Engineering Biomaterials using Quality by Design for the delivery of Ibuprofen for use in Cardiovascular therapy

Cardiovascular disease is the leading cause of death worldwide representing 32% of global deaths in 2019 alone. This percentage has been steadily rising. Pharmaceutically, many strategies have been implemented worldwide to help fight the consequences of this disease, such as polymer heart patches and pacemakers. Treatment of damaged tissue may involve the delivery of Non-steroidal anti-inflammatory (NSAIDS) medicines to target damaged areas. However, challenges arise as these medications present as poorly water-soluble, limiting the options available for treatment of the damaged tissue. Strategies such as spray drying, solvent evaporation and encapsulation of these drugs have been previously implemented to overcome present limitations. In this thesis, Ibuprofen drug was loaded into two types of mesoporous silica (MCM-48 and MCM-41) via Electrohydrodynamic atomisation (EHDA). The Quality by Design (QBD) process was carried out prior to loading in order to identify optimum parameters (flow rate, voltage, distance from the needle to the platform) in the EHDA technique. All formulations were found to hold ideal viscosity, surface tension and electrical conductivity values and were then carried out to investigate the effect of the technique on the physicochemical properties (entrapment efficiency, uniformity of morphology and size, permeability, dissolution, crystallinity and thermal behavior) of the particles produced. It was found that uniform morphology and size of the silica particles were obtained at a flow rate range of 30-35 µm/min and a voltage range of 18-23(KV) Following this, these ibuprofen loaded mesoporous silica particles were then encapsulated in PLGA using the coaxial EHDA method with an aim to sustain the release of the drug from the pores of the silixa. It was concluded from TGA and XRD analysis that the ibuprofen drug was successfully encapsulated in a complete amorphous form into the mesoporous silica pores via XRD analysis. It was found that using EHDA resulted in dissolution rates 3.8 folds higher compared to the raw crystalline form of the drug, taking the original 17% release in 24 hours to a maximum of 73% in 24 hours. It was also concluded that the encapsulation in PLGA resulted in a 2 fold dissolution in comparison to the loaded mesoporous silica alone, resulting in a maximum of around 50% in 24 hours. QBD was then used a second time to identify optimum parameters in the formulation of PVA-PVP-GLY polymer films. The physicochemical properties were then investigated as in previous chapters. It was found that the films presented excellent flexibility, uniform topography, and ideal swelling properties. Furthermore, both the tensile strength and contact angle results demonstrate an ideal film for use in drug delivery.
Finally, these encapsulated particles previously created were then loaded onto these films using single needle EHDA at the optimum ranges identified previously and their physicochemical properties were them investigated again in order to see if desirable results had been met. These included XRD, DSC, Tensile strength, flexibility, TGA,FTIR and Invitro drug release. It was concluded that successful loading of the encapsulated loaded silica onto the polymer film had taken place via EHDA. Furthermore, an amorphous state was maintained for both the film and the encapsulated ibuprofen loaded silica particles. This was confirmed using multiple characterization methods such as XRD, DSC and TGA. This displays the potential of this drug delivery system in tissue regeneration and targeted drug delivery treatments.