetics fitted the data in CFC, but the conversion in RD was strongly S-shaped. These differences were related to dissimilar hydrodynamic conditions and diffusion characteristics in the two dissolution testing devices. In situ solid-phase measurement during dissolution testing can largely improve the understanding of the dissolution results of metastable drugs. This information is valuable in drug candidate selection as well as in explaining and controlling the behaviour of drug substances in the final drug products.

KW - dissolution rate

KW - solid state

KW - raman spectroscopy

KW - polymorphism

KW - hydrates/solvates

KW - rotating disc

KW - channel flow cell

KW - simulated gastric fluid

U2 - 10.1016/j.ijpharm.2008.07.001

DO - 10.1016/j.ijpharm.2008.07.001

M3 - Article

VL - 363

SP - 66

EP - 72

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -