Formulation of drugs and vaccines in the form of percutaneous injectable needles
The invention relates to percutaneous administration of drugs and vaccines in form of solid penetrating needles, “injectable needles”, comprising a polymeric matrix resulting from the polymerization of a polymerizable paste or mixture. The injectable needles are hard enough to penetrate the skin and can be administered percutaneously by simple pusher or injector delivery devices. The manufacturing procedure of the injectable needles allows for the incorporation of the drug as preformulated stable microparticles and incorporation of modifying agents to modulate stiffness, solubility and drug release. Drugs formulated in these injectable needles offer a safe, simple and effective alternative to conventional percutaneous drug delivery systems based on hypodermic needles and syringes that require refrigerated storage and reconstitution prior to administration.
1. An injectable needle, with a diameter ranging from 0.2 to 2 mm, comprising:
a) 30% to 90% in mass of a solid polymeric matrix continuous phase having a flexural strength over 10 MPa and comprising (i) an addition polymer formed by the polymerization of addition monomers, wherein the addition polymer is selected from the group consisting of polycyanoacrylates, polyacrylates, polymethacrylates, polyvinyls, and any combination thereof, and (ii) a polymeric modifying agent selected from the group consisting of polylactides, polyglycolides, polylactide-co-glycolides or polyvinylpyrrolidones, and any combination thereof, wherein the polymeric matrix is at least partially biodegradable or resorbable, and
b) a solid discontinuous water-soluble phase containing a drug preformulated as particles or granules having a diameter between about 0.02 and about 500 microns, the solid discontinuous water-soluble phase in direct contact with the solid polymeric matrix,
wherein the injectable needle is formed within a mold by polymerization of the addition monomers in the presence of the polymeric modifying agent to form an interpenetrating polymeric network (IPN) that incorporates the solid discontinuous water-soluble phase.
2. The injectable needle of claim 1 , wherein the polyacrylate is selected from: polyacrylic acid, polyacrylamide, poly-N-isopropylacrylamide, alkaline polyacrylate, alcaline-terreus polyacrylate, ammonium polyacrylate, or any of their combinations.
3. The injectable needle of claim 1 , wherein the polymethacrylate is selected from: polymethacrylic acid, alkaline polymethacrylate, alkaline-terreous polymethacrylate, ammonium polymethacrylate, 2-hydroxypropyl polymethacrylate, (2-dimethylamino)ethylpolymethacrylate, 1-glycerol polymethacrylate, polymethacrylamide, or any of their combinations.
4. A method for the manufacture of the injectable needle of claim 1 which comprises:
a.) mixing the addition monomers and the polymeric modifying agent with the solid discontinuous water-soluble phase containing the drug, preformulated as particles or granules having a diameter between about 0.02 and about 500 microns to form a paste, and
b.) polymerizing the resulting paste within a mold to form an injectable needle having an interpenetrating polymeric network (IPN) that incorporates the solid discontinuous water-soluble phase containing the drug particles or granules having a diameter between about 0.02 and about 500 microns, wherein:
(i) the injectable needle has a diameter ranging from 0.2 to 2 mm and comprises 30% to 90% in mass of a solid polymeric matrix continuous phase having a flexural strength over 10 MPa and comprising an addition polymer formed by the polymerization of the addition monomers, wherein the addition polymer is selected from the group consisting of polycyanoacrylates, polyacrylates, polymethacrylates, polyvinyls, and any combination thereof, and (ii) a polymeric modifying agent selected from the group consisting of polylactides, polyglycolides, polylactide-co-glycolides or polyvinylpyrrolidones, and any combination thereof, wherein the polymeric matrix is at least partially biodegradable or resorbable, and
(ii) the solid discontinuous water-soluble phase is in direct contact with the solid polymeric matrix continuous phase.
5. The method of claim 4 , wherein the polymerization reaction is a polyaddition reaction that is catalysed photochemically.
6. A method for percutaneous administration of a drug for the treatment, prevention or diagnosis of a human or animal disease which comprises:
providing an animal or human in need of said drug and
administering said drug to the animal or human by the injectable needle of claim 1 .