The influence of pressure on the intrinsic dissolution rate of amorphous indomethacin.

Korbinian Löbmann,Danwen Qiu,Theodosia Tsolakou,Wenbo Wang,Thomas Rades,Konstantina Flouda

doi:10.3390/pharmaceutics6030481

Korbinian Löbmann, Danwen Qiu + Show 4 more

Open Access

https://doi.org/10.3390/pharmaceutics6030481

Copy DOI

Journal: Pharmaceutics	Publication Date: Aug 20, 2014
Citations: 40	License type: CC BY 4.0

Affiliation: University of Copenhagen

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.

Highlights

In tablet manufacturing, direct compression is an advanced technique for the development of many drugs into solid dosage forms and its formulation and process variables play a crucial role on the product’s quality [1]
It can be seen that IND can be converted into its amorphous form upon ball milling, either as a pure drug or as a glass solution with PVP
This study showed that compression pressure can influence the intrinsic dissolution rate (IDR) of pure amorphous IND, whereas crystalline IND and a glass solution of IND–PVP were only marginally influenced by different compression pressure

Summary

Introduction

Direct compression is an advanced technique for the development of many drugs into solid dosage forms and its formulation and process variables play a crucial role on the product’s quality [1]. Dissolution rate and solubility of a new drug candidate are crucial factors that influence a drugs’ tendency to supersaturate and its bioavailability. The effect of compression pressure on dissolution rate of solid materials has been reported. Iranloye et al suggested that compression pressure had no influence on the dissolution rate of compressed disks of crystalline salicylic acid, aspirin and mixtures of aspirin and salicylic acid [2]. Velasco et al reported that there is no relationship between compression pressure and the dissolution profiles of diclofenac sodium from matrix tablets [3].

Objectives

Methods

Results

Conclusion