Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Patent
1996-03-15
1998-05-12
Phelan, D. Gabrielle
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
424449, 514946, 514947, A61F 1302
Patent
active
057501378
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to the transdermal delivery of drugs and other biologically active agents. More particularly, this invention relates to novel methods and compositions for enhancing the percutaneous absorption of drugs when incorporated in transdermal drug delivery systems. More particularly, but without limitation thereto, this invention relates to the transdermal delivery of drugs utilizing a permeation-enhancing mixture of a monoglyceride and a lactate ester. Still more particularly, but without limitation thereto, this invention relates to the transdermal delivery of drugs utilizing a permeation-enhancing mixture of a monoglyceride and a lactate ester wherein the monoglyceride and lactate ester are present in the composition in specific weight percentages.
BACKGROUND OF THE INVENTION
The transdermal route of parenteral delivery of drugs provides many advantages over other administrative routes, and transdermal systems for delivering a wide variety of drugs or other beneficial agents are described in U.S. Pat. Nos. 3,598,122; 3,598,123; 3,731,683; 3,797,494; 4,031,894; 4,201,211; 4,286,592; 4,314,557; 4,379,454; 4,435,180; 4,559,222; 4,568,343; 4,573,995; 4,588,580; 4,645,502; 4,704,282; 4,788,062; 4,816,258; 4,849,226; 4,908,027; 4,943,435; and 5,004,610. The disclosures of the above patents are incorporated herein by reference.
In many instances, drugs which would appear to be ideal candidates or transdermal delivery are found to have such low permeability through intact skin that they cannot be delivered at therapeutically effective rates from reasonably sized systems.
In an effort to increase skin permeability, it has been proposed to pretreat the skin with various chemicals or to concurrently deliver the drug in the presence of a permeation enhancer. Various materials have been suggested for this purpose, as described in U.S. Pat. Nos. 3,472,931, 3,527,864, 3,896,238, 3,903,256, 3,952,099, 4,046,886, 4,130,643, 4,130,667, 4,299,826, 4,335,115, 4,343,798, 4,379,454, 4,405,616 and 4,746,515, all of which are incorporated herein by reference; British Pat. No. 1,001,949; and Idson, Percutaneous Absorption, J. Pharm. Sci., vol. 64, No. b6, Jun. 1975, pp 901-924 (particularly 919-921).
To be considered useful, a permeation enhancer should have the ability to enhance the permeability of the skin for at least one and preferably a significant number of drugs. More importantly, it should be able to enhance the skin permeability such that the drug delivery rate from a reasonably sized system (preferably 5-50 cm.sup.2) is at therapeutic levels. Additionally, the enhancer, when applied to the skin surface, should be non-toxic, non-irritating on prolonged exposure and under occlusion, and non-sensitizing on repeated exposure. Preferably, it should be capable of delivering drugs without producing topical reactions, burning or tingling sensations.
The present invention greatly increases drug permeability through the skin, and also reduces the lag time between application of the drug to the skin and attainment of the desired therapeutic effect.
While it is known in the art to combine permeation enhancers, see, e.g., European Patent Publication numbers 0295411 and 0368339, this invention utilizes a novel combination of a monoglyceride and a lactate ester. Further, the invention utilizes specific weight percentages of the novel components, the monoglyceride and lactate ester, i.e., 15 to 25 wt % of monoglyceride and 8 to 25 wt % of lactic acid ester. The combined effect and, further, specific weight percentages, produces a significant and surprising improvement i.e., more than an additive effect over use of either a monoglyceride or a lactate ester alone, as well as over the combination of monoglyceride and lactate ester in specified weight percentages.
SUMMARY OF THE INVENTION
The present invention relates to improved compositions and methods for improving the penetration of a broad category of beneficial agents that produce little or no skin irritation. The system of the inventio
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Tetrahedron Letters No. 20, pp. 1609-1612. Pergamon
Crisologo Nieves Marzan
Lee Eun Soo
Taskovich Lina Tormen
Yum Su Il
Phelan D. Gabrielle
Rafa Michael J.
Sabatine Paul L.
Stone Steven F.
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