Minisymposium: Future formulation strategies

Thursday, January 13, 2011 at 13:00 in the Benzon Auditorium, The Faculty of Pharmaceutical Sciences, University of Copenhagen

Universitetsparken 2, 2100 Copenhagen

Formulation of pharmaceuticals has been - and will remain - a cornerstone of pharmaceutical sciences. This mini-symposium will cover timely topics related to future solutions for individuals working within the formulation field.

Programme

Chairman Professor Jukka Rantanen, The Faculty of Pharmaceutical Sciences, University of Copenhagen

Please click here to see the programme in pdf format. 

This symposium is organized on behalf of the Drug Research Academy by Jukka Rantanen, The Faculty of Pharmaceutical Sciences, University of Copenhagen.

Participation is free of charge and is open for attendance for all interested parties. It is not required to registrate in advance.

Abstracts 

Formulation Considerations for Amorphous Solid Dispersions
(Lynne Taylor, Purdue University, US)

In an era of drug discovery where the number of poorly water soluble compounds is increasing dramatically, formulators are being challenged to develop solubility enhancing formulations. Amorphous solid dispersions are an attractive option since substantial transient increases in solution concentration can be often achieved making them useful for toxicological studies, early phase clinical trials, and in some cases, commercial product. However, their utility is tempered by concerns about conversion of the amorphous drug to the less soluble crystalline form during production, storage and delivery. Of critical importance is the addition of polymers to enhance stability to crystallization. In this presentation, the ability of various polymers to mix with, and inhibit crystallization of active pharmaceutical ingredients will be discussed. The role of the polymer in facilitating the enhanced dissolution of amorphous solid dispersions will also be considered. Finally, the inherent properties of the active pharmaceutical ingredient will be evaluated in terms of the potential success of a solid dispersion formulation approach.  

Strategies in development of oral lipid-based drug delivery systems
(Anette Müllertz, Bioneer:FARMA, Denmark)

Lipid and surfactant -based drug delivery systems (LSBDDS) have proven to increase the oral bioavailability of many poorly soluble drugs, but the mechanisms behind this are still not very well understood. LSBDDS deliver the drug in solution, but in a lipid phase, to the gastro-intestinal (GI) tract. Recently most interest have been given to self-emulsifying drug delivery systems (SMEDDS), that are administered as an isotropic preconcentrate and form nano-emulsions upon dispersion in the GI tract. The main events leading to drug absorption from SMEDDS is then hydrolysis of the lipids in the nano-emulsion particles and transfer of drug to the colloidal phases generated by enzymatic reactions in the GI tract. A rational and strategic development of SMEDDS is dependent on predictive in vitro models, simulating the digestion in the stomach and intestine as well as in vitro absorption. The in vitro tools presently available for development of LSBDDS will be covered as well as their practical application and the in vivo performance of developed LSBDDS.

Nanoparticles for subunit vaccines delivery
(Thomas Rades, Otago University, New Zealand)

With current gene and protein technology it is now possible to identify specific regions of some whole organisms or cells which are likely to be recognized by the immune system, and to reproduce them synthetically as subunit vaccines. These so called epitopes are very safe because they are non-living but they also tend to be only poorly immune stimulating. To improve the immunogenicity of a poorly immunogenic antigen, our approach is to use nanoparticles as delivery systems.  Nanoparticulate delivery systems are thought to enhance the immune response by more closely mimicking a virus or microorganism due to the possibility of multimeric antigen presentation and their large size compared to subunit antigens.

Our group has developed and characterised the following colloidal delivery systems:
* functionalised liposomes (mannosylated or including adjuvants such as Quil A),
* immune stimulating complexes (ISCOMs),
* cationic ISCOMs (termed Pluscoms),
* ISCOM implants,
* polymeric nanoparticles on the basis of microemulsions,
* in situ gelling chitosan solutions containing chitosan nanoparticles,
* cubosomes.

In this presentation I will give an overview about the various nanoparticulate delivery systems our group has developed for the delivery of subunit vaccines. I will describe new results in this field, both on physico-chemical characterisation and immunological activity of these nanosystems.

Visualizing dosage form performance using UV imaging 
(Jesper Østergaard, Faculty of Pharmaceutical Sciences, Denmark)

Current release and dissolution testing technologies rely on the release of the drug substance into a large volume of media followed by measurement of the amount of substance released/dissolved in the bulk phase. From such measurements gross information on release and dissolution rates may be attained, however, extracting information relating the underlying processes of release and dissolution behavior to drug and excipient physicochemical parameters may be difficult. More detailed knowledge on dosage form performance may be attained using recently available UV imaging technology. Proof of concept as to the use of UV imaging for characterization of drug release processes and measurement of local drug concentrations (including surface concentrations) immediately adjacent to a surface (formulation or solid drug) has recently been provided from our lab. The presentation will cover an introduction to UV imaging and illustrate the potential for performing detailed mechanistically oriented release and dissolution studies. Selected examples encompass dissolution imaging of amlodipine besylate solid form transformations and lidocaine surface and single crystal dissolution phenomena, visualization of the release of nicotine from Nicorette® patch samples, and UV imaging of piroxicam diffusion and release from Pluronic F127 hydrogels.