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H. M. Fadda, S. Gaisford, Q. Ru, P. T. Khaw, S. Brocchini; Understanding Changes in the Solid Phase Properties of Tissue Tablets on Exposure to Aqueous Media. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5311.
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© ARVO (1962-2015); The Authors (2016-present)
The matrix metalloproteinase inhibitor, ilomastat, was incorporated into a prolonged release tissue tablet for use in the subconjunctival space following glaucoma filtration surgery (GFS). Significantly better bleb functionality was maintained with this tablet in a clinically validated in vivo model when compared to mitomycin C (ARVO2008 #4538). It is necessary to determine physical properties of this tablet and to determine their changes while implanted in the bleb. We have now elucidated some of these properties before and after aqueous incubation of the tablet.
Ilomastat tissue tablets were fabricated by direct compression. Differential scanning calorimetry (DSC) was used to determine the solid phase properties of ilomastat in the powder and tablet form before and after 48 h exposure to phosphate buffer in a flow chamber at 37°C. DSC Q2000 (TA instruments, Delaware, USA) was used in modulation mode with an underlying scan rate of 2°C/min, modulation amplitude 1°C/min and modulation period of 60 sec. Fast-scan DSC (RHC, TA instruments) was also used at a heating rate of 400°C/min. Dynamic vapour sorption (DVS, SMS Ltd) was used to assess the moisture uptake of the ilomastat tablet at 90% relative humidity (RH) at 32°C until equilibrium was reached.
DSC showed ilomastat powder and tablet to exist predominantly in a crystalline form. Melting was observed at 208°C. Incorporating ilomastat into a tablet does not change the crystal properties of the drug. An endothermic, thermodynamic and kinetically reversible solid-solid transition was observed at 122°C. This observation is consistent with there being two enantiotropic polymorphic forms. The moisture uptake of the ilomastat tablet, by DVS, was 4.7% at 90% RH; all moisture absorbed was displaced at 0% RH conditions. On exposure of the tablet to an aqueous environment for 48 hours, a change in physical form of ilomastat arose with a depression of melting point to 183°C. The solid-solid transition was still observed at 122°C.
Ilomastat used in our tissue tablets exists in the crystalline form. A change in the crystal habits of ilomastat was observed on exposure to aqueous media. While these tablets maintain bleb function, there is a need to understand their physical properties during exposure to an aqueous environment.
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