Claims for Patent: 11,116,717

Summary for Patent: 11,116,717

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:	16/837,933
Patent Claims:	1. A soft gelatin vaginal insert containing a fill material having a viscosity between 50 and 380 cP as measured at 25.degree. C., the fill material comprising one or more C6 to C14 fatty acid mono-, di-, or triesters of glycerol, a nonionic surfactant comprising PEG-6 stearate and ethylene glycol palmitostearate, and 1 to 10 mcg of estradiol, wherein estradiol is the only active ingredient in the vaginal insert; further wherein the insert is made by a process comprising: a) making a pre-fill material consisting of: i. one or more C6 to C14 fatty acid mono-, di-, or triesters of glycerol; ii. a nonionic surfactant consisting of PEG-6 stearate, PEG-32 stearate, and ethylene glycol palmitostearate; and iii. 1 to 10 mcg of estradiol; b) forming a soft gelatin capsule, c) filling the soft gelatin capsule with the pre-fill material to make the insert. 2. The soft gelatin vaginal insert of claim 1, wherein the one or more C6 to C14 fatty acid mono-, di-, or triesters of glycerol is a C8 to C10 fatty acid triglyceride composition that is at least about 80% by weight caprylic (C8) acid and capric (C10) acids. 3. The soft gelatin vaginal insert of claim 1, wherein forming the pre-fill material comprises: a) optionally heating one or more C6 to C14 fatty acid mono-, di-, or triesters of glycerol; b) adding the nonionic surfactant to the one or more C6 to C14 fatty acid mono-, di-, or triesters of glycerol to form a mixture; and c) adding estradiol to the mixture. 4. The soft gelatin vaginal insert of claim 3, wherein heating is not optional. 5. The soft gelatin vaginal insert of claim 4, wherein heating comprises heating the one or more C6 to C14 fatty acid mono-, di-, or triesters of glycerol to a temperature ranging from about 35.degree. C. to about 45.degree. C. 6. The soft gelatin vaginal insert of claim 1, wherein the fill material contained within the soft gelatin capsule has a mass of about 300 mg. 7. The soft gelatin vaginal insert of claim 1, wherein the pre-fill material comprises a 9:1 ratio of one or more C6 to C14 fatty acid mono-, di-, or triesters of glycerol to nonionic surfactant. 8. The soft gelatin vaginal insert of claim 1, wherein the nonionic surfactant has an HLB value of less than about 10. 9. The soft gelatin vaginal insert of claim 1, wherein the nonionic surfactant has an HLB value of about 9 to about 10. 10. The soft gelatin vaginal insert of claim 1, wherein the insert is shaped with a wider bottom portion and a narrower top portion. 11. The soft gelatin vaginal insert of claim 1, wherein the vaginal insert is in the shape of a tear drop. 12. 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 consisting essentially of PEG-6 stearate, PEG-32 stearate, and ethylene glycol palmitostearate, wherein the fill material has a viscosity of between 50 and 380 cP as measured at 25.degree. C. 13. The soft gelatin vaginal insert of claim 12, wherein the soft gelatin capsule consists essentially of 150 bloom, Type B gelatin, hydrolyzed collagen, glycerin, and, optionally, a sorbitan-sorbitol based soft gel plasticizer. 14. The soft gelatin vaginal insert of claim 12, wherein the fill material has a mass of about 300 mg. 15. The soft gelatin vaginal insert of claim 12, wherein the 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. 16. The soft gelatin vaginal insert of claim 12, 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. 17. A soft gelatin vaginal insert comprising a soft gelatin capsule containing a fill material, the fill material comprising 1 to 10 mcg of estradiol and a solvent system, the solvent system consisting essentially of a 9:1 ratio of (i) one or more C6 to C14 fatty acid mono-, di-, or triesters of glycerol to (ii) an excipient composition that does not increase the irritancy of the solvent system, the fill material having a viscosity of between 50 and 380 as measured at 25.degree. C. 18. The soft gelatin vaginal insert of claim 17, wherein the excipient composition has an HLB value of less than about 10. 19. The soft gelatin vaginal insert of claim 17, wherein the excipient composition has an HLB value of about 9 to about 10. 20. The soft gelatin vaginal insert of claim 17, wherein the insert is shaped with a wider bottom portion and a narrower top portion. 21. The soft gelatin vaginal insert of claim 17, wherein the vaginal insert is in the shape of a tear drop, a cone with a frustoconical end, or a cylinder with a wider cap portion.