A PHARMACEUTICAL OIL-IN-WATER NANO-EMULSION

• US 20170143627A1
• Filed: 06/25/2015
• Published: 05/25/2017
• Est. Priority Date: 06/25/2014
• Status: Active Grant

• Current Assignee: Synergia Life Sciences Pvt., Ltd.
• Original Assignee: Synergia Life Sciences Pvt., Ltd.
• Inventors: Misra, Ambikanandan
• Granted Patent: US 10,736,842 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• 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 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/26 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 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 9/0043 Nose
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• 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: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 : without antiinflammatory effect

Abstract

Accordingly, the present invention provides a pharmaceutical oil-in-water nano-emulsion, with a pharmaceutically active substance. The selected pharmaceutically active substance is encased in monounsaturated fatty acid droplets with the droplets having an average particle size in the range of 60 to 200 nm. The nano-emulsion is also provided with a non-ionic surfactant system, which is a mixture of polyethers, macrogolglycerides and polysaccharides, along with pharmaceutically acceptable adjuvants. The present invention also provides a process for the preparation of pharmaceutical oil-in-water nano-emulsion.

Claims

1. A pharmaceutical oil-in-water nano-emulsion, comprising:

a pharmaceutically active substance, encased in monounsaturated fatty acid droplets, said droplets having an average particle size in the range of 60 to 200 nm;

a non-ionic surfactant system comprising a mixture of polyethers, macrogolglycerides and polysaccharides; and

pharmaceutically acceptable adjuvants.

2. The composition as claimed in claim 1, wherein said pharmaceutically active substance is lipophilic or partially lipophilic and selected from a group consisting of antipsychotics, anti-emetics, analgesics, antipyretics, anti-inflammatory agents or any lipophilic based drugs.

3. The composition as claimed in claim 2, wherein said antipsychotics are ziprasidone, fluphenazine, haloperidol, olanzapine, chlorpromazine, risperidone, aripiprazole, molindone, loxapine, sulpiride, preferably olanzapine or risperidone and pharmaceutically acceptable salts thereof.

4. The composition as claimed in claim 2, wherein said anti-emetics are diphenhydrinate, diphenhydramine, doxylamine, meclizine, ondansetron, promethazine, prochlorperazine, preferably ondansetron or a pharmaceutically acceptable salts thereof.

5. The composition as claimed in claim 2, wherein said analgesics, antipyretics, anti-inflammatory agents are selected from methadone, diamorphine, fentanyl, buprenorphine, temazepam, piracetam, sufentanil, mefenamic acid, naproxen, piroxicam, indomethacin, valdecoxib, celecoxib, probenecid, nabumetone, ibuprofen, flurbiprofen, isoxicam, meclofenamic acid, fenclozic acid, phenyl butazone, preferably paracetamol.

6. The composition as claimed in claim 1, wherein said monounsaturated fatty acid is an oleic acid, in the range of about 5 to 25% w/w, preferably in the range of 7.5% to 10% w/w.

7. The composition as claimed in claim 1, wherein said polyether surfactant is a combination of polyethylene glycol in the range of 2 to 20% w/w and transcutol of 2.5 to 10% w/w.

8. The composition as claimed in claim 1, wherein said polyether surfactant is polyethylene glycol in the range of 2 to 20% w/w, preferably 15% w/w.

9. The composition as claimed in claim 1, wherein said macrogolglyceride surfactant is caprylocaproyl macrogol-8 glyceride or acconon CC 6, in the range of 12 to 25% w/w or a combination thereof.

10. The composition as claimed in claim 1, wherein said polysaccharide surfactant is selected from polyoxyethylene sorbitan fatty acid esters, preferably polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (80) sorbitan monooleate and sorbitan monooleate or a combination thereof.

11. The composition as claimed in claim 10, wherein said polysaccharide surfactant is in the range of 2 to 30% w/w, preferably from 5 to 25% w/w.

12. The composition as claimed in claim 1, wherein alternately benzyl alcohol, phenyl ethyl alcohol or chloro butanol is used as a co-solvent.

13. The composition as claimed in claim 1 wherein said adjuvants are stabilizers, antioxidants, preservatives, mucoadhesive agents, buffering agents, absorption enhancers and pH adjusting agents.

14. The composition according to claim 13, wherein said antioxidant, selected from butylated hydroxytoluene, butylated hydroxyanisole, ascorbic acid and tochopherol or a combination thereof in the range of 0.01% to 0.2% w/w.

15. The composition according to claim 13, wherein said absorption enhancers are selected from macrogol-15-hydroxystearate, sodium glychocolate and sodium caprylate or a combination thereof.

16. The composition as claimed in claim 1, wherein said composition adapted for nasal administration comprising:

a pharmaceutically active substance selected from olanzipine, ondansetron or respirodone;

in the presence of oleic acid, polyethylene glycol, caprylocaproyl macrogol-8 glyceride and polyoxyethylene (20) sorbitan monolaurate.

17. The composition as claimed in claim 16, wherein said composition is for use in the treatment or prevention of migraine, nausea, vomiting, psychosis, sleep disorders, respectively.

18. The composition as claimed in claim 1, wherein said composition adapted as an ocular solution comprising:

a pharmaceutically active substance paracetamol;

in the presence of polyethylene glycol;

caprylocaproyl macrogol-8 glyceride and polyoxyethylene (20) sorbitan monolaurate.

19. The composition as claimed in claim 18, wherein said ocular solution is for use in the treatment or reduction of intraocular pressure.

20. The use of composition as claimed in claim 16, in the manufacture of medicament for the treatment or prevention of nausea, vomiting, psychosis and sleep disorders.

21. The use of composition as claimed in claim 18, in the manufacture of medicament for the treatment or reduction of intraocular pressure.

22. A process for the preparation of an oil-in-water emulsion composition as claimed in claim 1, comprising the steps of

i) forming an oil phase in the presence of a monounsaturated fatty acid, a polyether surfactant, a macrogolglyceride surfactant and a polysaccharide surfactant, under stirring at an ambient temperature;

and

ii) adding a therapeutically amount pharmaceutically active substance to said oil phase, under constant stirring and at an ambient temperature, to encase said active substance, in said monounsaturated fatty acid droplets, said droplets with particle size in the range of 60 to 200 nm, to obtain a homogenous oil phase; and

iii) adding an aqueous medium to said homogenous oil phase, under stirring to obtain the oil-in-water emulsion.