Linker-Based Lecithin Microemulsion Delivery Vehicles

• US 20080139392A1
• Filed: 12/12/2006
• Published: 06/12/2008
• Est. Priority Date: 12/12/2006
• Status: Active Grant

• Current Assignee: Edgar Joel Acosta-Zara, Shuhong Yuan
• Original Assignee: Edgar Joel Acosta-Zara, Shuhong Yuan
• Inventors: Acosta-Zara, Edgar Joel, Yuan, Shuhong
• Granted Patent: US 9,918,934 B2
• Time in Patent Office: Days
• US Class Current: 504/359
• 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 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0043 Nose
• 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 23/02 Local anaesthetics
• CPC Class Codes: B01F 23/4143 Microemulsions
• CPC Class Codes: C09K 23/14 Derivatives of phosphoric acid

Abstract

The present invention relates to biocompatible microemulsion systems designed for controlled release drug delivery applications formulated with phospholipids such as lecithin (surfactant), a lipophilic additive (linker) containing 9 or more carbons in their alkyl group and hydrophilic-lipophilic balance (HLB) of 5 or less, and a surfactant-like hydrophilic additive (linker) containing between 6 to 9 carbon atoms in their alkyl tail. The combination of linkers and phospholipids produce formulations capable of delivering high concentrations of poorly soluble drugs into epithelial tissue using low surfactant concentrations, with minimum cytotoxic side effects.

Claims

1. A microemulsion as a vehicle for delivery of an active ingredient, the microemulsion comprising:

(a) a lecithin compound;

(b) a lipophilic additive; and

(c) a hydrophilic additive.

2. The microemulsion of claim 1 wherein the microemulsion is biocompatible and the delivery is topical, transdermal, oral, transnasal or intravenous.

3. The microemulsion of claim 1 wherein the microemulsion is water in oil (Type II) and topical or transdermal delivery produces an extended release profile.

4. The microemulsion of claim 1 wherein the lecithin compound is 0.1% to 8.0% w/w.

5. The microemulsion of claim 4 wherein the lecithin compound comprises at least 90% w/w of mono or di-alkyl phosphatidylcholines.

6. The microemulsion of claim 4 wherein the lecithin compound is obtained from animal, vegetable or chemical synthesis sources.

7. The microemulsion of claim 1 wherein the lipophilic additive is 0.1% to 24.0% w/w.

8. The microemulsion of claim 7 wherein the lipophilic additive consists of one or more ingredients selected from a group consisting of long chain alcohols, long chain fatty acids, monoglyceride, and sorbitan ester.

9. The microemulsion of claim 7 wherein the lipophilic additive consists of one or more ingredients selected from a group consisting of dodecyl alcohol, oleyl alcohol, cholesterol, lauric acid, palmitic acid, oleic acid, omega 6-fatty acids, omega 3-fatty acids, esters of these fatty acids with sorbitol, maltitol, xylitol, isomalt, lactitol, erythritol, pentaerythritol, glycerol;

for example, sorbitan monooleate, and glycerol monooleate.

10. The microemulsion of claim 1 wherein the hydrophilic additive is 0.1% to 24.0% w/w.

11. The microemulsion of claim 10 wherein the hydrophilic additive comprises C6-C9 fatty acids partially saponified.

12. The microemulsion of claim 10 wherein the hydrophilic additive consists of one or more ingredients selected from a group consisting of C6-C9 alkyl sulfates, sulfonates, phosphates, phosphonates, carboxylates, sulfosuccinates;

octanoates, octyl sulfonates, dibuthyl sulfosuccinates, C6-C9 carboxylic acids, alpha-hydroxy acids, esters of polyhydric alcohols, glucosides, secondary ethoxylated alcohols, pyrrolidones, octanoic acid, 2-hydroxyoctanoic acid, hexyl and octyl polyglucosides, octyl pyrrolidone, C6-C9 amines, quaternary ammonium salts, amine oxides, octylamine;

for example, C6-C9 alkyl aminopropionic acids, betaines, sulfobetaines, phosphatidylcholines, octyl sulfobetaine, and dibutyryl phosphatidylcholine.

13. The microemulsion of claim 10 wherein the hydrophilic additive is a mixture of octanoic acid and sodium octanoate.

14. The microemulsion of claim 1 further comprising a carrier oil.

15. The microemulsion of claim 14 wherein carrier oil is 0-95% w/w.

16. The microemulsion of claim 14 wherein the carrier oil is consists of alkyl esters of fatty acids, terpenes, or mixtures of monoglycerides, diglycerides or triglycerides.

17. The microemulsion of claim 1 wherein water is up to 90% w/w.

18. The microemulsion of claim 17 further comprising electrolytes to produce an isotonic formulation.

19. The microemulsion of claim 1 wherein the active ingredient is a drug having an aqueous solubility of less than 1% w/w in isotonic solutions at room temperature, and wherein the drug is soluble in a carrier oil.

20. The use of the microemulsion of claim 1 as a permeation enhancer and wetting agent for the delivery of agrochemicals through waxy cuticles of plant leaves.

21. A method for controlling the delivery of an active ingredient, the method comprising:

(a) forming a microemulsion by combining;

(i) a lecithin compound;

(ii) a lipophilic additive; and

(iii) a hydrophilic additive;

(b) dissolving the active ingredient into a carrier oil to form an active ingredient solution; and

(c) combining the microemulsion with the active ingredient solution.

22. The method of claim 21 wherein the delivery is topical, transdermal, oral, transnasal or intravenous.

23. The method of claim 21 wherein microemulsion is water in oil (Type II) and topical or transdermal delivery produces an extended release profile.

24. The method of claim 21 wherein the lipophilic additive is sorbitan monooleate, glycerol monooleate or oleic acid and wherein the hydrophilic additive is a mixture of octanoic acid and sodium octanoate.

25. The method of claim 21 wherein the carrier oil is alkyl esters of fatty acids, terpenes, or mixtures of monoglycerides, diglycerides or triglycerides.

26. The method of claim 21 wherein the microemulsion is an oil in water (Type I) and oral and intravenous delivery.

27. The method of claim 21 wherein the microemulsion is a bicontinuous microemulsion (Type III or IV) and topical transdermal, oral, transnasal or intravenous delivery.