Low dose oral pharmaceutical composition of isotretinoin

Patent metadata

Field	Value
Publication number	US-9750711-B2
Application number	US-201715444571-A
Country	US
Kind code	B2
Filing date	Feb 28, 2017
Priority date	Oct 1, 2014
Publication date	Sep 5, 2017
Grant date	Sep 5, 2017

Abstract

The present invention provides a low dose oral pharmaceutical composition of isotretinoin having reduced food effect, in particular no food effect. The present invention further relates to a process for preparing the oral pharmaceutical composition of the present invention.

First claim

The invention claimed is:

1. An oral pharmaceutical composition in the form of a capsule comprising isotretinoin and a pharmaceutically acceptable excipient, wherein the composition has a mean C max value in the range of about 9 ng/mL/mg to about 40 ng/mL/mg when administered in a dose of about 0.4 mg/kg to about 1.6 mg/kg of the body weight in a human subjects under fasting conditions.

2. The oral pharmaceutical composition in the form of a capsule of isotretinoin according to claim 1 wherein the composition has AUC 0-t in the range of about 125 ng·h/mL/mg to about 500 ng·h/mL/mg under fasting condition.

3. The oral pharmaceutical composition in the form of a capsule of isotretinoin according to claim 2 wherein composition exhibits mean fed/fasted ratio of AUC 0-t value of about 0.9 to about 1.40.

4. The oral pharmaceutical composition in the form of a capsule composition according to claim 1 wherein the composition is in the form of a dispersion which is further filled into the capsules.

5. The oral pharmaceutical composition in the form of a capsule composition according to claim 1 wherein the isotretinoin is micronized and has D 90 less than 30 μm.

6. The oral pharmaceutical composition in the form of a capsule composition according to claim 1 wherein the isotretinoin is present in an amount of about 5.5% to about 15% based on the total weight of the composition.

7. The oral pharmaceutical composition in the form of a capsule composition according to claim 1 wherein the composition further comprises a surfactant.

8. The oral pharmaceutical composition in the form of a capsule composition according to claim 7 wherein the surfactant is selected from the group consisting of anionic, cationic or non-ionic surfactants, sorbitan fatty acid esters; polysorbates; mononylphenyl ethers of polyethyleneglycols; dioctyl sodium sulfosuccinate, sodium lauryl sulphate, lecithin, fatty acid esters of propylene glycol, fatty acid esters of glycerol, poloxamers, and mixtures thereof.

9. The oral pharmaceutical composition in the form of a capsule according to claim 1 , wherein the composition releases not less than 50% of isotretinoin in 15 minutes when measured in United States Pharmacopeia (USP) type II dissolution apparatus, paddle at 75 rpm, in 900 mL of pH 7.4 phosphate buffer with 70 mg/L pancreatin and 4.5% LDAO as 30% solution with spiral coated sinker.

Assignees

• Sun Pharmaceutical Ind Ltd

Inventors

• Madan Harish Kumar
• Venkateshwaran Rathinasabapathy
• Madan Sumit
• Kochhar Ravi

Classifications

• A61K9/4858

  Organic compounds · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K31/203 Primary

  Retinoic acids {; Salts thereof} · CPC title

• A61K9/4875

  Compounds of unknown constitution, e.g. material from plants or animals (oils, fats, waxes, shellac A61K9/4858) · CPC title

• A61K9/148

  with compounds of unknown constitution, e.g. material from plants or animals (with oils, fats, waxes, shellac A61K9/145) · CPC title