Transdermal drug preparation

Details Transdermal drug preparation Transdermal drug preparation

1996-01-16

1998-04-14

Page, Thurman K.

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Liposomes

424405, 424 45, A61K 9127, A61K 906, A61K 910

Patent

active

057388695

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

1. Field of the Invention
This invention relates to a transdermal drug combination containing phospholipid, alcohol and vitamin E.
2. Prior Art
The transdermal administration of drugs, for example anti-inflammatory or antithrombotic drugs, is appropriate in cases in which a high local concentration of the drugs in the tissue under the intact skin is necessary, while oral or parenteral systemic administration leads to undesirable systemic side effects or it is not possible for this type of administration to offer the local concentration necessary. Drugs such as heparin sodium are in general employed topically in high concentrations because of low skin permeability. The intestinal absorption of this drug is negligible. Systemic effects are undesirable in the case of peripheral injuries. Many topical drug formulations may sensitize, dry out or even damage the skin where they are applied. Water-containing creams or ointments, which are often intended to avoid some of these undesirable side effects, must contain microbiological preservatives which for their part often lead to skin sensitization. There is therefore a need for safer, non-irritant absorption accelerators which additionally protect the skin and which, for drugs having a low skin permeation ability, are advantageous for increasing the drug concentration in the target tissue. Diclofenac sodium is an example of a non-steroidal anti-inflammatory drug (NSAID) which is employed extremely often, specifically in view of its problem-free and well-established clinical efficacy. In order to decrease the known local mucosal irritations after oral administration, topical administration forms are desirable for chronic use in the case of regional rheumatic symptoms. Metabolism in the first passage after oral administration, which occurs in the liver and leads to partial inactivation, can also be avoided by topical administration. In the following exposition, diclofenac was selected as an example of drugs having a low skin permeation ability.
The efficacy of topical diclofenac sodium preparations depends greatly on the capacity of the preparation to allow the drug to penetrate the intact skin. In particular, the horny layer represents a barrier for any drug permeation of the skin and penetration into the underlying inflamed tissue. Since the permeability of intact skin for diclofenac sodium is low, various experiments have been undertaken to increase skin permeation by use of various salts. IL-A-62 160 describes amine salts of diclofenac for increased skin penetration. DE-A-3 336 047 (=GB-A-2 128 087) describes a topical preparation based on an oil-in-water emulsion, which contains the diethylammonium salt of diclofenac. This salt is more lipophilic than the sodium salt and can permeate the skin at a higher rate. The use of this salt, however, is not without risk. It is known that secondary amines form highly carcinogenic nitrosamines. The preparation additionally contains diethylamine as a neutralizing agent for acrylic acid, which acts as a gel-forming agent for the gel preparation. Since secondary amines have these potential side effects, the German authorities responsible for registration (BGA) have recommended the replacement of these amines in cosmetic and pharmaceutical preparations. EP-A-0 372 527 describes the use of a hydroxyethylpyrrolidine salt of diclofenac having a higher water solubility than in the case of the sodium salt. This salt was combined with various absorption promoters, for example ethoxylated glycerides, lanolin esters or lecithin. Only in combination with these new salts were the absorption promoters able to accelerate the absorption to such an extent as the diethylamine salt. For this, compare Clin. Tri. J., 26 (1989) 304-309 (Galzigna et al.: percutaneous absorption of diclofenac after topical application, two different gel formulations). JP-A-02.049 722 describes the use of ammonia as a neutralizing agent for polyacrylic acid gels containing diclofenac sodium. If, as a neutralizing agent, not ammonia, but

REFERENCES:
patent: 4239754 (1980-12-01), Sache et al.
patent: 4711906 (1987-12-01), von Stetten
patent: 4745105 (1988-05-01), Griffin et al.
patent: 4745107 (1988-05-01), Foley et al.
patent: 5482965 (1996-01-01), Rajadhyaksha
patent: 5498420 (1996-03-01), Edgar et al.

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