The area of high pressure is receiving great attention and being used to study a range of materials including metals, minerals, energetic materials and pharmaceuticals. Polymers are being increasingly used in pharmaceutical and biomedical applications. The main reason behind this is their physico-chemical characteristics that can be tuned to suit different applications. These characteristics can differ in different forms of the same compound. These forms can be obtained by different techniques including high pressure (Chapter 1).The work presented in this thesis has used high pressure techniques, including diamond anvil cells (DACs) and large volume press cell, to investigate pharmaceutical polymers and a model active pharmaceutical ingredient (ibuprofen). The change of materials under pressure was studied by in-situ Raman spectroscopy (Chapter 2). The first challenge faced in this project was fluorescence, which hinders Raman spectroscopy.Surface enhanced Raman spectroscopy (SERS) technique was adopted to improve the signal and overcome fluorescence. This was achieved successfully on weak Raman scattering amino acids and fluorescent polymers (Chapter 3). A range of commonly used polymers were studied under high pressure in DAC. Poly glycolic acid (PGA) and poly lactic acid (PLA) exhibited a similar phenomenon of moving from crystalline or semi-crystalline into a less ordered form between 4-5 GPa. Ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC) demonstrated a similar change at about 2-3 GPa (Chapter 4).Both EC and HPMC were used as a platform for sustained release dosage forms in different ratios with ibuprofen. These formulations were mixed using resonant acoustic mixing technique and subjected to high pressure (0.8 GPa) before being tested for drug release. The change in release patterns was mainly caused by the pressure transmitting medium (PTM) rather than the application of pressure (Chapter 5). Individual formulation components were used as received powders, treated by PTM at ambient pressure and subjected to 0.8 GPa before exploring their flowability.The PTM treatment and pressure has increased the flow function of polymers but not ibuprofen. The formulation blends were tested for flowability in powder and ambient pressure forms. Unlike individual components, the treated blends exhibited a decrease in flow function and increase in cohesion (Chapter 6).Overall, this thesis demonstrates that the application of pressure, using DACs, on commonly used polymers in pharmaceutical applications does help in inducing phase transitions at different pressures. Adapting SERS technique has been successful in overcoming fluorescence in polymers and improving Raman signal in weakly scattering amino acids. The application of pressure, using large volume press, did not have a significant effect on release pattern of APIs from the tested formulations.The change was mainly due to the pressure transmitting medium. The effect of pressure was tested on powder flowability and found to increase polymers flowability but not ibuprofen.
|Date of Award||4 Jul 2019|
- University Of Strathclyde
|Supervisor||Iain Oswald (Supervisor) & Alexander Mullen (Supervisor)|