The involuntary loss of urine while awake or asleep is a malodorous social stigma, commonly concealed by its embarrassed victim with a mountain of absorbent pads. An estimated l 0 million Americans are incontinent, at a cost of $10 billion/year. As much as 25 percent of nursing time in geriatric hospitals is consumed dealing with incontinence. The most common conditions are urge incontinence, stress incontinence, and neurogenic bladder disorders. Oxybutynin is commonly used for the treatment of urge incontinence and neurogenic bladder disorder, but not for stress incontinence. Conventional oxybutynin therapy involves a dose of 5 mg taken 3 times daily in the form of tablets. However, since its oral bioavailability is only 6-9 percent, an injection capable of delivering 1-2 mg/day for 30 days would cover the therapeutic range. The goal of this program is to develop a biodegradable injectable microsphere system for sustained release of oxybutynin. The microspheres will be targeted to deliver the drug for a period of one month. In preliminary studies, BIOTEK prepared several depot injectable formulations of oxybutynin microspheres using FDA approved biodegradable polylactide-co-glycolide polymer. The 6-month Phase I SBIR work will confirm the reproducibility and optimize the method of preparation of a depot formulation. It will characterize the properties of the microspheres and determine the rate of release of the drug m vitro and in rabbits. If successful, Phase II will focus on clinical evaluation of the formulation in volunteers at the West Roxbury VA Hospital in Massachusetts.
An injectable depot form of oxybutynin would find use in several conditions where chronic administration of the drug is known to be effective. The number of U.S. subjects who suffer from these conditions is high and the associated health cost is more than $10 billion/year. While oxybutynin is not the only mode of therapy, the choice is influenced by the low oral bioavailability and hence, the low dose of the drug. From a commercial standpoint, even a small penetration of this market would by itself represent an impressive business opportunity and ample return on investment.
