Topical compositions and methods of using the same
The present invention generally relates to topical compositions and methods of using the same. A preferred topical pharmaceutical composition comprises a nitric oxide-releasing active pharmaceutical ingredient in admixture with a hydrophilic composition and a hydrophobic composition wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a nitric oxide-releasing compound having a diazeniumdiolate functional group.
1. A topical pharmaceutical composition comprising a hydrophobic composition in admixture with a hydrophilic composition,
wherein the hydrophobic composition comprises a nitric oxide-releasing co-condensed silica particle having a diazeniumdiolate functional group, a hydrophobic base, and an amphiphilic compound;
wherein the hydrophilic composition is an aqueous hydrogel having a pH in a range of about 4 to about 5 and the hydrogel comprises a buffer; and
wherein a ratio of the hydrophilic composition to the hydrophobic composition in the topical pharmaceutical composition is 4:1 or less.
2. The topical pharmaceutical composition of claim 1 , wherein the hydrophilic composition comprises a phosphate buffer.
3. The topical pharmaceutical composition of claim 1 , wherein the hydrophilic composition further comprises cellulose or a pharmaceutically acceptable salt thereof, chitosan, an acrylic acid polymer, or any combination thereof.
4. The topical pharmaceutical composition of claim 1 , wherein the hydrophilic composition further comprises a polyhydric alcohol.
5. The topical pharmaceutical composition of claim 1 , wherein the topical pharmaceutical composition is self-emulsifying.
6. The topical pharmaceutical composition of claim 1 , wherein the hydrophilic composition has a viscosity of about 5000 cP to about 100,000 cP.
7. The topical pharmaceutical composition of claim 1 , wherein the hydrophobic composition comprises:
nitric oxide-releasing co-condensed silica particles at a concentration from 0.1% to 30% by weight of the hydrophobic composition;
the hydrophobic base at a concentration from 65% to 95% by weight of the hydrophobic composition; and
the amphiphilic compound at a concentration from 2% to 10% by weight of the hydrophobic composition.
8. The topical pharmaceutical composition of claim 1 , wherein the topical pharmaceutical composition has a pH of about 3 to about 9.
9. The topical composition of claim 1 , wherein the hydrophobic base comprises mineral oil.
10. A kit comprising:
a hydrophilic composition, wherein the hydrophilic composition is an aqueous hydrogel having a pH in a range of about 4 to about 5 and the hydrogel comprises a buffer; and
a hydrophobic composition comprising an active pharmaceutical ingredient, a hydrophobic base; and an amphiphilic compound, wherein the active pharmaceutical ingredient comprises a nitric oxide-releasing co-condensed silica particle having a diazeniumdiolate functional group,
wherein a ratio of the hydrophilic composition to the hydrophobic composition in the kit is 4:1 or less.
11. The kit of claim 10 , wherein the hydrophilic composition further comprises:
a cellulose or a pharmaceutically acceptable salt thereof;
a polyhydric alcohol; and
water.
12. The kit of claim 10 , wherein the hydrophobic base comprises mineral oil.
13. The kit of claim 10 , wherein the hydrophilic composition and the hydrophobic composition are separately stored.
14. A method of stably storing a diazeniumdiolate modified macromolecule in a hydrophobic composition and releasing nitric oxide from the diazeniumdiolate modified macromolecule, the method comprising:
admixing the hydrophobic composition with a hydrophilic composition to form an admixture,
wherein the hydrophobic composition comprises a nitric oxide-releasing co-condensed silica particle having a diazeniumdiolate functional group, a hydrophobic base, and an amphiphilic compound,
wherein the hydrophilic composition is an aqueous hydrogel having a pH in a range of about 4 to about 5 and the hydrogel comprises a buffer, and
wherein a ratio of the hydrophilic composition to the hydrophobic composition in the admixture is 4:1 or less.
15. The topical pharmaceutical composition of claim 1 , wherein the buffer comprises acetic acid and an acetate.
16. The topical pharmaceutical composition of claim 1 , wherein the admixture has a pH in a range of about 4 to about 6.5.
17. The topical pharmaceutical composition of claim 1 , wherein the admixture has a pH in a range of about 4.5 to about 5.5.
18. The topical pharmaceutical composition of claim 1 , wherein the hydrogel maintains the pH of the admixture in a range of about 4 to about 6.5 for about 24 hours after combination.
19. The topical pharmaceutical composition of claim 1 , wherein the topical pharmaceutical composition has a single phase.
20. The topical pharmaceutical composition of claim 1 , wherein the amphiphilic compound comprises polyethylene glycol (PEG) caprylic/capric glyceride.
21. The topical pharmaceutical composition of claim 1 , wherein the nitric oxide-releasing compound in the hydrophobic composition is dispersed in an oil phase.
22. The topical pharmaceutical composition of claim 1 , wherein the hydrophilic composition comprises a phosphate buffer, and wherein the topical pharmaceutical composition is continuous.
23. The kit of claim 10 , wherein the hydrophobic composition comprises:
nitric oxide-releasing co-condensed silica particles at a concentration from 0.1% to 30% by weight of the hydrophobic composition;
the hydrophobic base at a concentration from 65% to 95% by weight of the hydrophobic composition; and
the amphiphilic compound at a concentration from 2% to 10% by weight of the hydrophobic composition.
24. The kit of claim 23 , wherein the hydrophobic base comprises mineral oil.