Effect of PF-04217329 a prodrug of a selective prostaglandin EP(2) agonist on intraocular pressure in preclinical models of glaucoma.

Better control of intraocular pressure (IOP) is the most effective way to preserve visual field function in glaucomatous patients. While prostaglandin FP analogs are leading the therapeutic intervention for glaucoma, new target classes also are being identified with new lead compounds being developed for IOP reduction. One target class currently being investigated includes the prostaglandin EP receptor agonists.

L-Carnosine: multifunctional dipeptide buffer for sustained-duration topical ophthalmic formulations.

Objectives: The use of l-carnosine as an excipient in topical ophthalmic formulations containing gellan gum, a carbohydrate polymer with in-situ gelling properties upon mixing with mammalian tear fluid, was developed as a novel platform to extend precorneal duration. Specific utilisation of l-carnosine as a buffer in gellan gum carrying vehicles was characterised.

Methods: Buffer capacity was evaluated using 7.

Ocular pharmacokinetics and hypotensive activity of PF-04475270, an EP4 prostaglandin agonist in preclinical models.

Prostaglandins are widely used to lower intraocular pressure (IOP) as part of the treatment regimen for glaucoma. While FP and EP2 agonists are known to lower IOP, we investigated the ocular hypotensive activity and ocular drug distribution of PF-04475270, a novel EP4 agonist following topical administration in normotensive Beagle dogs. PF-04475270 is a prodrug of CP-734432, which stimulated cAMP formation in HEK293 cells expressing EP4 receptor and beta-lactamase activity in human EP4 expressing CHO cells transfected with a cAMP response element (CRE) with an EC(50) of 1 nM.

The impact of low levels of amorphous material (<5%) on the blending characteristics of a direct compression formulation.

During the manufacture of tablets for registration stability studies, it was observed that blends manufactured using milled active frequently failed the blend content uniformity criteria (actual relative standard deviation (RSD) of 4-15%) at the prelubrication stage, whereas unmilled active batches were consistently giving very good blend uniformity results (RSD<3.5%). The addition of magnesium stearate dramatically improved the blending characteristics of the milled batches, suggesting that milling had altered the surface properties.