Assessing miscibility of drug-polymer combinations using FBRM
Laura Taramova
Over the summer, before progressing successfully into the third year of my BSc Pharmacology degree at Reading University, I have completed a research project with UROP scheme (Undergraduate Research Opportunities Programme). For the 6-week project I have worked alongside my supervisor, Dr Hisham Al-Obaidi, and his research group at the Chemistry labs.
Figure 1 shows structure of FBRM probe and method of measuring particles.
At the beginning, my research focused on developing and optimising a method for FBRM. FBRM stands for Focused Beam Reflectance Measurement which is a technique used to measure particle size and shape in situ (real time) mainly in pharmaceutical research. FBRM probe structure is shown on Figure 1.
The probe is immersed into media (solution) being tested and functions using an infrared laser beam principle. The laser is directed through a set of modules and focused into a narrow beam at the sapphire window to scan the media for particles swimming past. To ensure good fluid flow (consequently, accurate results), the solution should always be stirred.
After optimising the method, we looked at miscibility of drug-polymer combinations. Miscibility is the ability of liquids to mix and form a homogenous solution. Some drugs can be poorly water-soluble, causing poorer biological effect of the drug on the body. One of the ways to ensure the drug reaches its target is pairing the drug with a hydrophilic carrier.
Figure 2 is a photo of FBRM set up I took at the laboratory.
In our case, we used Progesterone and two potential polymer carriers: hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP). Such hydrophilic carriers can possess adhesive properties, so can stick to mucosal surfaces, consequently delivering the drug to its target site. In a way, polymer and drug form a micelle with polymer on the surface and drug in the centre.
Adding pure progesterone powder to different concentrations of polymer solutions and using FBRM to measure particle count and size, I was able to identify a trend and total particle count in the solutions I tested. These values helped me to distinguish between the two polymers and find out that PVP induced better miscibility as the total particle count was smaller than for HPMC.
Further research could entail testing physical mixtures of progesterone and polymers with dissolution technique, which is the most widely used method of testing tablet’ or capsule’s water solubility.
Figure 3 has Maysaah and I at the top left corner, and Hannah at the centre doing some pipetting.
To summarise, this project not only provided me with considerable laboratory, communication and problem-solving skills, but enabled subtle reconnection with chemistry, which I appreciated as chemistry has been my favourite subject since school. I have mastered using a new tool (FBRM software) from scratch and I have developed a method which I applied to further tests. During the project I also understood the importance of communication and respect within the team as well as ability to work within one. I was lucky to work alongside Dr Al-Obaidi’s research group and two other UROP students (have a look at Figure 3 to catch us at work in the lab!). My supervisor was attentive and supportive, and, of course, very knowledgeable in the field. Apart from the main laboratory skills I have further developed, Dr Al-Obaidi arranged for us to learn and master Raman spectroscopy and Differential Scanning Colorimetry with Dr Rivas-Ruiz, which I enjoyed greatly.
This project gained me invaluable experience and aided in setting a trajectory for my postgraduate career. I am happy to have been selected for this project and thank Reading University and academics for giving undergraduates such career-pivoting opportunities each year.
Reference: Ghezzi, M., Pescina, S., Padula, C., Santi, P., Del Favero, E., Cantù, L. and Nicoli, S. (2021). Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions. Journal of Controlled Release, 332, p.312–336.