Next Article in Journal
Bioadhesive Mini-Tablets for Vaginal Drug Delivery
Previous Article in Journal
Temperature Dependence of the Complexation Mechanism of Celecoxib and Hydroxyl-β-cyclodextrin in Aqueous Solution
Article Menu

Export Article

Open AccessArticle
Pharmaceutics 2014, 6(3), 481-493; doi:10.3390/pharmaceutics6030481

The Influence of Pressure on the Intrinsic Dissolution Rate of Amorphous Indomethacin

Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark
*
Author to whom correspondence should be addressed.
Received: 7 July 2014 / Revised: 5 August 2014 / Accepted: 7 August 2014 / Published: 20 August 2014
View Full-Text   |   Download PDF [1167 KB, uploaded 20 August 2014]   |  

Abstract

New drug candidates increasingly tend to be poorly water soluble. One approach to increase their solubility is to convert the crystalline form of a drug into the amorphous form. Intrinsic dissolution testing is an efficient standard method to determine the intrinsic dissolution rate (IDR) of a drug and to test the potential dissolution advantage of the amorphous form. However, neither the United States Pharmacopeia (USP) nor the European Pharmacopeia (Ph.Eur) state specific limitations for the compression pressure in order to obtain compacts for the IDR determination. In this study, the influence of different compression pressures on the IDR was determined from powder compacts of amorphous (ball-milling) indomethacin (IND), a glass solution of IND and poly(vinylpyrrolidone) (PVP) and crystalline IND. Solid state properties were analyzed with X-ray powder diffraction (XRPD) and the final compacts were visually observed to study the effects of compaction pressure on their surface properties. It was found that there is no significant correlation between IDR and compression pressure for crystalline IND and IND–PVP. This was in line with the observation of similar surface properties of the compacts. However, compression pressure had an impact on the IDR of pure amorphous IND compacts. Above a critical compression pressure, amorphous particles sintered to form a single compact with dissolution properties similar to quench-cooled disc and crystalline IND compacts. In such a case, the apparent dissolution advantage of the amorphous form might be underestimated. It is thus suggested that for a reasonable interpretation of the IDR, surface properties of the different analyzed samples should be investigated and for amorphous samples the IDR should be measured also as a function of the compression pressure used to prepare the solid sample for IDR testing. View Full-Text
Keywords: amorphous; crystalline; dissolution; compression pressure; indomethacin amorphous; crystalline; dissolution; compression pressure; indomethacin
Figures

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Löbmann, K.; Flouda, K.; Qiu, D.; Tsolakou, T.; Wang, W.; Rades, T. The Influence of Pressure on the Intrinsic Dissolution Rate of Amorphous Indomethacin. Pharmaceutics 2014, 6, 481-493.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Pharmaceutics EISSN 1999-4923 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top