Stabilized topical formulations containing core-shell microcapsules

Patent metadata

Field	Value
Publication number	US-12053546-B2
Application number	US-201213537646-A
Country	US
Kind code	B2
Filing date	Jun 29, 2012
Priority date	Jun 29, 2011
Publication date	Aug 6, 2024
Grant date	Aug 6, 2024

Abstract

The present disclosure relates to compositions for topical application, where the compositions comprise microcapsules having a core that comprises benzoyl peroxide and a shell that comprises an inorganic polymer, microcapsules having a core that comprises a retinoid and a shell that comprises an inorganic polymer, and a stabilizing agent. The composition can be in a variety of forms, such as emulsion and gel.

First claim

What is claimed is:

1. A topical pharmaceutical composition, comprising:
a plurality of first core-shell microcapsules comprising a first core that comprises benzoyl peroxide and a first shell that comprises a first inorganic polymer, wherein said benzoyl peroxide is in an amount of from about 1% to about 6% by weight based on total weight of the composition, and benzoyl peroxide is the only active agent in said first core; and
a plurality of second core-shell microcapsules comprising a second core that comprises an oil phase comprising all-trans retinoic acid (ATRA) dispersed in said oil phase and at least one phase changing material, wherein said phase changing material is confined to said second core; and a second shell that comprises a second inorganic polymer, wherein said ATRA is in an amount of from about 0.05% to about 0.5% by weight based on total weight of the composition; wherein ATRA is the only active agent in said second core;
wherein the concentration of said phase changing material is less than about 10% by weight based on total weight of the composition;
wherein said phase changing material prevents the leaching of said ATRA from said core into said composition at room temperature;
wherein said ATRA is stable during the three months storage at 25° C.; and
wherein said composition is an oil in water emulsion comprising a polyoxylstearate and a glycerylstearate wherein the ratio of said polyoxylstearate to said glycerylstearate is in the range of 2:3 to 3:2;
wherein said phase changing material is not liquid at room temperature; and
wherein said second core has a viscosity of from about 5000 cP to about 1,000,000 cP.

2. The composition in accordance with claim 1 , further comprising:
an amount of an anti-microbial agent that is effective to: maintain the microbial count of the composition at a level that meets the criteria of USP 51, as measured by Antimicrobial Effectiveness Testing (AET) after storage of the composition at a storage condition of 40° C. for one month.

3. The composition in accordance with claim 2 , wherein:
said first shell comprises a first silica polymer;
said second core comprises an oil phase comprising all-trans retinoic acid (ATRA) dispersed in said oil phase and at least one phase changing material; and
said second shell comprises a second silica polymer.

4. The composition in accordance with claim 2 , wherein:
in said first core-shell microcapsules, said first shell comprises a first silica polymer, and the benzoyl peroxide is present in the composition in an initial amount of about 6% by weight, based on the total weight of the composition;
in said second core-shell microcapsules, said second core comprises an oil phase comprising all-trans retinoic acid (ATRA) dispersed in said oil phase and at least one phase changing material, and said second shell comprises a second silica polymer, the ATRA being present in the composition in an initial amount of about 0.1% by weight, based on the total weight of the composition; and
said antimicrobial agent is selected from the group consisting of methylparaben and imidazolidinyl urea.

5. The composition in accordance with claim 2 , wherein:
in said first core-shell microcapsules, said first shell comprises a first silica polymer, the benzoyl peroxide being present in the composition in an initial amount of about 3% by weight, based on the total weight of the composition;
in said second core-shell microcapsules, said second core comprises an oil phase comprising all-trans retinoic acid (ATRA) dispersed in said oil phase and at least one phase changing material, and said second shell comprises a second silica polymer, the ATRA being present in the composition in an initial amount of about 0.05% by weight, based on the total weight of the composition.

6. The composition in accordance with claim 1 , wherein at least one phase changing material is selected from the group consisting of a natural paraffin, a synthetic paraffin, an aliphatic alcohol, a fatty acid, C 10 -C 100 alkanes, C 10 -C 100 alkenes, C 10 -C 100 alkynes, carnauba wax, beeswax, and a mixture thereof.

7. The composition in accordance with claim 1 , wherein said polyoxylstearate is selected from the group consisting of Polyoxyl-8 stearate, Polyoxyl-20 stearate, Polyoxyl-40 stearate, and Polyoxyl-100 stearate.

8. The composition in accordance with claim 1 , wherein said glycerylstearate is selected from the group consisting of glyceryl mono-stearate, glyceryl di-stearate and mixtures thereof.

9. The composition in accordance with claim 1 , wherein the amount of said polyoxylstearate in said composition is in the range of 0.1% w/w to 30% w/w.

10. The composition in accordance with claim 1 , wherein the amount of said glycerylstearate in said composition is in the range of 0.1% w/w to 30% w/w.

11. The composition in accordance with claim 1 , wherein said composition further comprises at least one fatty alcohol.

12. The composition in accordance with claim 11 , wherein said at least one fatty alcohol is selected from the group consisting of octyl alcohol, 2-ethyl hexanol, nonyl alcohol, decyl alcohol, undecanol, dodecyl alcohol, tridecyl alcohol, tetradecyl alcohol, pentadecyl alcohol, cetyl alcohol, palmitoleyl alcohol, heptadecyl alcohol, cetostearyl alcohol, stearyl alcohol, isostearyl alcohol, elaidyl alcohol, oleyl alcohol, linoleyl alcohol, elaidolinolenyl alcohol, ricinoleyl alcohol, nonadecyl alcohol, arachidyl alcohol, heneicosyl alcohol, behenyl alcohol, erucyl alcohol, lignoceryl alcohol, ceryl alcohol, montanyl alcohol, cluytyl alcohol, myricyl alcohol, melissyl alcohol, geddyl alcohol, cetearyl alcohol and mixtures thereof.

13. The composition in accordance with claim 12 , wherein the amount of said at least one fatty alcohol in said composition is in the range of 0.2% w/w to 50% w/w.

14. The composition in accordance with claim 1 , wherein said composition further comprises a polyacrylic acid homopolymer or copolymer.

15. The composition in accordance with claim 1 , wherein said oil in said oil in water emulsion is selected from the group consisting of paraffin oil, isopropyl myristate, caprylic/capric triglyceride, squalane, squalene, almond oil, castor oil, olive oil, jojoba oil, sunflower oil, soybean oil, grape seed oil, dimethicone, cyclomethicone and mixtures thereof.

16. The composition in accordance with claim 15 , wherein said oil is present in the composition in an amount in the range of 0.05% w/w to 50% w/w.

17. The composition in accordance with claim 1 , wherein said water in said oil in water emulsion further comprises at least one water soluble humectant.

18. The composition in accordance with claim 17 , wherein said at least one water soluble humectant is selected from the group consisting of propylene glycol, glycerin, and polyethylene glycol-X, where X is in the range of 200 to 10,000.

Assignees

• Toledano Ofer
• Bar Simantov Haim
• Sertchook Hanan
• Sol Gel Tech Ltd

Inventors

• Toledano Ofer
• Bar-Simantov Haim
• Sertchook Hanan

Classifications

• A61K9/5084

  Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs (tablets containing such a mixture A61K9/2077) · CPC title

• A61K31/327

  Peroxy compounds, e.g. hydroperoxides, peroxides, peroxyacids · CPC title

• A61K31/203

  Retinoic acids {; Salts thereof} · CPC title

• A61K9/0014 Primary

  Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00) · CPC title

• A61K47/14

  Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters · CPC title