MICRO-NEEDLE ARRAY COMPRISING A COLOR CHANGE INDICATOR

Abstract

The invention relates to a microneedle array and to the use thereof for intradermal delivery, comprising a plurality of microneedles on a carrier, wherein this microneedle array is suitable for penetrating the skin of humans or animals and includes at least one color change indicator.

Claims

1. A microneedle array for use with intradermal delivery, comprising a plurality of microneedles on a carrier, characterized in that the microneedles comprise at least one color change indicator, the microneedles comprising at least one active ingredient and the microneedles comprising at least one polymer made of biodegradable polymers, biocompatible polymers or water-soluble polymers, a color change or color shift indicating a sufficient penetration depth into the stratum corneum, characterized in that the color change indicator is an integral part of the microneedles, the at least one color change indicator being introduced or incorporated into the microneedles.

2. The microneedle array for use according to claim 1, characterized in that the color change indicator is added during the production of the microneedles.

3. The microneedle array for use according to claim 1, characterized in that the microneedles comprise at least one active ingredient.

4. The microneedle array for use according to claim 1, characterized in that the color change indicator is at least one pH indicator.

5. The microneedle array for use according to claim 4, characterized in that the color change indicator is at least one physiologically acceptable pH indicator.

6. The microneedle array according to claim 1, characterized in that the color change indicator is a compound selected from chromoionophores or fluoroionophores, the compound being composed of at least one ionophore covalently bound to at least one molecule, which is selected from chromophores and fluorophores.

7. The microneedle array for use according to claim 6, characterized in that the chromophores or fluorophores are selected from the neutral, acidic or basic nitrated benzene dyes, neutral, acidic or basic azo dyes, quinone dyes.

8. The microneedle array according to claim 1, characterized in that the color change indicator is ink.

9. The microneedle array according to claim 1, characterized in that the color change indicator detects endogenous enzymes.

10. The microneedle array for use according to claim 1, characterized in that the color change indicator is included in the tip of the microneedles.

11. The microneedle array for use according to claim 1, are visible on the skin to the naked eye.

12. The microneedle array for use according to claim 1, characterized in that microneedles made of biodegradable polymers, biocompatible polymers or water-soluble polymers.

13. The microneedle array for use according to claim 1, characterized in that the microneedle array comprises fixation.

14. The microneedle array for use according to claim 1, wherein the microneedle array is accommodated in a microneedle system and comprises at least one reservoir and/or applicator.

15. The microneedle array for use according to claim 2, characterized in that the microneedles comprise a medicinal drug.

16. The microneedle array for use according to claim 2, characterized in that the color change indicator is at least one pH indicator, which is selected from the group consisting of nitrazine yellow, bromothytnol blue, carminic acid, brazilin, Congo red, neutral red, phenolphthalein, phenolic red, tetrabromophenolphthalein and a mixture thereof.

17. The microneedle array for use according to claim 4, characterized in that the color change indicator is nitrazine yellow or bromothymol blue.

18. The microneedle array for use according to claim 6, characterized in that the chromophores or fluorophores are neutral, acidic or basic methines, azomethines, triarylmethane dyes, indoamine dyes, natural dyes, or direct dyes thereof.

19. The microneedle array according to claim 1, characterized in that the color change indicator is biosensing ink.

20. The microneedle array according to claim 1, characterized in that the color change indicator detects peroxidases, which do not form part of the epidermis, by means of benzidines or phthalazines.

Description

EXAMPLE 1: VERIFICATION OF FUNCTIONALITY

[0058] Use of nitrazine yellow (pH indicator) for the delivery by means of microneedles. After successful delivery, a blue coloration is visible to the naked eye after approximately 10 seconds. The different pH value on the skin surface of pH 4 to 5.5 compared to the pH value of the stratum corneum of pH 6.5 to 7 allows a differentiated assessment of the penetration.

[0059] a) blue coloration indicates a successful delivery, that is, penetration of the microneedles into the stratum corneum;

[0060] b) the skin remains unchanged or takes on a slightly yellowish tint, that is, no successful penetration of the microneedles into the stratum corneum.

[0061] In this exemplary embodiment, minute amounts of nitrazine yellow (0.02%) were added as the indicator into the matrix of the microneedles.

EXAMPLE 2

[0062] Another exemplary embodiment is the use of color change indicators, which takes advantage of the presence of a substance available in the skin that, in contrast, is not present on the outer layer (epidermis).

[0063] Such a color change indicator can be made of one or more substance components. The presence and absence of a substance in the skin are to be understood to represent relative information and, with respect to a successful penetration into the skin, have to reach a distinguishing feature sufficient for the indicator.

[0064] Within the meaning of the invention, the use of a glucose-sensitive indicator is, in particular, an obvious choice, without being limited thereto. For this purpose, the reaction known for the detection of glucose in human bodily fluids can be utilized, in which the oxidation of glucose by glucose oxidase, and a subsequent reaction of the reaction products catalyzed by peroxidase, result in the color change of a substance subcomponent of the indicator.

[0065] Suitable substances for the differentiated assessment of a color change when the skin has been penetrated are preferably, but not exclusively, 3,3,5,5-tetramethylbenzidine (TMB/TMBH2) and derivatives derived from the structural class of the benzidines, as well as phthalazines, such as 5-amino-2,3-dihydrophthalazine-1,4-dione, and derivatives derived therefrom.

[0066] When using the leuco form of TMB or TMBH2 as the subcomponent of the indicator, the differentiated assessment of the penetration is accordingly made possible by the following: [0067] a) blue coloration indicates a successful delivery, that is, penetration of the microneedles into the stratum corneum; The change in color from TMBH2 (colorless) to TMB (blue) is based on the above-described reaction of the indicator. [0068] b) The skin remaining unchanged means no successful penetration of the microneedles into the stratum corneum and corresponding absence of the reaction of the indicator substances.