Methods of manufacturing topical compositions and apparatus for the same

Patent metadata

Field	Value
Publication number	US-9757397-B2
Application number	US-201314133973-A
Country	US
Kind code	B2
Filing date	Dec 19, 2013
Priority date	Jul 5, 2011
Publication date	Sep 12, 2017
Grant date	Sep 12, 2017

Abstract

Provided according to some embodiments of the invention are methods of manufacturing a pharmaceutical composition. In some embodiments, such methods include homogenizing at a first excipient composition that includes a viscosity agent and at least one solvent to form a first premix composition; separately homogenizing at least one active pharmaceutical ingredient (API) and a second excipient composition to form a second premix composition; and combining the first premix composition and the second premix composition to form the composition. The pre-mixing of constituents may increase the stability of the API and provide uniformity of the dispersion of the constituents throughout the final topical composition.

First claim

That which we claim is:

1. A method of manufacturing a pharmaceutical composition comprising:
homogenizing a first excipient composition comprising at least one viscosity agent and at least one solvent selected from the group consisting of isopropyl alcohol, ethanol, and a combination thereof in an amount of about 50% to about 90% by weight of the pharmaceutical composition to form a first premix composition, wherein the first premix composition is a suspension:
separately mixing at least one active pharmaceutical ingredient (API) and a second excipient composition to form a second premix composition, wherein the at least one API comprises nitric oxide-releasing particles comprising diazeniumdiolate-functionalized co-condensed silica and the second premix composition is a suspension:
combining the first premix composition and the second premix composition; and homogenizing the combined first premix composition and second premix composition to form the pharmaceutical composition,
wherein a homogenizer is used to form the first premix composition and to homogenize the combined first premix composition and second premix composition, and
wherein the pharmaceutical composition is a suspension and the nitric oxide-releasing particles are dispersed in the suspension.

2. The method of claim 1 , wherein the composition is anhydrous.

3. The method of claim 2 , wherein the first excipient composition further comprises at least one humectant.

4. The method of claim 3 , wherein the second excipient composition comprises at least one humectant and/or at least one water repellant.

5. The method of claim 4 , wherein
the concentration of the viscosity agent in the pharmaceutical composition is in a range of 0.5 to 30 weight percent;
the concentration of the at least one API in the topical composition is in a range of 0.1 to 10 weight percent;
the concentration of the humectant in the topical composition is in a range of 2 to 20 weight percent; and
the concentration of the water repellant in the topical composition is in a range of 0.5 to 15 weight percent.

6. The method of claim 1 , wherein homogenizing the first excipient composition is performed at a rate in a range of 2,500 to 10,000 rpm.

7. The method of claim 1 , wherein
the first excipient composition is homogenized in a first vessel to form the first premix composition;
the at least one API and the second excipient composition are separately mixed in the first vessel to form the second premix composition; and
the first premix composition and the second premix composition are combined in a second vessel.

8. The method of claim 7 , wherein the first premix composition is transferred from the first vessel to the second vessel by a positive displacement pump at a transfer rate that avoids gelation.

9. The method of claim 7 , wherein homogenizing the first excipient composition comprises recirculating the first excipient composition through an in-line homogenizer.

10. The method of claim 1 , further comprising packaging the pharmaceutical composition.

11. The method of claim 1 , wherein homogenizing the first excipient composition comprises adding the at least one viscosity agent to the at least one solvent at a rate in a range of 0.5 to 50 g of the at least one viscosity agent per min per liter of the at least one solvent to form the first premix composition.

12. The method of claim 1 , wherein the pharmaceutical composition is in the form of a gel.

13. The method of claim 1 , wherein homogenizing the first excipient composition comprises homogenizing the first excipient composition at a first temperature in a range of 0° C. to 25° C., and homogenizing the combined first premix composition and second premix composition comprises homogenizing the combined first premix composition and second premix composition at a second temperature in a range of 0° C. to 25° C.

14. The method of claim 13 , wherein the first temperature is in a range of 0° C. to 22° C. and/or the second temperature is in a range of 0° C. to 22° C.

Assignees

• Novan Inc

Inventors

• Kougoulos Eleftherios
• Stasko Nathan

Classifications

• A61K47/38

  Cellulose; Derivatives thereof · CPC title

• B01F15/00071

  Operations & Transport · mapped topic

• A61K31/655 Primary

  Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds · CPC title

• B01F15/00012

  Operations & Transport · mapped topic

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title