Mohmad Sabere, ASB; (2016) Formulation and characterisation of conventional and 3-D printed mini-tablets and inserts for ocular use. Doctoral thesis , UCL (University College London).

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Abstract

This thesis describes a study into the formulation, manufacture and characterisation of mini-tablets and inserts for ocular use. Powder-based mini-tablets were formulated using the antibiotic chloramphenicol and a range of polymers. The effect of powder particle size on the quality of the products was investigated and was significant only for drug release from polyethylene oxide 8M mini-tablets. Transition temperature microscopy was used to assess drug distribution across the surface of the mini-tablets. Good contact of the nano-probe with the mini-tablet surface was the determining factor in the quality of the images created, with the residual particle shape after compaction playing a significant role. A novel approach to the manufacture of mini-tablets using 3-D printing was investigated. The fused deposition modelling approach was unsuccessful due to the difficulty in producing extrudates of the required polymers. Stereolithography was used to prepare a range of formulations, with polyethylene glycol (PEG) diacrylate as the base material and phenylbis (2,4,6-trimethylbenzoyl) phosphine oxide as photoinitiator. The quality of the 3-D printed tablets was variable and dependent on the relative content of these two ingredients and the equipment settings. The 3-D printed mini-tablets showed a slow first-order drug release profile, which was increased by the inclusion of pore formers such as low molecular weight PEG. The applicability of the stereolithography approach for 3-D printing of individualised ocular inserts was investigated. A cranial MRI scan of an adult male human was used, with permission, to generate a 3-D image of the eye, from which a personalised ocular insert was produced. A matching personalised flow-through dissolution chamber was constructed, in order to enable to assess the drug release profile from the inserts. Similarly to the 3-D printed mini-tablets, the drug release followed a slow first-order profile, and was increased by the presence of pore formers in the insert.

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