Intravaginal matrix drug delivery devices
View Patent ↗The present invention relates to a process for the preparation of an intravaginal matrix drug delivery device. The process comprises the steps of combining at least one therapeutic agent in a therapeutically effective amount with at least one biocompatible elastomeric polymer to form a mix; curing said mix in a mold having a shape of said intravaginal drug delivery device, to form a polymer matrix; and maturing said polymer matrix to form the intravaginal drug delivery device. The maturing step alters the release rate characteristics of a device prepared in accordance with the process of the invention.
1. A process for increasing the magnitude of the amount of at least one therapeutic agent released from an intravaginal matrix drug delivery device within the first 24 hours of use of an exponential (first order) release decay, the process consisting essentially of preparing an intravaginal matrix drug delivery device by the steps of:
combining 5% to less than 30% (w/w) of at least one therapeutic agent with at least one biocompatible silicone elastomeric polymer, to form a mix suitable for forming a shape-retaining polymer matrix, in which the at least one therapeutic agent has a solubility in silicone oil at 25° C. of less than 0.1 mg/ml;
curing said mix at 50-100° C. for 1-10 minutes or at 15-25° C. for 1-24 hours to form the shape-retaining polymer matrix; and
maturing said shape-retaining polymer matrix under temperature and time conditions sufficient to form the intravaginal drug delivery device to produce a device having altered release rate characteristics, in which said maturing step is carried out at 40-100° C. for 2-72 hours; wherein the magnitude of the amount of said at least one therapeutic agent released from said intravaginal matrix drug delivery device within the first 24 hours of use of an exponential (first order) release decay is increased compared to said shape-retaining polymer matrix that did not undergo the step of maturing.
2. A process according to claim 1 , in which said maturing step is carried out at 50-80° C. for 16-24 hours.
3. A process according to claim 1 , in which the maturing step is carried out under temperature and time conditions sufficient to produce a device whose release characteristics are substantially independent of shelf life.
4. A process according to claim 1 , in which the process additionally comprises a step of aging the matured polymer matrix.
5. A process according to claim 4 , in which the aging step is carried out at 15-30° C. for 5-40 days.
6. A process according to claim 4 , in which the maturing step and the aging step are carried out under temperature and time conditions sufficient to produce a device whose release characteristics are substantially independent of shelf life.
7. A process according to claim 1 , in which the at least one therapeutic agent is in a range of about 10 to about 20% (w/w).
8. A process according to claim 1 , wherein the increase in the magnitude of the amount of said at least one therapeutic agent released in the first 24 hours of use of the intravaginal drug delivery device is between 110.6% to 222.5%.
9. A process according to claim 2 , wherein the increase in the magnitude of the amount of said at least one therapeutic agent released in the first 24 hours of use of the intravaginal drug delivery device is between 110.6% to 222.5%.