Porous carbon carriers for amorphous drug delivery

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

Activated carbon as a carrier for amorphous drug delivery:effect of drug characteristics and carrier wettability

Recent research on porous silica materials as drug carriers for amorphous and controlled drug delivery has shown promising results. However, due to contradictory literature reports on toxicity and high costs of production, it is important to explore alternative safe and inexpensive porous carriers. In this study, the potential of activated carbon (AC) as an amorphous drug carrier was investigated using paracetamol (PA) and ibuprofen (IBU) as model drugs. The solution impregnation method was used for drug loading, with loading efficiency determined by UV spectroscopy and drug release kinetics studied using USP II dissolution apparatus. The physical state of the drug in the complex was characterised using differential scanning calorimetry and X-ray diffractions techniques, whilst sites of drug adsorption were studied using Fourier transform infrared spectroscopy and N2 adsorption techniques. In addition, the cytotoxicity of AC on human colon carcinoma (Caco-2) cells was assessed using the MTT assay. Results presented here reveal that, for PA/AC and IBU/AC complexes, the saturation solubility of the drug in the loading solvent appears to have an effect on the drug loading efficiency and the physical state of the drug loaded, whilst drug release kinetics were affected by the wettability of the activated carbon particles. Furthermore, activated carbon microparticles exhibited very low cytotoxicity on Caco-2 cells at the concentrations tested (10–800 μg/mL). This study, therefore, supports the potential of activated carbon as a carrier for amorphous drug delivery

Synthesis of Carbon Onion and Its Application as a Porous Carrier for Amorphous Drug Delivery

Given the great potential of porous carrier-based drug delivery for stabilising the amorphous form of drugs and enhancing dissolution profiles, this work is focussed on the synthesis and application of carbon onion or onion-like carbon (OLC) as a porous carrier for oral amorphous drug delivery, using paracetamol (PA) and ibuprofen (IBU) as model drugs. Annealing of nanodiamonds at 1100 °C produced OLC with a diamond core that exhibited low cytotoxicity on Caco-2 cells. Solution adsorption followed by centrifugation was used for drug loading and results indicated that the initial concentration of drug in the loading solution needs to be kept below 11.5% PA and 20.7% IBU to achieve complete amorphous loading. Also, no chemical interactions between the drug and OLC could be detected, indicating the safety of loading into OLC without changing the chemical nature of the drug. Drug release was complete in the presence of sodium dodecyl sulphate (SDS) and was faster compared to the pure crystalline drug, indicating the potential of OLC as an amorphous drug carrier