Pharmaceutical Technology

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Description

The ambition of the research group in Pharmaceutical Technology is to conduct methodological and basic mechanistic research that can contribute to the development of better and more cost effective pharmaceuticals. We will develop firstly, new and improved drug delivery solutions and secondly, formulation tools for a more effective development and manufacturing of drug products. The core expertise of the group is powder science and technology which is a scientific discipline with applications to different type of products, including pharmaceuticals. An important and common research question for the research projects of the group is how critical properties of particles and particle systems can be assessed, controlled and predicted. The main applications of the research are formulation of medicines for peroral and pulmonary administration. Three research projects are currently developed within the group, i.e.: (1) Analytical powder compression; (2) Formulation of dry granulated powders; (3) Formulation of inhalation powders. The research is part of the research program of the Swedish Drug Delivery Center (SweDeliver).

Labbmaskin

Analytical powder compression

Tablets are typically fabricated by confined powder compression using tablet tooling of different types. Due to the application of force by the tableting punches, the volume of the powder held in the die is reduced until at coherent tablet of required fracture strength, attrition resistance and porosity is formed. Mechanical strength is hence a fundamental quality attribute of tablets and the ability of the powder to cohere into a tablet must be controlled. The powder compression event involves a series of physical phenomena on the particle level which are expressed during a short period of time. Particles constituting the powder are typically of varying size, shape and porosity and are hence difficult to reproducibly characterize as single particles. An alternative is to derive particle properties from powder compression data and the term analytical powder compression has been coined for such an approach. Analytical powder compression (APC) is defined as the determination of compression parameters as firstly, indications of the mechanical and friction properties of particles and secondly, as predictors of the ability of the powder to form tablets. The research group has developed a protocol for APC and is now further developing this protocol in terms of the assessment of elastic particle properties and the prediction of powder tabletability and compactibility.

Formulation of dry granulated powders

Poorly soluble drugs, such a BCS class II drugs, are typically used in drug products as micronized particles. In order to enable tablet manufacturing of such fine particulate material, the particles are often pre-processed by a size enlargement process during which a granular powder is prepared which consists of granules considerably larger than the starting material. An emerging granulation technology for large scale tablet manufacturing is dry granulation by roll compaction, a technology suitable for continuous manufacturing. The research group studies how physical and technical properties of the granules are affected by variations in powder composition and process parameters. The aim is to derive a mechanistic understanding of the compression properties of the granules enabling a rational approach to their formulation. The approach used in these studies is the sequential relationship composition – microstructure – single granule mechanics - tableting performance. Both traditional granules and model granules of uniform size and shape are used in research.

Formulation of inhalation powders

Different types of dosage forms are used to deliver drugs to the lung och among these, inhalations powders are common due to their patient friendly properties. In order for particles to be inhalable and be deposited in the lung, they have to be very fine with an aerodynamic particle diameter typically below 5 mm. To enable automated machine filling of the inhaler as well as emptying of the inhaler and subsequent particle aerosolization during use, the micronized particles usually have to be agglomerated. Examples of two different types of agglomerates used in drug products, which hence represents important formulation technologies for inhalation powders, are adhesive mixtures (structured agglomerates) and soft non-structured agglomerates. In the research group, physical and formulation properties of agglomerates for inhalation are studied, primarily adhesive mixtures. A classification system, denoted a blend state theory, of adhesive mixtures has been introduced and the impact of blend state on powder physico-technical and aerosolisation properties has been demonstrated for different carriers and drugs. With this conceptual description as starting position work is on-going how the blend state can be controlled as well as the possibility to affect the interparticulate forces acting in the blend.

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