Claims for Patent: 11,123,283

Summary for Patent: 11,123,283

Title:	Soluble estradiol capsule for vaginal insertion
Abstract:	According to various embodiments of this disclosure, pharmaceutical formulations comprising solubilized estradiol are provided. In various embodiments, such formulations are encapsulated in soft capsules which may be vaginally inserted for the treatment of vulvovaginal atrophy.
Inventor(s):	Bernick; Brian A. (Boca Raton, FL), Amadio; Julia M. (Boca Raton, FL), Persicaner; Peter H. R. (Boca Raton, FL), Thorsteinsson; Thorsteinn (Boynton Beach, FL), Cacace; Janice Louise (St. Petersburg, FL), Sancilio; Frederick D. (Stuart, FL), Irani; Neda (Palm Beach Gardens, FL)
Assignee:	TherapeuticsMD, Inc. (Boca Raton, FL)
Application Number:	16/837,937
Patent Claims:	1. A soft gelatin vaginal insert comprising a gelatin capsule encapsulating a fill comprising 1 to 10 mcg of estradiol in a solubilizing agent, the solubilizing agent comprising: a) a C8 to C10 triglyceride containing a fatty acid composition that comprises at least about 80% by weight caprylic (C8) acid and capric (C10) acid; and b) a nonionic surfactant comprising PEG-6 stearate, PEG-32 stearate, and ethylene glycol palmitostearate; wherein the fill does not contain a gelling agent and the solubilizing agent has a viscosity of between 50 and 380 cP as measured at 25.degree. C. 2. The soft gelatin vaginal insert of claim 1, wherein the gelatin capsule comprises 150 bloom, Type B gelatin, hydrolyzed collagen, and glycerin. 3. The soft gelatin vaginal insert of claim 2, wherein the gelatin capsule further comprises a sorbitan-sorbitol based soft gel plasticizer. 4. The soft gelatin vaginal insert of claim 1, wherein the fill has a mass of about 300 mg. 5. The soft gelatin vaginal insert of claim 1, wherein the gelatin capsule has an interior wall surface defining an inner space, wherein a maximal length defined by two points on opposing sides of the interior wall surface is about 0.69 inches. 6. The soft gelatin vaginal insert of claim 1, wherein the capsule has an interior wall surface defining an inner space and an exterior wall surface disposed over the interior wall surface defining a thickness, wherein the thickness measured perpendicular to the interior wall surface and the exterior wall surface is about 0.108 inches. 7. The soft gelatin vaginal insert of claim 1, wherein the solubilizing agent comprises a 9:1 ratio of C8 to C10 triglyceride containing a fatty acid composition to nonionic surfactant. 8. A soft gelatin vaginal insert comprising a gelatin capsule encapsulating a fill comprising 1 to 10 mcg of estradiol in a solubilizing agent, the solubilizing agent comprising a) a C8 to C10 triglyceride containing a fatty acid composition comprising at least about 80% by weight caprylic (C8) acid and capric (C10) acid, b) a nonionic surfactant comprising PEG-6 stearate, PEG-32 stearate, and ethylene glycol palmitostearate, wherein the fill does not contain a hydrodispersible agent and the solubilizing agent has a viscosity of between 50 and 380 cP as measured at 25.degree. C. 9. The soft gelatin vaginal insert of claim 8, wherein the gelatin capsule comprises 150 bloom, Type B gelatin, hydrolyzed collagen, and glycerin. 10. The soft gelatin vaginal insert of claim 8, wherein the gelatin capsule further comprises a sorbitan-sorbitol based soft gel plasticizer. 11. The soft gelatin vaginal insert of claim 8, wherein the fill has a mass of about 300 mg. 12. The soft gelatin vaginal insert of claim 8, wherein the gelatin capsule has an interior wall surface defining an inner space, wherein a maximal length defined by two points on opposing sides of the interior wall surface is about 0.69 inches. 13. The soft gelatin vaginal insert of claim 8, wherein the capsule has an interior wall surface defining an inner space and an exterior wall surface disposed over the interior wall surface defining a thickness, wherein the thickness measured perpendicular to the interior wall surface and the exterior wall surface is about 0.108 inches. 14. The soft gelatin vaginal insert of claim 8, wherein the solubilizing agent comprises a 9:1 ratio of C8 to C10 triglyceride containing a fatty acid composition to nonionic surfactant. 15. A soft gelatin vaginal insert consisting essentially of a soft gelatin capsule containing a fill material, the fill material consisting essentially of 1 to 10 mcg of estradiol and a solvent system, the solvent system consisting essentially of a 9:1 ratio of one or more C6 to C14 fatty acid mono-, di-, or triesters of glycerol to a nonionic surfactant, wherein the nonionic surfactant is not hydrophilic, and wherein the fill material has a viscosity of between 50 and 380 cP as measured at 25.degree. C. 16. The soft gelatin vaginal insert of claim 15, wherein the nonionic surfactant has an HLB value of less than about 10. 17. The soft gelatin vaginal insert of claim 15, wherein the nonionic surfactant has an HLB value of about 9 to about 10. 18. The soft gelatin vaginal insert of claim 15 wherein the insert is shaped with a wider bottom portion and a narrower top portion. 19. The soft gelatin vaginal insert of claim 15, wherein the vaginal insert is in the shape of a tear drop. 20. The soft gelatin vaginal insert of claim 15, wherein the vaginal insert is in the shape of a cone with a frustoconical end. 21. The soft gelatin vaginal insert of claim 15, wherein the vaginal insert is in the shape of a cylinder. 22. The soft gelatin vaginal insert of claim 21, wherein the vaginal insert is in the shape of a cylinder with a wider cap portion. 23. A soft gelatin vaginal insert comprising a gelatin capsule encapsulating a fill comprising 1 to 10 mcg of estradiol in a solubilizing agent, the solubilizing agent comprising a 9:1 ratio of: a) a C8 to C10 triglyceride containing a fatty acid composition comprising at least about 80% by weight caprylic (C8) acid and capric (C10) acid; to b) a nonionic surfactant comprising PEG-6 stearate, PEG-32 stearate, and ethylene glycol palmitostearate; wherein the solubilizing agent has a viscosity of between 50 and 380 cP as measured at 25.degree. C.; and wherein the soft gelatin vaginal insert does not raise systemic estradiol levels following administration. 24. The soft gelatin vaginal insert of claim 23, wherein the solubilizing agent comprises 270 mg of the C8 to C10 triglyceride and 30 mg of the nonionic surfactant.