Mini-symposium: Challenges and possibilities of the amorphous state in formulation of pharmaceuticals

Tuesday, August 25, 2009 at 13:00 - 16:00 hrs in Auditorium 4

The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen

Summary:

A thorough understanding of the relationship between physical structures and the properties of an active pharmaceutical ingredient (API) and further, its formulated medicinal product is of critical importance. The amorphous form of an API has in many cases superior performance in comparison with the crystalline counterpart. However, utilizing this aspect in pharmaceutical formulation and building robust processing strategy is challenging. This symposium will highlight both the formulation possibilities and analytical challenges of pharmaceutical high energy solids.

Abstracts:

Introduction to formulation possibilities of amorphous drugs
Thomas Rades Otago University, New Zealand (guest professor at PHARMA, University of Copenhagen)

With the advent of combinatorial chemistry and high throughput screening the number of new chemical entities with low or no water solubility is increasing. If these molecules are also showing insufficient solubility in lipophilic vehicles, amorphisation is a useful means to increase their dissolution rate and solubility, and thus their bioavailability. As the amorphous state is thermodynamically unstable, great care needs to be taken in the development of amorphous forms of drugs. In this talk I will give an overview of the various methods that may be used to develop drugs as amorphous systems and present a fast and material-saving way to come to a formulation decision for amorphous drugs.

Amorphous pharmaceutical solids: characteristics and analytics

Marc Descamps
LDSMM UMR CNRS 8024. Technologic group “Therapeutic materials”
University Lille1 59655 Villeneuve d’Ascq, France

Amorphous pharmaceutical solids (glasses) may provide bioavailability benefits over crystals resulting from better dissolution performance. However amorphous systems are in high energy non-equilibrium states whose physical properties strongly vary with preparation process (e.g. via the melt, a solution or by milling and dehydration) and storage. In this presentation we will give an overview of the current understanding of the nature of glasses and the glass transition, stressing the specificities of molecular mobility (above and below the glass transition), thermodynamics and structure. The main analytical methods for determining these characteristics of glasses will also be reviewed. We will then examine the instability of glass formers and the factors governing crystallization from and ageing of the amorphous state, including a brief discussion on predicting and manipulating the stability of amorphous forms.

Processing of viscous high-energy solids,

Anne Juppo, University of Helsinki, Finland 

Some of the amorphous drugs have glass transition below ambient temperature and thus they are usually difficult to formulate and handle. One reason for this is the reduced viscosity, stickiness, that makes them complicated to handle in unit operations for solid dosage forms. The aim of current study was to develop a new processing method for a sticky amorphous model material. Ultrasound extrusion and cutting were successfully tested to increase the processability of sticky material.

Calorimetry as a tool to characterise amorphous, or partly amorphous, compounds and formulations,

Lars-Erik Briggner, AstraZeneca, Lund, Sweden

Amorphous pharmaceuticals provide big challenges as well as great opportunities within the pharmaceutical industry. Hence, it is of vital importance to characterize, understand and if possible control amorphous or partly amorphous systems. The current presentation describes case studies where one such tool, isothermal microcalorimetry, has been successfully applied during the progression of three different types of formulations.

Please click here to see the programme as pdf-file

This symposium is organised on behalf of Drug Research Academy, PHARMA by professor Jukka Rantanen, PHARMA (jtr(at)farma.ku.dk) and professor Thomas Rades, University of Otago, New Zealand (guest professor at PHARMA)

Participation is free of charge and is open for attendance by all interested parties.