Pyramidal microneedles with enhanced drug loading capacity and method for manufacturing
View Patent ↗The present invention provides a solution to increase the drug loading capacity and drug delivery precision of dissolving microneedles. These solutions include: (a) increasing the base of the microneedle cavities without substantially changing the microneedle's height and geometry, (b) use of drug suspension and (c) a specific centrifugation order for filling drug and matrix material. In the first preferred embodiment, a microneedle master mould comprising a plurality of microneedles, wherein each of the microneedles further comprising a chamfered base which extends to and adjoins with its neighboring chamfered bases is provided. In the second preferred embodiment, a method of making dissolving microneedles is provided, comprising (a) providing a microneedle template comprising a plurality of microneedle cavities, wherein each of the microneedle cavities further comprising a chamfered base which extends to and adjoins with its neighboring chamfered bases; (b) dispensing a drug suspension in the substrate cavity on the microneedle template; (c) centrifuging the microneedle template which is loaded with a drug suspension, (d) dispensing a matrix material solution in the substrate cavity on the microneedle template; (d) centrifuging the microneedle template loaded with the drug suspension and the matrix material solution; and (e) drying the centrifuged microneedle template in a controlled environment.
1 . A method of manufacturing dissolving microneedles, the method comprising:
a. Providing a microneedle template, the microneedle template comprising a plurality of pyramidal microneedle cavities, immediately under each pyramidal microneedle cavity is incorporated with a chamfered base which extends to and adjoins with its neighboring chamfered bases, wherein the extending and adjoining of the chamfered bases eliminates any horizontal substrate area between the microneedle cavities,
b. Preparing a suspension made of a drug and loading the template with said suspension,
c. Centrifuging the loaded microneedle template to fill the microneedle cavities with the drug suspension, and causing the drug suspension to completely settle to the bottom of the microneedle cavities,
d. Loading a matrix material solution on the template, and
e. Centrifuging the loaded microneedle template to fill the microneedle cavities with the matrix material solution.
2 . The method for manufacturing dissolving microneedles according to claim 1 , wherein in step c, the loaded microneedle template is subjected to a centrifugation process at 5000 rpm for 5 minutes.
3 . The method of manufacturing dissolving microneedles according to claim 1 , further comprising a drying step that places the microneedle template in a controlled environment for drying.
4 . The method of manufacturing dissolving microneedles of claim 3 , wherein the controlled environment for drying involves centrifugation.
5 . The method of manufacturing dissolving microneedles according to claim 1 , wherein the drug suspension comprises insoluble drug particles in water.
6 . The method for manufacturing dissolving microneedles according to claim 1 , wherein the matrix material is made of sodium hyaluronate, polyvinylpyrrolidone, carboxymethyl cellulose or any combination thereof.
7 . The method of manufacturing dissolving microneedles of claim 3 , wherein the controlled environment involves a temperature range of 15-30 degrees Celsius, a relative humidity range of 30%-50% at atmospheric pressure.
8 . The method of claim 4 , wherein the centrifugation is performed in a temperature range of 0-20 degrees Celsius.
9 . The method of manufacturing dissolving microneedles according to claim 1 , wherein the microneedle template is made of an elastomeric material.
10 . The method of manufacturing dissolving microneedles according to claim 1 , wherein the microneedle template is made of silicon material.
11 . The method of claim 1 , wherein the chamfered base of the pyramidal microneedle cavities is made of a straight surface.
12 . The method of claim 1 , wherein the chamfered base of the pyramidal microneedle cavities is made of a curved surface.
13 . A microneedle master mold for manufacturing the microneedle template of claim 1 , comprising:
a. a metal base,
b. a plurality of pyramidal microneedles, the plurality of pyramidal microneedles is formed by engraving on the surface of the metal base,
c. a plurality of isosceles throughs, wherein one isosceles through is engraved between the feet of two adjacent pyramidal microneedles, the isosceles troughs surrounding each pyramidal microneedle forming a chamfered base immediately under each pyramidal microneedle thereby eliminating the horizontal substrate area between the adjacent microneedles.
14 . The microneedle master of claim 13 , wherein the chamfered base is made of a straight surface.
15 . The microneedle master of claim 13 , wherein the chamfered base is made of a curved surface.
16 . The microneedle master mold according to claim 13 , wherein the size of the isosceles trough is: the base of the isosceles trough is 300 m, and the depth of the isosceles trough is 50 m-500 m.
17 . The microneedle master mold of claim 16 , wherein the depth of the isosceles trough is 50 μm-200 μm.
18 . A method for making the microneedle master mold of claim 13 ,
a. First, a plurality of pyramidal microneedles is carved on the surface of a metal block;
b. Then, one isosceles trough is carved between the feet of the adjacent pyramidal microneedles; the method of carving the isosceles grooves involves conventional physical removal process such as grinding, milling, electro-discharge machining, laser machining steps;
Wherein the isosceles troughs are carved in two orthogonal directions on the surface of the metal block, thereby incorporating four chamfered surfaces immediately under each pyramidal microneedle to eliminate the horizontal substrate area between the adjacent microneedles.
19 . The method of claim 18 , wherein the size of the isosceles trough is: the base of the isosceles trough is 300 μm, and the depth of the isosceles trough is 50 μm-500 μm.
20 . The method of claim 19 , wherein the depth of the isosceles trough is 50 μm-200 μm.