Method for releasing an active principle contained a multiple emulsion

• US 6,627,603 B1
• Filed: 08/10/1999
• Issued: 09/30/2003
• Est. Priority Date: 08/07/1997
• Status: Expired due to Term

• Current Assignee: Centre National De La Recherche Scientifique
• Original Assignee: Centre National De La Recherche Scientifique
• Inventors: Bonnakdar, Lida, Ficheux, Marie-Françoise, Bibette, Jérôme, Leal Calderon, Fernando
• Primary Examiner(s): Dees, Jose′ G.
• Assistant Examiner(s): CHOI, FRANK I
• Application Number:
  US09/284,062
• Time in Patent Office: 1,512 Days
• Field of Search: 514/772, 514/873, 514/904, 514/937, 514/938, 514/942, 514/943, 514/969, 514/975, 514/3, 514/769, 514/784, 514/785, 514/885, 514/913, 514/941, 514/974, 424/400, 424/401, 424/94.1
• US Class Current: 514/5.9
• CPC Class Codes: A61K 9/113 Multiple emulsions, e.g. oil-in-water-in-oil A61K9/0026 takes precedence
• CPC Class Codes: B01D 17/047 with separation aids
• CPC Class Codes: B01F 23/4105 Methods of emulsifying
• CPC Class Codes: B01F 23/4141 High internal phase ratio [HIPR] emulsions, e.g. having high percentage of internal phase, e.g. higher than 60-90 % of water in oil [W/O]
• CPC Class Codes: B01F 23/4144 Multiple emulsions, in particular double emulsions, e.g. water in oil in water; Three-phase emulsions

Abstract

A method for the controlled release of an active principle contained in a multiple water-in-oil-in-water emulsion characterized in that the multiple emulsion comprises an invert emulsion Ei with an aqueous phase A1 containing at least a hydrophilic active principle. The emulsion Ei is dispersed in the form of direct emulsion droplets Ed, in a continuous aqueous phase A2, with the two emulsions Ed and Ei stabilized by at least a surfactant, present in their respective continuous phases. The multiple emulsion is brought in the presence of an effective amount of an agent for transforming it into a direct emulsion and induce the release of the active principle, contained in the aqueous phase A1 of emulsion Ei, in the aqueous phase A2.

Claims

1. A process for releasing an active principle comprising a multiple emulsion wherein the multiple emulsion comprises a water-in-oil-in water emulsion comprising an inverse emulsion Ei with an aqueous phase A1, in dispersion in the form of droplets of direct emulsion Ed, in a continuous aqueous phase A2, wherein the emulsion Ed is stabilized by a surfactant having an HLB of greater than 14 present in its continuous phase;

the emulsion Ei is stabilized by a surfactant having an HLB of less than 7 present in its continuous phase; and

the amount of the surfactant present in the aqueous phase A2 of the emulsion Ed is adjusted to an amount greater than the critical concentration threshold of this surfactant, for converting said multiple emulsion into a direct-emulsion, with a concentration threshold being between 7 and 20 CMC (Critical Micelle Concentration) for a surfactant having an HLB of the order of 40 and greater than 100 CMC for a surfactant having an HLB between 14 and 20 CMC;

wherein the active principle is in solution in the aqueous phase A1 and said active principle is released into the aqueous phase A2 by adjusting the concentration of the surfactant present in said aqueous phase A2 with the release time being shorter at concentrations equal to or greater than this surfactant'"'"'s critical concentration threshold.

2. The process according to claim 1, wherein an agent is added to the multiple emulsion, said agent is a surfactant identical to that present in the aqueous phase A2 of the emulsion Ed.

3. The process according to claim 1, wherein an agent is added to the multiple emulsion, said agent is a surfactant identical to that present in the aqueous phase A2 of the emulsion Ed and is introduced in an amount sufficient for its concentration in the aqueous phase A2 to be greater than its critical concentration threshold.

4. The process according to claim 1, wherein the surfactant present in the continuous aqueous phase A2 of the emulsion Ed is selected from the group consisting of lecithins which are soluble in water, sucrose esters, fatty acid esters, polyoxyethylenated alkylamides, triglyceride sulphates, alkyl sulphates, alkyl ether sulphates, alkyl sulphonates, alkylamine salts, fatty amines, lipoamino acids, alkyl betaines, alkyl polyglycol ethers, alkylene oxide copolymers, modified polyesters and polymeric silicone surface-active agents.

5. The process according to claim 1, wherein the surfactant present in the continuous phase of the emulsion Ei is selected from the group consisting of lecithins which are soluble in fats, esters of sorbitan and fatty acids, polyalkylene dipolyhydroxystearates, fatty acids, monoglycerides, polyglycerol esters, polyglycerol polyricinoleate and esters of lactic and tartaric acid.

6. The process according to claim 1, wherein the continuous phase of the emulsion Ei is an oily phase composed of at least one oil selected from the group consisting of mineral, vegetable and animal oils.

7. The process according to claim 1, wherein the active principle in solution in the aqueous phase A1 is a compound selected from the group consisting of vitamins, enzymes, insulin, analgesic, antimitotics, anti-inflammatories or antiglaucomas, vaccines, anti-cancer agents, narcotic antagonist, detoxification agents, depilatory agents, agents for correcting or masking taste, water-soluble salts, breaking agents, acids, bases, vinegar, glucose, colorants, preservatives or their mixtures.

8. The process according to claim 1, wherein the direct emulsion Ed comprises, by volume, from 50 to 99% of a continuous aqueous phase A2 per 1 to 50% of inverse emulsion Ei.

9. The process according to claim 1, wherein the inverse emulsion Ei is preferably composed, by volume, of 50 to 99% of a continuous phase per 1 to 50% of aqueous phase A₁.