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Saja Muwaffak, Peng Tee Khaw, Richard A Eiferman, Steve Brocchini, Dale P DeVore; An Injectable Collagen Depot for Subconjunctival Drug delivery. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3354.
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© ARVO (1962-2015); The Authors (2016-present)
Long acting injectable formulations of anti-scarring agents are needed to treat subconjunctival fibrosis. An in-situ polymerisable collagen (IPC) is being developed as an injectable depot for subconjunctival drug delivery. Pirfenidone (water soluble) and illomastat (poorly water soluble) were evaluated to determine their effects on collagen gelling and drug release profiles.
The IPC was prepared by gradually increasing the pH of collagen to pH 7 in the presence of ethylenediaminetetraacetic acid. The formulations were then prepared using both drugs and the drug release was then carried out at 37 °C within a flow model (2 µL/min) for 14 days.Dynamic mechanical analysis was conducted to characterise the mechanical stiffness of the gel formulations. The effect of freeze drying on the gel properties in formulation was investigated.
Gelling was characterised by fibril formation which began within a few seconds after contact of the IPC solution with biologically relevant media (e.g. PBS) at 37 °C.As seen in Figure 1, the ilomastat formulation showed a slow-release profile (at 10 mg/mL) where the drug release occurred over 14 days. The more water soluble pirfenidone formulation released all the drug in 3 days. In the case of ilomastat, the formation of a micro-precipitate (less than 100 µm) and precipitate entrapment inside the gel may have caused the slower dissolution process.The mechanical stiffness of the IPC gel before drug loading was approximately 1.2 kPa which was reduced by 25% after the formulation process. Furthermore, there was no significant difference in the mechanical stiffness of the formulation after extrusion with a 30G needle, compared to prior to extrusion. Furthermore, the time for gelling and the gelling properties were not affected by freeze drying.
IPC has the potential to deliver poorly-soluble drugs such as illomastat due to their precipitation inside the gel. Therefore, the IPC can be a useful vehicle for powdered formulations of drugs. Drug precipitation within the IPC results in a slow-release drug profile which could be beneficial for conditions such as subconjunctival fibrosis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Figure 1. The dissolution profile of the ilomastat and pirfenidone formulation.
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