Titapiwatanakun, V; (2016) Pharmaceutical applications of CO2 laser irradiation. Doctoral thesis , UCL (University College London).

Abstract

In the pharmaceutical development pipeline, most drugs are poorly soluble; therefore, it is important to tackle this problem by applying novel drug delivery systems or alter the drug substances with either chemical or physical modification such as amorphous formation, co-crystal formation or solid dispersion system to yield better dissolution, absorption and thus therapeutic efficacy. Applying technologies from other fields to develop such systems could be advantageous. Carbon dioxide (CO2) laser irradiation causes rapid melting and vapourization of materials through the absorption of infrared energy from a laser beam. The aim of this work was to investigate the potential pharmaceutical applications of CO2 laser irradiation in several areas including drug delivery systems, drug substances and mixtures of drug and polymer. CO2 laser irradiation was successfully utilized for three main pharmaceutical systems. Firstly, modifying drug release of irradiated enteric coated tablets (Eudragit®L100-55, L30D-55 and HPMCAS-MF) targeting to the duodenum gave rise to both fast and delayed release in pH 5.6 phosphate buffer resembling the duodenum. These changes were caused by pore formation and the change in wettability on the surface of the irradiated coat. Cast films were used to examine the physicochemical and mechanical changes and were shown to have different mechanical properties, contact angles and wettability upon high irradiation. Secondly, a proof-of-concept study of pharmaceutical co-crystal production upon irradiation at certain energy (S50P50) from a mixture of specific stoichiometric ratio of dry powders was presented through rapid melting, sublimation and vapour crystallization. Furthermore, the CO2 laser can induce the physical conversion to amorphous state of the drug-alone system (classic indomethacin) and to many physical states of the various ratios of the drug (paracetamol) and polymer (polyvinylpyrrolidone K 30) mixtures upon rapid heating process. These were clearly confirmed by a range of analytical techniques and physical stability studies. The effect of underlying process settings, namely, laser power, scanning speed, irradiation area, resolution, working distance and scale-up on production were performed.

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