Purpose:
Evaluate a hydrophobic biodegradable polysaccharide device capable of delivering pharmaceutical agents in a controlled manner in an in vitro model.
Methods:
Biodegradable devices comprised of a hydrophobically modified polysaccharide (h-PS), 40-50% w/w; polyethylene glycol (PEG), 20 kD average molecular weight, 0-10%; and triamcinolone acetonide (TA), 50% w/w; were fabricated by a solventless extrusion process. Materials were fed in dry powder or pellet form to an extruder which uniformly mixed the components at a temperature sufficient to melt the polymeric materials but not the TA. The resulting mixture was forced through a heated die and elongated into a 500 micrometer diameter cylindrical shape. The cooled extrudate was cut to 5 millimeter lengths to form devices with a total mass of 1 mg.Elution of the TA was determined by repeated exchanges of 4 ml phosphate buffered saline, pH 7.4, agitated and maintained at 37oC, at appropriate time intervals. Concentration of TA at each time point was quantified by UV-vis spectroscopy. Content and purity of TA in devices was determined by extracting TA with tetrahydrofuran and assaying via HPLC. Solid form of TA was confirmed by X-ray powder diffraction.
Results:
Tunability of TA elution rate from 0.1 to 5.0 µg/day was demonstrated by varying device formulation. See Figure 1. 95-105% of the TA was recovered from assayed devices and the impurities profile was unchanged. Crystalline polymorphic form of the TA was not altered. Devices were implanted into cadaveric porcine eyes via a minimally invasive technique, and were found to have appropriate mechanical integrity.
Conclusions:
A device has been developed that provides controlled release of TA. Extrapolation of elution data predicts release will last longer than 1 year in some cases. The device may be fabricated into a shape and size suitable for minimally invasive implantation into the vitreous space.
Keywords: vitreous • corticosteroids • injection