Purchase this article with an account.
Abeer Mohamed Ahmed, Alastair Lockwood, Sahar Awwad, Garima Sharma, Peng T. Khaw, Steve Brocchini; Cellulose Based Tablet For Sustained Release Of Ilomastat. Invest. Ophthalmol. Vis. Sci. 2012;53(14):502.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Ilomastat is a matrix metalloproteinase inhibitor (MMPi) that has been shown to inhibit fibrosis after glaucoma filtration surgery in a rabbit model of ocular fibrosis. To reduce scarring and fibrosis following glaucoma surgery and to avoid dose dumping when injected, a sustained dosage form is required that allows a prolonged local concentration of ilomastat to be maintained within the subconjunctival space. Cellulose based excipients such as carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC), which have been used in ocular medicine were used to fabricate a small tablet for subconjunctival implantation.
Ilomastat (1.0 mg) was dispersed in water (1.0 mL) and sonicated for 30 min to produce a homogenous suspension. An aqueous solution of CMC (2.0%) or HPMC (2.0%) was prepared by dissolving the desired amount of the polymer in water overnight. The suspension of ilomastat was then added to the aqueous polymer solution (2%, 200.0 µL) and homogenized using Ultra-Turrax homogenizer for 2.0 min. The mixture was freeze dried. The lyophilised powder was pressed into a tablet using 3 mm punch and die. The release of ilomastat from the tablet in phosphate buffered saline (PH 7.4) was determined at flow rate of 2.0 µL at 35.0 °C in a flow rig. The concentration of the released ilomastat was measured using high performance liquid chromatography at 280 nm.
Ilomastat was successfully fabricated into a tablet that contains a dispersion of a crystalline form of ilomastat in a cellulose based polymer matrix. The weight of the tablet was in the range of 4.5-6.5 mg. Fabrication of the ilomastat tablet using cellulose derivatives (CMC and HPMC) resulted in a sustained release of ilomastat over 10 days. The tablets were prepared using CMC (2.0%), HPMC (2.0 %) and a mixture of CMC/HPMC (1:1). The release profile of ilomastat was 71.8, 52.9 and 66.3 % respectively after 242.8 h (10 days). The concentration of the released ilomastat was in the range of 44.7-200.2 (CMC), 11.8-193.6 (HPMC) and 48.3-162.3 µM (CMC/HPMC 1:1) over a period of 10 days, which was within the therapeutic range (10-100 µM).
Sustained release of ilomastat was achieved by its fabrication into a cellulose based tablet. The release period is prolonged, which may be suitable for a successful sub-conjunctiva implant for improvement of the outcome of glaucoma filtration surgery.
This PDF is available to Subscribers Only