Pulmonary Drug Delivery Projects

Investigation of adhesive layer microstructure of adhesive mixtures using Small Angle X-ray Scattering

Ann-Sofie Persson, ResearcherResearch scientist: Ann-Sofie Persson, Researcher
Principal Investigator: Professor Göran Alderborn, Department of Pharmaceutical Biosciences, Uppsala University

Scientific and industrial context. Small Angle X-ray Scattering is a technique whose capacity regarding pharmaceutical powder materials is yet to be completely identified. Within the framework of this project, tests will be conducted to clearify whether it is applicable for measuring inter-particulate pores in powder beds.

Aim. The aim of the project is four-fold with the three initial aims focusing on if small angle x-ray scattering technique can be used to study:

  • Porosity (microstructure) of solid powders
  • Size and shape of inter-particulate pores (voids) in powder beds
  • Adhesive layer microstructure of adhesive mixtures

Outcome. Improved knowledge on how the information of adhesive layer microstructures can be used to understand the dispersibility of adhesive mixtures during inhalation of a pulmonary drug.

Microstructure-Property Relationships of Agglomerates Formed by Dry Granulation

Maryam Tofiq portraitResearch scientist: Maryam Tofiq, MSc
Principal Investigator: Professor Göran Alderborn, Department of Pharmaceutical Biosciences, Uppsala University

Scientific and industrial context. Agglomerates of different types are frequently used in solid formulation, including tablets and dry powder inhalers. Lately, the interest in using dry technologies for the formation of agglomerates has increased substantially, for example to be used in continuous manufacturing. The manufacturing properties of agglomerates are related to their microstructure and to their composition.

Maryam Tofiq research

Aim. The aim of the project is to study the relationship between microstructure and the mechanical and functional properties of agglomerates formed by dry granulation and investigate the effect of composition on such microstructure-property relationships with a special focus on agglomerate plasticity. The aim is further to develop a procedure for the assessment of mechanical properties of agglomerates.

Outcome. A formulation technology platform for rational design of the manufacturing properties of dry granulated particles.

Blend state-blend property relationships of adhesive mixtures for inhalation powders

Research scientist: Anna Simonsson, PhD student
Principal Investigator: Professor Göran Alderborn, Department of Pharmaceutical Biosciences, Uppsala University

Scientific and industrial context. In order to fully utilize the potential of the pulmonary route for local and systemic drug delivery, there is a need to improve our understanding of the formulation of inhalation powders. The pharmaceutics research group at Uppsala University has introduced a blend state theory as a means to systematically investigate and optimize the properties of adhesive blends. The evolution in blend state depends on the combination of carrier and fines and their properties, such as of carrier microstructure, and the mixing process which subsequently affect the performance of the formulation. There is a need to better understand the relationship between blend state and critical properties of adhesive mixtures, such as aerosolization and segregation, as well as to develop validated screening methods by which aerosolization and segregation can be assessed.

Aim. The aim of the project is to investigate effect of carrier morphology on blend state-blend dispersibility relationships. The aim is further to investigate the role of the mixing process for blend state and blend state-blend dispersibility relationships. Finally, the possibility to develop screening methods for assessing dispersibility and segregation will be explored.

Outcome. The outcome of the proposed research is to gain novel information, enabling new strategies on how to formulate adhesive mixtures that are mechanically stable and of high drug load, providing both good manufacturability and dispersibility.

Understanding the compression–decompression cycle for pressure shaping of agglomerates

Marilena Marinaki, doktorand portrattfotoForskare: Marilena Marinaki, PhD student
Ansvarig forskare: Professor Göran Frenning,  Department of Pharmaceutical Biosciences, Uppsala University

Scientific and industrial context. Both compressibility and compactibility of powders are nowadays well understood on a phenomenological level. However, an understanding of the relevance of processes that occur at the particle level is lacking and few, if any, truly mechanistic models of powder compression and compaction exist in the literature. It is here important to consider both the loading and unloading phases of particle/tablet formation to gain a complete understanding of the processes.

Illustration of research project

Aim. The aim of the project is to provide an understanding at the particle scale of the processes that control the structure and properties of granules formed by application and subsequent removal of pressure. The goal is to first develop protocols for analytical powder compression focusing on the unloading stage and secondly to develop contact models and modelling procedures that enable the full loading–unloading cycle to be simulated at the particle scale.

Outcome. It is expected that the project will provide new insights into pressure shaping of granules with special emphasis on refined methods for compression analysis and new methodology for simulation of powder compression at high relative densities.

Understanding the compression–decompression cycle for pressure shaping of agglomerates

Mayura Talwelkar Shimpi, PhDForskare: Mayura Talwelkar Shimpi, PhD
Ansvarig forskare: Professor Göran Frenning,  Department of Pharmaceutical Biosciences, Uppsala University

Scientific and industrial context.  Spray drying is a flexible singe-step technique for the preparation of micron-sized particles suitable for inhalation. With adequate processing parameters and excipients, spray drying is gentle enough to retain the biological activity of peptides, oligonucleotides and other biologics. Spray-dried particles can be used in carrier-free formulations, potentially enabling higher doses of active pharmaceutical ingredients (APIs) to be delivered to the lung.

Aim. To provide a solid scientific understanding of important aspects of spray-dried formulations of inhaled drugs that ultimately will enable enhanced spray-dried formulations to be developed. Of particular interest is to investigate the potential of “novel” excipients for achieving physiochemical stability of a range of API modalities, including small molecules and large biologic molecules.

Completed projects

Particle Dynamics and Multiscale Modelling of Adhesive Mixtures for Inhaled Medicines

Sohan Sarangi portraitResearch Scientist: Sohan Sarangi, MSc
Principal Investigator: Professor Göran Frenning,  Department of Pharmaceutical Biosciences, Uppsala University

Scientific and Industrial Context. Adhesive mixtures in which micronized particles are attached to considerably larger carrier particles, are often used to overcome the cohesiveness resulting from the small particle size needed for pulmonary drug delivery. Formulation and handling of adhesive mixtures is an unexplored regime which is of both scientific and industrial importance.

Aim. The aim of this project is to study the interaction and effective mechanical properties between the drug and carrier particles and their aggregates using a particle based modelling approach and validating the same through experiments.

Outcome. The proposed research is expected to make a significant contribution to the knowledge of adhesive mixtures during general handling and transportation. It would also address generic issue on powder flow and coupling the same with experiments would provide a deeper scientific insight into the problem.

Development of A Novel Pulmonary Controlled Release Drug Delivery System

Ires van der Zwaan portraitResearch scientist: Irès van der Zwaan, MSc
Principal Investigator: Professor Göran Frenning,  Department of Pharmaceutical Biosciences, Uppsala University

Scientific and industrial context. Controlled release formulations for drug delivery to the lung would facilitate new therapeutic opportunities for the inhalation area. However, the area is challenging and there are today no controlled-release formulations available in the market. Lack of these controlled delivery systems limits the development of novel pulmonary therapies.

Irès van der Zwaan research

Aim. The aim of the project is to create new controlled release systems for drug delivery in the lung by surveying and evaluating the dissolution of several promising controlled release options as well as novel systems. Different methods will be used to evaluate existing and novel drug delivery systems such as deposition of inhalation powders using a modified Andersen cascade impactor and dissolution in a Transwell system, a μDiss Profiler and single particle approach.

Outcome. Novel controlled release drug delivery systems for the lungs.

Last modified: 2023-10-30