METHODS FOR MANUFACTURING MICROPROJECTION ARRAYS
Methods for the manufacture of a microprojection array are provided. In the methods, a formulation is introduced into cavities of a microprojection array mold by means that achieve a uniform amount of formulation retained in each cavity.
1 . A method of forming a microprojection array, comprising:
(a) dispensing a quantity of a formulation comprising a polymer, a therapeutic agent and a solvent on a mold having a plurality of cavities corresponding to microprojections in a microprojection array,
(b) transferring formulation into the plurality of cavities;
(c) removing excess formulation from the mold in a manner that retains formulation in each of the plurality of cavities; and
(d) drying the formulation to remove the solvent to form the resulting array.
2 . The method of claim 1 , further comprising:
covering the formulation on the mold with a substrate; and
after step (c), disengaging the mold from the covering in a manner that retains formulation in each of the plurality of cavities.
3 . The method of claim 2 , wherein the substrate is a cover slip.
4 . The method of claim 1 , wherein removing excess formulation comprises wiping the mold with a wiper.
5 . The method of claim 1 , wherein said transferring comprises transferring formulation into the plurality of cavities by applying pressure to the substrate when in contact with the formulation dispensed on the mold.
6 . The method of claim 1 , wherein said transferring comprises pressurizing the mold.
7 . The method of claim 6 , wherein the mold is pressurized to 50 psi.
8 . The method of claim 1 , wherein said transferring comprises applying a vacuum to the mold.
9 . The method of claim 1 , further comprising:
dispensing a basement layer on the mold surface; and
drying the basement layer.
10 . The method of claim 9 , further comprising:
affixing the basement layer to a backing.
11 . The method of claim 1 , further comprising:
demolding the microstructure array.
12 . The method of claim 1 , wherein disengaging the mold achieves a uniform retention of formulation in each array, as evidenced by a standard deviation in amount of formulation retained in each array less than or equal to about 10% of the average amount of formulation retained in the array.
13 . The method of claim 1 , wherein the therapeutic agent is selected from a drug, a small molecule, a peptide or protein, or a vaccine.
14 . The method of claim 1 , further comprising:
prior to step (a), dissolving or suspending the at least one therapeutic agent and the at least one polymer in a solvent to form the formulation.
15 . The method of claim 14 , wherein the solvent is water.
16 . The method of claim 14 , wherein the formulation further comprises at least one sugar.
17 . The method of claim 16 , wherein the sugar is selected from sorbitol, sucrose, trehalose, fructose, or dextrose.
18 . The method of claim 14 , wherein the formulation further comprises a surfactant.
19 . The method of claim 14 , wherein the formulation further comprises an antioxidant.
20 . The method of claim 19 , wherein the antioxidant is selected from methionine, cysteine, D-alpha tocopherol acetate, EDTA, or vitamin E.