Porous carbon carriers for amorphous drug delivery

Abstract

Given the great potential of porous carrier based drug delivery for stabilising the amorphous form of drugs and enhancing dissolution profiles, this thesis centred on investigations into the application of activated carbon (AC) and carbon onion (OLC) as porous carriers for oral delivery, using paracetamol (PA) and ibuprofen (IBU) as model drugs. Initial work was focussed on the toxicity studies of AC followed by preparation and characterisation of drug/AC complex. Results showed that AC is a promising drug carrier with low toxicity, high loading capacity and ability to stabilise amorphous drug. However, loading efficiency and solid state characteristics were different for PA and IBU, whilst the drug release from AC was incomplete in the absence of surfactant. To investigate the factors affecting drug loading, three different loading methods were compared, with solution adsorption followed by centrifugation found to be the optimum method to achieve maximum loading with least crystallinity. Initial drug concentration in the loading solution was also found to influence the loading, where the optimum concentration to achieve maximum loading without any crystallinity differed depending on the chemical nature of the drug. Further, the surface chemistry of AC was modified in order to achieve complete drug release, and results showed that drug release increased with an increase in the surface oxygen content of AC. Also, drug release was found to increase with a decrease in the micropore volume fraction. The second part of the work was focussed on the synthesis and characterisation of OLC, followed by drug loading studies. Results showed that annealing of nano-diamonds (ND) at 1100 ºC produced OLC with a diamond core, which is non-toxic. Drug loading studies revealed that loadings achieved were lower than those seen with AC, regardless of drug solubility. Of the both carriers investigated, AC was less expensive and found to be a promising carrier with higher loading capacity and lower toxicity.