PHARMACEUTICAL SEMI-SOLID COMPOSITION OF ISOTRETINOIN

• US 20140107203A1
• Filed: 12/18/2013
• Published: 04/17/2014
• Est. Priority Date: 06/18/2012
• Status: Active Grant

• Current Assignee: Galephar Pharmaceutical Research Incorporated
• Original Assignee: Galephar Pharmaceutical Research Incorporated
• Inventors: DEBOECK, Arthur M., VANDERBIST, Francis, SERVAIS, Cecile, BAUDIER, Philippe
• Granted Patent: US 9,078,925 B2
• Time in Patent Office: Days
• US Class Current: 514/559
• CPC Class Codes: A61K 31/203 Retinoic acids ; Salts thereof
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0014 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 Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61K 9/4875 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/4858

Abstract

The invention relates to an oral pharmaceutical composition of isotretinoin at least two excipients, one of the excipients being a hydrophilic excipient having an HLB value greater than or equal to 10 and the other excipient being an oily vehicle. The oral pharmaceutical composition is substantially devoid of food effect as characterized by a dissolution profile wherein at least 70% of the oral pharmaceutical composition is dissolved after about four hours in a USP2 dissolution apparatus at a paddle speed of 100 rpm, and a dissolution media composed of 900 mL of pH 7.5 buffer containing 0.11% pancreatin, 4.7% cholic acid, 0.14% sodium dihydroxide phosphate and 0.5% sodium hydroxide at 37° C.

Claims

1. The oral pharmaceutical composition is substantially devoid of food effect as identified by a dissolution profile wherein at least 70% of the oral pharmaceutical composition is dissolved after about four hours in a USP 2 dissolution apparatus at a paddle speed of 100 rpm, and a dissolution media composed of 900 mL of pH 7.5 buffer containing 0.11% pancreatin, 4.7% cholic acid, 0.14% sodium dihydroxide phosphate and 0.5% sodium hydroxide at 37°

C.

2. The oral pharmaceutical composition of claim 1, wherein the oral pharmaceutical composition comprises at least two excipients, one of the excipients being a hydrophilic excipient having an HLB value greater than or equal to 10 and the other excipient being an oily vehicle.

3. The oral pharmaceutical composition of claim 2, wherein the hydrophilic excipient comprises one or more of glyceroyl macrogolglycerides 4. The oral pharmaceutical composition of claim 2, wherein the hydrophilic excipient comprises from about 20% to about 80% by weight of the pharmaceutical composition.

5. The oral pharmaceutical composition of claim 2, wherein the oily vehicle comprises one or more of vegetable oils, medium chain triglycerides, fatty acid esters, amphiphilic oil, glycerol oleate derivative, and mixtures thereof.

6. The oral pharmaceutical composition of claim 5, wherein the oil vehicle comprises from about 5% to about 70% by weight of the pharmaceutical composition.

7. The oral pharmaceutical composition of claim 2, wherein the hydrophilic excipient has an HLB value of greater than 12.

8. The oral pharmaceutical composition of claim 1, which further comprises from 1 to 10% by weight of at least one surfactant.

9. The oral pharmaceutical composition of claim 1, which further comprises at least one disintegrant.

14. The oral pharmaceutical composition of claim 1, wherein 6 capsules containing said composition are 92% dissolved in view of the parameters set forth in Table XIII of the present specification.

10. A method for dissolution of an isotretinoin-containing formulation that distinguishes between isotretinoin-containing formulations with and without a significant food effect, which comprises the steps of:

a) adding isotretinoin to melted excipients to form a mixture, and introducing the mixture into capsules,

b) dissolving the capsules,

c) determining whether the isotretinoin-containing formulation has a significant

food effect by assessing the dissolution of step b) in view of the parameters set forth in Table XIII of the present specification.

11. The method of claim 10, wherein no significant food effect is demonstrated if the result obtained for at least 6 capsules is at least 90% dissolved.

12. The method of claim 10, wherein the dissolving step b) is effected in accordance with Example 3 of the present specification.

13. The method of claim 10, which is used as a biorelevant dissolution test to assess bioequivalence of post-approval formulation changes in drug product form.