Intranasal Formulation

Patent metadata

Field	Value
Publication number	US-2021379080-A1
Application number	US-201917415966-A
Country	US
Kind code	A1
Filing date	Dec 18, 2019
Priority date	Dec 18, 2018
Publication date	Dec 9, 2021
Grant date	—

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

1 . A pharmaceutical formulation for intranasal administration comprising midazolam at a concentration of from about 1% to about 10% w/w of the formulation, surfactant and pharmaceutically acceptable excipients.

2 . The formulation as claimed in claim 1 , wherein the concentration of midazolam is from about 3% to about 10% w/w of the formulation.

3 . The formulation as claimed in claim 1 , wherein the concentration of midazolam is from 5% w/w of the formulation.

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

5 . The formulation as claimed in claim 1 , wherein the formulation is an aqueous solution, microemulsion.

6 . The formulation as claimed claim 1 , wherein the surfactant is selected from sorbitan trioleate, lecithin, isopropylmyristate, tyloxapol, polyvinylpyrrolidone, polysorbate 80, vitamin E-TPGS, Myrj, Bijs, Span 20, Span 60, Arlacel 83, labrasol and macrogol-15-hydroxystearate or combinations thereof.

7 . The formulation as claimed in claim 1 wherein the surfactant is polysorbate 80.

8 . The formulation of claim 1 , wherein the surfactant is present in an amount of from about 0.5% to 2.5% w/w of total formulation.

9 . The formulation of claim 1 wherein the ratio of midazolam to surfactant is from about 1:0.01 to about 1:1.

10 . The formulation of claim 1 wherein the ratio of midazolam to surfactant is 1:0.5.

11 . (canceled)

12 . The formulation of claim 1 , wherein the formulation comprises pH regulators selected from hydrochloric, hydrobromic acid, sulfuric acid, sulfonic acid, sulfenic acid, phosphoric acid aliphatic carboxylic acids, such as acetic acid, ascorbic acid, carbonic acid, citric acid, butyric acid, fumaric acid, glutaric acid, glycolic acid, a-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), buffers such as acetate, citrate, prolamine, sodium lactate, carbonate and phosphate buffers and combinations thereof and combinations thereof.

13 . The formulation of claim 12 , wherein the pH regulator is hydrochloric acid-, lactic acid or combination thereof.

14 . The formulation of claim 1 , wherein the pH regulator is present in an amount of from about 7.5% to about 12.5% w/w of formulation.

15 . The formulation of present invention wherein the formulation comprises of chelating agent selected from editic acid or a salt thereof, such as sodium EDTA or disodium EDTA dehydrate and the like or combinations thereof in amount of from about 0.005% to 0.10% w/w of the total formulation.

16 . The formulation of claim 1 , wherein the chelating agent is disodium edetate at an amount of 0.1% w/w of total formulation.

17 . 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 about 0.001% to about 0.3% by w/w of the formulation.

18 . The formulation of claim 17 , wherein the preservative is benzalkonium at an amount of 0.02% w/w of formulation.

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

20 . The formulation of claim 1 , wherein the solvent system does not contain ethanol.

21 . (canceled)

22 . The formulation of claim 1 , wherein the pH of the composition is less than 4.

23 . (canceled)

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

25 . (canceled)

Assignees

• Cipla Ltd

Inventors

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

Classifications

• A61K47/186

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

• 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

• A61K47/14

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

• A61K31/5517 Primary

  condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam · CPC title

• A61K9/0043 Primary

  Nose · CPC title