Intranasal formulation

Patent metadata

Field	Value
Publication number	US-12324811-B2
Application number	US-201917415966-A
Country	US
Kind code	B2
Filing date	Dec 18, 2019
Priority date	Dec 18, 2018
Publication date	Jun 10, 2025
Grant date	Jun 10, 2025

Abstract

The present invention relates to the formulation of midazolam. In particular, the invention provides new midazolam formulation for intranasal administration. These formulations contain midazolam in a high concentration from about 1% to about 10% w/w of the formulation and process of preparation thereof.

First claim

We claim:

1. A pharmaceutical formulation in the form of an aqueous solution for intranasal administration comprising midazolam at a concentration of 5% w/w of the formulation, polysorbate 80 as a surfactant at a concentration of 2.5% w/w of the formulation and pharmaceutically acceptable excipients.

2. The formulation as claimed in claim 1 , wherein midazolam is used in the form of a free base.

3. The formulation of claim 1 , wherein the formulation comprises a pH adjusting agent selected from hydrochloric acid, hydrobromic acid, sulfuric acid, sulfonic acid, sulfenic acid, phosphoric acid, acetic acid, ascorbic acid, carbonic acid, citric acid, butyric acid, fumaric acid, glutaric acid, glycolic acid, α-ketoglutaric acid, lactic acid, malic acid, mevalonic acid, maleic acid, malonic acid, oxalic acid, pimelic acid, propionic acid, succinic acid, tartaric acid, or tartronic acid, sodium hydroxide (NaOH), acetate, citrate, prolamine, sodium lactate, carbonate and phosphate buffers and combinations thereof.

4. The formulation of claim 3 , wherein the pH adjusting agent is hydrochloric acid, lactic acid or combination thereof.

5. The formulation of claim 1 , wherein a pH adjusting agent is present in an amount of from 7.5% to 12.5% w/w of formulation.

6. The formulation of claim 1 , wherein the formulation comprises of chelating agent selected from sodium EDTA or disodium edetate or combinations thereof in amount of from 0.005% to 0.10% w/w of the total formulation.

7. The formulation of claim 6 , wherein the chelating agent is disodium edetate at an amount of 0.1% w/w of total formulation.

8. The formulation of claim 1 , wherein the formulation comprises of antimicrobial preservative selected from p-hydroxybenzoic acid ester, benzalkonium chloride, benzododecinium bromide, and the combination thereof in an amount of from 0.001% to 0.3% by w/w of the formulation.

9. The formulation of claim 8 , wherein the preservative is benzalkonium chloride at an amount of 0.02% w/w of formulation.

10. The formulation of claim 1 , wherein the formulation comprises a solvent system selected from water, methoxy-polyethylene glycol, polyethylene glycol, propylene glycol, ethanol and the combination thereof.

11. The formulation of claim 10 , wherein the solvent system does not contain ethanol.

12. The formulation of claim 1 , wherein the aqueous solution has a pH of less than 4.

13. The formulation of claim 1 , wherein a therapeutically effective dose of midazolam is achieved when the volume of formulation administered to each nostril is 50-150 uL per nostril.

Assignees

• Cipla Ltd

Inventors

• Malhotra Geena
• Singh Sarabjit
• Gandhi Kalindi
• Mittal Vipul

Classifications

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K47/186

  Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide · CPC title

• A61K47/183

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title

• A61K9/0043 Primary

  Nose · CPC title

• A61K47/14

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