Separable microneedle arrays for sustained release of drug

Abstract

Separable microneedle arrays and microneedle patches are provided that may achieve sustained release of drug. The microneedle arrays may include one or more features that facilitate separation of the microneedles, such as a bubble structure. The microneedle arrays may include an effervescent material.

We claim: 
     
         1 . A microneedle array for administering a substance of interest into a patient's biological tissue, the microneedle array comprising:
 a base substrate having a microneedle side and an opposing back side;   two or more solid microneedles extending from the base substrate, wherein at least a tip end portion of each microneedle comprises a substance of interest,   wherein a bubble structure is at or near a base end of each of the two or more solid microneedles to facilitate separation of at least the tip end portion of each microneedle from the base substrate after the two or more solid microneedles penetrate into the patient's biological tissue.   
     
     
         2 . The microneedle array of  claim 1 , wherein the bubble structures are at an interface of each of the two or more microneedles and a funnel portion extending from the microneedle side of the base substrate. 
     
     
         3 . The microneedle array of  claim 1 , wherein the substance of interest comprises an active pharmaceutical ingredient. 
     
     
         4 . The microneedle array of  claim 3 , wherein the active pharmaceutical ingredient comprises a contraceptive hormone. 
     
     
         5 . The microneedle array of  claim 4 , wherein the contraceptive hormone comprises a progestin. 
     
     
         6 . The microneedle array of  claim 3 , wherein the microneedle array is configured to release a therapeutically or prophylactically effective amount of the active pharmaceutical ingredient to the patient for a sustained period of at least 2 weeks. 
     
     
         7 . The microneedle array of  claim 3 , wherein the microneedle array is configured to release a therapeutically or prophylactically effective amount of the active pharmaceutical ingredient to the patient for a sustained period of at least 4 weeks. 
     
     
         8 . The microneedle array of  claim 1 , wherein the two or more solid microneedles are formed of a composition comprising a first matrix material in which the substance of interest is dispersed. 
     
     
         9 . The microneedle array of  claim 8 , wherein the first matrix material comprises poly-lactic acid, poly-lactic glycolic acid, or a combination thereof. 
     
     
         10 . The microneedle array of  claim 8 , wherein the two or more solid microneedles each further comprises a secondary funnel portion which comprises a second matrix material different from the first matrix material. 
     
     
         11 . The microneedle array of  claim 10 , wherein the second matrix material comprises polyvinylpyrrolidone, polyvinyl alcohol, a carbohydrate, or a combination thereof. 
     
     
         12 . The microneedle array of  claim 11 , wherein the carbohydrate comprises sucrose. 
     
     
         13 . The microneedle array of  claim 1 , wherein the two or more microneedles have a length of about 200 μm to about 1200 μm and the secondary funnel portions comprise a straight, tapered sidewall. 
     
     
         14 . The microneedle array of  claim 1 , wherein the separation of the at least the tip portion of each microneedle comprises (i) application of a force effective to fracture the bubble structure, and/or (ii) dissolution of a wall material of the bubble structure. 
     
     
         15 . A microneedle array for administering a substance of interest into a patient's biological tissue, the microneedle array comprising:
 a base substrate having a microneedle side and an opposing back side;   at least one primary funnel portion extending from the microneedle side of the base substrate; and   two or more solid microneedles extending from the at least one primary funnel portion, wherein the two or more solid microneedles comprise a substance of interest and a secondary funnel portion extending from the at least one primary funnel;   wherein the two or more solid microneedles are configured to penetrate into the patient's biological tissue under compression and then to separate from the secondary funnel portions, and   wherein each of the two or more solid microneedles comprises a bubble structure which facilitates separation of the two or more microneedles from the secondary funnel portions.   
     
     
         16 . The microneedle array of  claim 15 , wherein the two or more solid microneedles are configured to release a therapeutically or prophylactically effective amount of the substance of interest to the patient for a sustained period of at least 1 week. 
     
     
         17 . The microneedle array of  claim 15 , wherein the microneedle array is configured to release the therapeutically or prophylactically effective amount of the substance of interest to the patient for a sustained period of at least 4 weeks. 
     
     
         18 . The microneedle array of  claim 15 , wherein the two or more solid microneedles are formed of a composition comprising a matrix material in which the substance of interest is dispersed. 
     
     
         19 . The microneedle array of  claim 18 , wherein the matrix material comprises poly-lactic acid, poly-lactic glycolic acid, or a combination thereof. 
     
     
         20 . A microneedle patch comprising:
 the microneedle array of  claim 15 ;   an adhesive layer; and   a handle layer affixed to the base substrate, wherein the handle layer comprises a tab portion which extends laterally away from a single side of the two or more solid microneedles and permits a person to manually hold the tab portion to manipulate the patch without contacting the two or more solid microneedles.   
     
     
         21 . A microneedle array for administering a substance of interest into a patient's biological tissue, the microneedle array comprising:
 a base substrate having a microneedle side and an opposing back side;   a primary funnel portion extending from the microneedle side of the base substrate; and   microneedles extending from the primary funnel portion, wherein at least a tip end portion of each microneedle comprises a substance of interest,   wherein a bubble structure is disposed at or near a base end of each of the microneedles, and the microneedles are configured to penetrate into the patient's biological tissue under compression and then to separate from the primary funnel portion by fracture at the bubble structure.   
     
     
         22 . A method of administering a substance of interest to a patient, comprising:
 inserting into a biological tissue of the patient the microneedles of the array of microneedles of  claim 1 ;   separating at least the tip end portions of the microneedles from the base substrate; and   releasing the substance of interest, from the separated at least tip end portions of the microneedles, into the biological tissue.   
     
     
         23 . The method of  claim 22 , wherein:
 the biological tissue comprises skin,   the substance of interest comprises an active pharmaceutical ingredient, and   the inserted microneedles release a therapeutically or prophylactically effective amount of the active pharmaceutical ingredient into the patient for a sustained period of at least 1 week.   
     
     
         24 . The method of  claim 23 , wherein the active pharmaceutical ingredient comprises a contraceptive hormone. 
     
     
         25 . The method of  claim 24 , wherein the contraceptive hormone comprises a progestin. 
     
     
         26 . The method of  claim 22 , wherein the separation comprises fracture of a bubble structure by application of a shear force to the microneedle array. 
     
     
         27 . The method of  claim 26 , wherein the shear force is applied between 1 second and 60 seconds following the insertion of the microneedles.