United States Patent:   5,965,160

Assignee:  Yissum Research Development Company of the Hebrew University of Jerusalem (Jerusalem, IL)

Filed:  January 9, 1998

A self-emulsifying oily formulation (SEOF) comprising an oil component and a surfactant, the SEOF being characterized in that the oil component comprises an oily carrier and a cationic lipid and optionally, a lipophilic oily fatty alcohol, the oil-in-water emulsion which forms upon mixture of the SEOF, having oily droplets which are positively charged.

GENERAL DESCRIPTION OF THE INVENTION

In accordance with the invention, a novel self-emulsifying oily formulation (SEOF) is provided. When the formulation of the invention is mixed with an aqueous solution, and the mixture is agitated, an oil-in-water emulsion is formed. According to a preferred embodiment of the invention the droplets in the so-formed emulsion have a diameter below about 0.2 .mu.m. Emulsions having tiny droplets as those obtainable in accordance with the invention, were hitherto obtainable only by employing a complex homogenization procedure involving the use of intricate equipment (see for example Benita et al, 1989, Drug Delivery Design, 4, 143-153).

An additional feature of the SEOF of the invention is that the droplets in the formed emulsion are positively charged, unlike the negatively charged emulsions achieved with prior art SEOF.

The SEOF of the invention comprises an oily carrier which may be a medium chain triglyceride (MCT) oil, a long chain triglyceride (LCT) oil, and an oily fatty acid derivative. In addition, the SEOF comprise also a cationic lipid. It has been found in accordance with the invention that the addition of a lipophilic alcohol is required for obtaining emulsion droplets in the submicron (<1 .mu.m) range. The inclusion of a lipophilic alcohol in the SEOF of the invention is thus preferred.

The present invention thus provides a self-emulsifying oily formulation (SEOF) comprising an oil component and a surfactant, the SEOF being characterized in that the oil component comprises an oily carrier and a cationic lipid and optionally, a lipophilic alcohol, the oil-in-water emulsion which forms upon mixture of the SEOF, having oily droplets which are positively charged.

The SEOF of the invention can be used as a delivery vehicle for hydrophobic drugs. When such a delivery vehicle, with the drugs dissolved therein, comes into contact with a body fluid, it spontaneously emulsifies forming tiny oily droplets with the drug contained therein.

One specific example of such a drug delivery vehicle is one which is intended for the oral systemic administration of hydrophobic drugs. For such administration, the SEOF with the dissolved drugs are preferably encapsulated.

The present invention thus provides a pharmaceutical preparation comprising an effective amount of a hydrophobic drug dissolved in a liquid carrier, the preparation being characterized in that said carrier is the above SEOF. Specific embodiments of said preparation is oral systemic preparations.

The term "effective amount" should be understood as meaning a dose of the drug effective in exerting a therapeutic effect. For an oral preparation of the invention, the term "effective amount" means a dose of the drug which after its absorption into the body through the walls of a GI tract, yield a drug concentration in the blood which is effective in exerting a therapeutic effect on a target organ.

The invention also provides a method for administration of a hydrophobic drug, to locations in the body, e.g GI tract, into the blood, etc . . . , where the preparation comes into contact with body fluids, comprising administering the drug in an oily vehicle being the above SEOF.

Another use of the SEOF of the invention is in a process for the production of emulsions, particularly such having droplets in the submicron range (submicron emulsions). A specific embodiment in the preparation of emulsions comprising a hydrophobic drug and intended to be used as pharmaceutical preparations. Thus, the present invention provides a process for the production of an emulsion, comprising mixing said SEOF with an aqueous solution and agitating the mixture. Where the emulsion is to be used as a carrier of hydrophobic drugs, the SEOF will have said drug dissolved therein.

Claim 1 of 22 Claims

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