Title

Development and critical evaluation of solvent-free photocured coatings for pharmaceutical application

Date of Completion

January 1994

Keywords

Chemistry, Pharmaceutical|Chemistry, Polymer|Health Sciences, Pharmacy

Degree

Ph.D.

Abstract

Four siloxane prepolymers (I, II, III and IV) were used to understand the photocuring mechanism and to test the feasibility of photocuring as a potential pharmaceutical coating technique. IV was pre-formulated to contain a hydroxy ketone initiator and a thiol crosslinker, while photocurable I, II and III were prepared by dissolving benzoin methyl ether (BME) in corresponding prepolymers. Degree of photocuring and Tg of a photocured film was measured using real time FTIR and DMTA, respectively. The photocurable I (0.05% BME) achieved 82% polymer conversion at 25$\sp\circ$C under N$\sb2$ and formed networks with 37$\sp\circ$C Tg, as contrast to 63% conversion and 50$\sp\circ$C Tg when 0.5% BME used. The different levels of BME apparently caused the change of crosslinking densities in photocured-I films. The polymer conversions of III and IV were 60%, and 100%, respectively, with corresponding Tgs at 20-60 and $-$1140C. II did not form solid films after 40% polymer conversion attained. A diffusion rate limited polymerization was believed to cause the polymer conversion inversely related to the Tgs of the photocured films. Further studies showed that photocured IV films (TiO$\sb2$ filled and unfilled) were not permeable to ionic species, but rather to salicylic acid at pH 1.2 and 7.4 through partition-diffusion principle. The filled and unfilled photocured IV films had water vapor transmission constants 1.03 and 1.13 g/cm$\cdot$hr$\cdot$mmHg, respectively. IV was also applied to coat 14-18 mesh nonpareil beads in a pan coater using photo-irradiation. The resulting coatings were approximately 50$\mu$m in thickness. The coated bead-aggregation was not a function of coating layers for both filled and unfilled IV coatings, but rather of the irradiation time. Three minutes of irradiation per layer of filled coating and six minutes irradiation per layer of unfilled coatings generated the lowest aggregation among 1, 3 and 6 minutes per layer irradiation schedules in corresponding filled and unfilled coatings. Coating integrity, as measured with marker dye release profile, showed an inverse relationship to the corresponding bead aggregation which supported the hypothesis of a swelling stress induced coating breakage during the release studies. ^