An Experimental and Computational Study of the Effect of Bioceramic Porosity on Drug Release Kinetics
1 online resource (129 pages) : PDF
University of North Carolina at Charlotte
Porous bioceramics have been explored for drug delivery applications. The goal is to design a material that can provide controlled release of therapeutic doses of the drug for a duration long enough to cause complete healing. For drug carriers, the parameters of importance are the drug release rate, cumulative drug release (CDR) and duration of release. These parameters are largely dependent on the porosity characteristics. In the present study, porous α-Cristobalite disks with different porosities are studied as carriers of the drug Vancomycin. The studies comprise of both experiments and simulations.The experimental work focused on preparation of α-Cristobalite disks followed by a study of the drug binding and release kinetics. α-Cristobalite particles in the size range of 38-90 µm were mixed with 15%, 30% and 45% by mass of Poly-Ethylene Glycol (PEG). The Cris-PEG mixtures were pressed at 283 MPa, heat treated at 100 °C/1 hr and 350 °C/24 hr and sintered at 1150 °C for 24 hours to obtain porous disks with different porosity characteristics. The disks were immersed in Vancomycin solution (8 mg/ml) for 16 hours at room temperature. The amount of drug absorbed by the disks was measured using Gravimetric analysis. The amount of drug adsorbed on the disk surface was calculated using HPLC analysis. For the analysis of drug release kinetics, the disks were immersed separately in 3 ml of PBS in polystyrene jars and incubated at 37 °C on an orbital shaker. After 1 hr, 4 hrs, 8 hrs, 16 hrs, 24 hrs and every 48 hrs thereafter, 1 ml of the solution was withdrawn and stored and replenished by the same volume of fresh PBS. The concentrations of Vancomycin in the collected samples were measured to calculate the CDR over time. Also, SEM analysis of Cris-PEG disk sections was performed to quantitatively and qualitatively study the surface morphology and pore size distribution of the disks.The purpose of the computational work was to study the significance of various mechanisms that drive the diffusion of drug from the ceramic disks and provide insights into the use of computational tools in developing ideal drug delivery vehicles. Drug release process from the disks involves two main phases: Burst Release phase, in which there is a dissolution of the adsorbed layer of drug on the disk surface into the physiological solution and the Sustained Release phase, in which there is diffusion of drug through the internal pores of the disks into the physiological solution. These two mechanisms are modeled using the Fickian Theory of Diffusion and the Finite Element Method. Axisymmetric finite element models of the disk and the PBS region were developed and solved using the FEM package ABAQUS and the results were post-processed by MATLAB to compute the CDR. Two quantities, Diffusion Coefficient and Mass-Transfer Coefficient, are essential for these models. These were obtained by matching the computational and experimental values of CDR.Relation between the drug release kinetics and the Pore Size distribution was also studied to identify the pore size categories which control the release kinetics.
Cherukuri, HarishEl-Ghannam, Ahmed
Thesis (M.S.)--University of North Carolina at Charlotte, 2016.
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