Mingshi Yang
Lektor
E-mail: my(at)farma.ku.dk
Telefon: 35 33 61 41
Rum 13 – 712

Solid dispersions to improve oral bioavailability of poorly water-soluble drugs
Most of the new chemical entities (NCEs) under development nowadays are poorly water soluble drugs, which usually possess poor oral bioavailability. As one of the most promising strategies to improve the oral bioavailability of poorly water-soluble drugs, solid dispersion are mainly obtained by two major different methods, i.e. melt-quenching and solvent evaporation. To date many research have been focused on new manufacturing processes to obtain solid dispersions but little work has been done to investigate the effect of particle characteristics on subsequent processes, such as mixing, dry granulation, compression and subsequently the quality attributes of the end final product.
Hence this project is aimed to get insight into the impact of processing parameters on the final product characteristics. In this project the students will have the chance to work on design of solid dispersions using spray drying; compression of direct compressible granules using Texture analyzer and mini-tablet machine; solid state characterization using SEM, DSC, XRPD, Raman, NIR and FTIR; dissolution test using HPLC method. The students will also have chances to practice Process Analytical Techniques (PAT) in combination with multivariate data analysis to do on line monitoring of the product during e.g. blending, dry granulation and tabletting.
Supervisors: Mingshi Yang, Jari Pekka Pajander, Jørn Møller-Sonnergaard'

Particle design via spray drying process
The spray drying process is one of the most commonly used techniques in pharmaceutical industry for purposes such as drying of thermally-sensitive materials, improving physical property of powder and microencapsulation. Nowadays it is also widely used to design drug delivery systems such as polymeric microspheres, bioadhasive microparticles and nanocomposite particles for pulmonary delivery. To design desirable functional particles it is critical to understand and control particle formation during the spray drying process. In this project various experimental techniques such as single droplet drying acoustic levitator will be employed to investigate the droplet drying and particle formation. The students will also have a possibility to use spray drier, scanning electron microscropy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Raman Spectroscopy, and Near infrared (NIR) spectroscopy. This project will be in collaboration with Niro GEA A/S and Prof. Chan in University of Sydney.
Supervisor: Mingshi Yang

Influence of polymeric excipients on the outcome of spray-drying
Spray-drying technology has shown beneficial effects on enhancing the bioavailability of poorly water-soluble drugs as well as stabilizing pharmaceutical protein formulations. During spray-drying the substances undergo a quick drying, and the outcome of the process will be influenced by both formulation composition and process variables. The aim of this project is to study how the chemical and physicochemical properties of the polymeric excipients in combination with process variables influence the particle characteristics, product attributes and stability of the product. The physicochemical properties of the polymeric excipients will be analyzed with rheological technique and surface analytical tools. The formulation will be processed using spray-dryer. Methods used to characterize particle properties and chemical interactions are SEM, lasser diffraction, XRPD, DSC, Raman, and IR.
Supervisors: Stefania Baldursdottir and Mingshi Yang 

Spray drying of protein formulation
Spray drying process may result in a dry powder with a crystalline matter or amorphous matter, or a mixture of these two. For biomacromolecule - such as proteins - a viscous amorphous state may be more desired in terms of retaining conformational integrity of proteins during the spray drying process. However, the crystalline form is more prefered for a powder in respect to storage stability of the powder, since amorphous form is metastable. It is important to understand the interplay of the different solid-state forms, the stability of protein as well as the physical properties of particles. In this project the students will have possibility to use spray drier, scanning electron microscropy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Raman Spectroscopy, Fourier transform infrared spectroscopy (FTIR), High performance liquid chromatography (HPLC). Supervisors: Mingshi Yang in collaboration with Marco van de Weert (Biomacromolecular drug delivery)

Advanced delivery of poorly-water soluble drugs by solid lipid micro/nano-particle system
Solid lipid micro/nano-particles are made of a mixture of solid and/or liquid lipids. They may increase the solubility and dissolution rate of poorly water-soluble drugs (PWD) in vivo by either increasing the specific surface area of PWD or by stabilizing an amorphous or molecular form of drug molecules. The aim of the project is to design and optimize solid lipid micro/nano-particles as stable carriers to improve the bioavailability of poorly water soluble drugs through oral administration, to investigate how the interaction of lipid particles with other components in the gastrointestinal tract affects drug release profile, and to achieve controlled drug release by modifying the physiochemical properties of lipid particles.
Solid lipid micro/nano-particles with selected excipients will be produced by using diverse pharmaceutical technologies such as spray drying, solvent evaporation method and O/W melt dispersion techniques. The solid lipid micro/nano-particles will be characterized by size distribution, morphology, solid state analysis, lipid state and loading efficiency using SEM, DSC, XRPD, Raman, IR and TOF-SIMS. The stability of lipid particles and drug release profile will be investigated by using the established in vitro lipolysis model, which simulates the events taking place in the GI tract during digestion. The interaction of solid lipid particles with other components in the GI tract will be examined by analyzing lipolytical products using HPLC.
Supervisors: Huiling Mu and Mingshi Yang