PULSATILE RELEASE OF FSH FOR SUPEROVULATION IN CATTLE

The studies reported here were directed towards the development of an implantable microcapsule which ''pulses'' release of follicle stimulat ing hormone, FSH, for application to superovulating cows. Final dose f orms were administered using membrane-coated cylinders. The ''pulse'' of the FSH is achieved by membrane encapsulation of an effervescent/sw elling core containing citric acid, sodium bicarbonate, glucose and FS H. Entry of water results in sufficient pressure increase (by gas gene ration) to rupture (''burst'') the membrane. Time to rupture is depend ent upon several factors, such as membrane permeability and thickness, and core composition and loading. The final dose forms were Implanted by means of a trochar. This system was tested in sheep to substantiat e in vivo ''burst'' times and then tested in cows to determine efficac y. In vivo burst times in sheep varied from 8 to 96 hr, based upon max imal FSH values in blood serum, and generally paralled the planned tim es resulting from in vitro tests. Multiple capsules designed to releas e FSH as a pulse or steady state were tested on a limited number of co ws plus a control (n = IO). Four of the combinations resulted in II, 1 1, 14 and 16 ovulations, indicating that further development has promi se of providing a one-injection system using FSH for superovulating ca ttle.