Methods for making microneedles using adjustment of component solubility in casting formulations
Methods are provided that involve the intentional and controlled precipitation of a drug or active agent, or a reduction of solubility of a polymer or other film-forming component of a formulation, or a combination of both methods, to improve the processes for making microneedles or other objects by casting into molds and the resulting parts produced by casting. The selective reduction in solubility of formulation components solves many problems associated with the casting of polymer formulations into molds. The methods are preferably adapted for making microneedles of biodegradable polymer and drug composites, and may also be used to produce other solid objects formed by casting into molds of compositions containing polymers and active agents.
1 . A method for making a microneedle, the method comprising:
preparing a casting solution which comprises at least one organic solvent and a polymer and, optionally, a substance of interest, wherein the polymer and the substance of interest, if present, are fully dissolved in the casting solution;
(i) adding a non-solvent for the polymer to the casting solution, and/or (ii) evaporating at least a portion of the at least one organic solvent, wherein the adding and/or evaporating are effective to reduce the effective molecular volume of the polymer in the casting solution; and then
casting the casting solution in a mold for the microneedle,
wherein the casting solution that is cast in the mold for the microneedle is the casting solution produced by the step of (i) adding the nonsolvent for the polymer to the casting solution, and/or (ii) evaporating the at least a portion of the at least one organic solvent, wherein the polymer in the casting solution that is cast has a concentration that is within 5% of the solubility limit of the polymer in a solvent system of the casting solution comprising the at least one organic solvent.
2 . The method of claim 1 , wherein the casting solution comprises a substance of interest, and wherein the adding a non-solvent to the casting solution and/or the evaporating at least a portion of the at least one organic solvent is/are effective to precipitate the substance of interest as a colloid or suspension in the casting solution.
3 . The method of claim 1 , wherein the casting comprises drying, centrifugation, and/or application of a vacuum to the casting solution in the mold.
4 . The method of claim 1 , wherein the at least one organic solvent comprises two different organic solvents.
5 . The method of claim 1 , wherein the mold is formed of silicone or another elastomer.
6 . The method of claim 5 , wherein the mold comprises a cavity having a microneedle tip portion and a funnel portion.
7 . The method of claim 6 , wherein the casting solution forms the microneedle tip portion, and the reduction of the effective molecular volume of the polymer is effective to avoid formation of a polymeric film on the funnel portion.
8 . The method of claim 1 , wherein the casting solution that is cast in the mold for the microneedle is the casting solution produced by the step of (i) adding a non-solvent for the polymer to the casting solution to precipitate the substance of interest as a colloid or suspension in the casting solution.
9 . The method of claim 1 , wherein the casting solution that is cast in the mold for the microneedle is the casting solution produced by the step of (ii) evaporating at least a portion of the at least one organic solvent to precipitate the substance of interest as a colloid or suspension in the casting solution.
10 . The method of claim 1 , wherein the casting solution that is cast in the mold for the microneedle is the casting solution produced by the step of (i) adding a non-solvent for the polymer to the casting solution, and (ii) evaporating at least a portion of the at least one organic solvent, to precipitate the substance of interest as a colloid or suspension in the casting solution.
11 . The method of claim 1 , wherein the polymer in the casting solution that is cast has a concentration that is within 1% to 2% of the solubility limit of the polymer in the solvent system of the casting solution comprising the at least one organic solvent.
12 . The method of claim 1 , wherein the microneedle is part of a microneedle array.
13 . The method of claim 1 , wherein the substance of interest is present in the casting solution and comprises a prophylactic or therapeutic agent.
14 . The method of claim 13 , wherein the polymer is a biodegradable polymer.
15 . The method of claim 14 , wherein the substance of interest comprises a contraceptive hormone.
16 . A method for making a microneedle, the method comprising the following ordered steps:
(i) preparing a casting solution which comprises at least one organic solvent and a polymer and a substance of interest, wherein the polymer is fully dissolved in the at least one organic solvent of the casting solution;
(ii) adding a non-solvent for the polymer to the casting solution in an amount effective to reduce the effective molecular volume of the polymer in the casting solution; and then
(iii) casting the casting solution in a mold for the microneedle, wherein the casting solution that is cast in the mold for the microneedle is the casting solution produced by the step of adding the non-solvent for the polymer to the casting solution.
17 . The method of claim 16 , wherein the mold comprises a cavity having a microneedle tip portion and a funnel portion, and wherein the casting solution forms the microneedle tip portion, and the reduction of the effective molecular volume of the polymer is effective to avoid formation of a polymeric film on the funnel portion.
18 . The method of claim 16 , wherein the adding the non-solvent for the polymer to the casting solution causes the substance of interest to precipitate as a colloid or suspension in the casting solution.
19 . The method of claim 16 , wherein the polymer in the casting solution that is cast has a concentration that is within 5% of the solubility limit of the polymer in the solvent system of the casting solution comprising the at least one organic solvent.
20 . The method of claim 16 , wherein the microneedle is part of a microneedle array.
21 . The method of claim 16 , wherein the substance of interest comprises a prophylactic or therapeutic agent.
22 . The method of claim 21 , wherein the polymer is a biodegradable polymer.
23 . The method of claim 22 , wherein the substance of interest comprises a contraceptive hormone.
24 . A method for making a microneedle, the method comprising the following ordered steps:
(i) preparing a casting solution which comprises at least one organic solvent and a polymer and a substance of interest, wherein the polymer is fully dissolved in the at least one organic solvent of the casting solution;
(ii) evaporating at least a portion of the at least one organic solvent in an amount effective to reduce the effective molecular volume of the polymer in the casting solution; and then
(iii) casting the casting solution in a mold for the microneedle, wherein the casting solution that is cast in the mold for the microneedle is the casting solution produced by the step of evaporating the at least a portion of the at least one organic solvent,
wherein the polymer in the casting solution that is cast has a concentration that is within 5% of the solubility limit of the polymer in the solvent system of the casting solution comprising the at least one organic solvent.
25 . A method for making a microneedle, the method comprising the following ordered steps:
(i) preparing a casting solution which comprises at least one organic solvent and a polymer and a substance of interest, wherein the polymer is fully dissolved in the at least one organic solvent of the casting solution;
(ii) evaporating at least a portion of the at least one organic solvent in an amount effective to reduce the effective molecular volume of the polymer in the casting solution; and then
(iii) casting the casting solution in a mold for the microneedle, wherein the casting solution that is cast in the mold for the microneedle is the casting solution produced by the step of evaporating the at least a portion of the at least one organic solvent,
wherein the evaporating at least a portion of the at least one organic solvent causes the substance of interest to precipitate as a colloid or suspension in the casting solution.
26 . The method of claim 25 , wherein the mold comprises a cavity having a microneedle tip portion and a funnel portion, and wherein the casting solution forms the microneedle tip portion, and the reduction of the effective molecular volume of the polymer is effective to avoid formation of a polymeric film on the funnel portion.
27 . The method of claim 25 , wherein the microneedle is part of a microneedle array.
28 . The method of claim 25 , wherein the substance of interest comprises a prophylactic or therapeutic agent.
29 . The method of claim 28 , wherein the polymer is a biodegradable polymer.
30 . The method of claim 29 , wherein the substance of interest comprises a contraceptive hormone.