Natural combination hormone replacement formulations and therapies

A pharmaceutical composition comprising:

• a fill material encapsulated in a capsule, the fill material comprising:
• a. two active pharmaceutical ingredients, the active pharmaceutical ingredients being about 1 mg of 17β-estradiol and about 100 mg of progesterone, wherein a first portion of the progesterone is solubilized and a second portion of the progesterone is micronized, and the 17β-estradiol is fully solubilized;
• b. a solubilizing agent for the active pharmaceutical ingredients, the solubilizing agent comprising:
• i. a medium chain oil comprises mono- and diglycerides of capric and caprylic acid;
• and
• ii. at least one of lauroyl macrogol-32 glycerides or lauroyl polyoxyl-32 glycerides that is about 1% to about 2% by weight of the fill material;
• wherein the 17β-estradiol and the progesterone in the capsule are present in the solubilizing agent wherein the second portion of the progesterone is uniformly dispersed in the solubilizing agent;
• wherein the progesterone has a solubility in the solubilizing agent of at least about 73 mg/g, and the 17β-estradiol has a solubility in the solubilizing agent of at least about 10 mg/g;
• and wherein the progesterone is about 30% to about 35% by weight of the fill material, and the 17β-estradiol is about 0.1% to about 0.4% by weight of the fill material.

A pharmaceutical composition comprising:

• a fill material encapsulated in a capsule, the fill material comprising:
• a. two active pharmaceutical ingredients, the active pharmaceutical ingredients being about 1 mg of 17β-estradiol and about 100 mg of progesterone, wherein a first portion of the progesterone is solubilized and a second portion of the progesterone is micronized, and the 17β-estradiol is fully solubilized;
• b. a solubilizing agent for the active pharmaceutical ingredients, the solubilizing agent comprising:
• i. about 196 mg of mono- and diglycerides of caprylic and capric acid;
• and
• ii. about 3 mg of at least one of lauroyl macrogol-32 glycerides or lauroyl polyoxyl-32 glycerides;
• wherein the 17β-estradiol and the progesterone in the capsule are present in the solubilizing agent wherein the second portion of the progesterone is uniformly dispersed in the solubilizing agent;
• wherein the progesterone has a solubility in the solubilizing agent of at least about 73 mg/g, and the 17β-estradiol has a solubility in the solubilizing agent of at least about 10 mg/g;
• and wherein the progesterone is about 30% to about 35% by weight of the fill material and the 17β-estradiol is about 0.1% to about 0.4% by weight of the fill material.