Dosage forms with desired release profiles and methods of designing and making thereof

Abstract

In some aspects, the present disclosure provides dosage forms, such as oral drug dosage forms, configured to provide a desired release profile, the dosage forms comprising a multi-layered structure comprising a plurality of layers of a first erodible material admixed with a compound (e. g., a drug) or a reagent, wherein the first erodible material is embedded in a second material not admixed with the compound (e. g., the drug) or the reagent. In other aspects, the present disclosure provides methods of designing, such as obtaining a thickness and/or surface area of a layer comprising an erodible material admixed with a compound (e. g., a drug) or areagent, and/or amount of the compound (e. g., the drug) or the reagent admixed in the erodible material, and methods of making, such as three-dimensional printing, dosage forms configured to provide desired release profiles.

1 - 30 . (canceled) 
     
     
         31 : A drug dosage form comprising a multi-layered structure comprising a plurality of layers of a first erodible material admixed with a drug,
 wherein the multi-layered structure is embedded in a second material not admixed with the drug,   wherein each layer of the plurality of layers of the multi-layered structure has a top surface having a surface area,   wherein the surface area of the top surface of each layer of the multi-layered structure decreases sequentially based on the order, from top to bottom, in which each layer will be exposed to a bodily fluid,   wherein each layer of the plurality of layers of the multi-layered structure has a thickness and drug mass fraction (mF).   
     
     
         32 : The drug dosage form of  claim 31 , further comprising a top layer comprising an erodible material not admixed with the drug, wherein the top layer is positioned on top of a topmost layer of the multi-layered structure, and wherein a bottom surface of the top layer has a surface area that is the same or larger than the surface area of the top surface of the topmost layer of the multi-layered structure. 
     
     
         33 : The drug dosage form of  claim 32 , wherein the top layer has a thickness configured to delay the release of the drug from the drug dosage form for a desired amount of time. 
     
     
         34 : The drug dosage form of  claim 32 , wherein the erodible material of the top layer comprises the same material as the first erodible material. 
     
     
         35 : The drug dosage form of  claim 32 , wherein the erodible material of the top layer is different than the first erodible material. 
     
     
         36 : The drug dosage form of  claim 32 , wherein the top layer comprises another drug. 
     
     
         37 : The drug dosage form of  claim 31 , wherein two or more layers of the plurality of layers of the multi-layered structure have the same thickness. 
     
     
         38 : The drug dosage form of  claim 37 , wherein two or more layers of the plurality of layers of the multi-layered structure have a different drug mF. 
     
     
         39 : The drug dosage form of  claim 31 , wherein the second material is erodible. 
     
     
         40 : The drug dosage form of  claim 31 , wherein the second material is an insulating material that is impermeable to the bodily fluid, wherein the insulating material forms a barrier between the bodily fluid and at least a portion of the multi-layered structure. 
     
     
         41 : The drug dosage form of  claim 31 , wherein the multi-layered structure further comprises an intermediate layer comprising an erodible material not admixed with the drug, and wherein the intermediate layer is positioned between two layers of the plurality of layers of the multi-layered structure. 
     
     
         42 : The drug dosage form of  claim 41 , wherein the intermediate layer comprises the same material as the first erodible material. 
     
     
         43 : The drug dosage form of  claim 31 , further comprising one or more additional multi-layered structures. 
     
     
         44 : A drug dosage form comprising a multi-layered structure comprising a plurality of layers of a first erodible material admixed with a drug,
 wherein the multi-layered structure is embedded in a second material not admixed with the drug,   wherein each layer of the plurality of layers of the multi-layered structure has a top surface having a surface area,   wherein the surface area of the top surface of each layer of the multi-layered structure increases sequentially based on the order, from top to bottom, in which each layer will be exposed to a bodily fluid,   wherein each layer of the plurality of layers of the multi-layered structure has a thickness and drug mass fraction (mF).   
     
     
         45 : The drug dosage form of  claim 44 , further comprising a top layer comprising an erodible material not admixed with the drug, wherein the top layer is positioned on top of a topmost layer of the multi-layered structure, and wherein a bottom surface of the top layer has a surface area that is the same or larger than the surface area of the top surface of the topmost layer of the multi-layered structure. 
     
     
         46 : The drug dosage form of  claim 44 , wherein the second material is an insulating material that is impermeable to the bodily fluid, wherein the insulating material forms a barrier between the bodily fluid and at least a portion of the multi-layered structure. 
     
     
         47 : A drug dosage form comprising a multi-layered structure comprising a plurality of layers of a first erodible material admixed with a drug,
 wherein the multi-layered structure is embedded in a second material not admixed with the drug,   wherein each layer of the plurality of layers of the multi-layered structure has a top surface having a surface area,   wherein the plurality of layers of the multi-layered structure comprises, in sequential order, a first layer, a second layer, and a third layer,   wherein the first layer, the second layer, and the third layer are configured such that when the dosage form is exposed to a bodily fluid the top surface of the first layer will be exposed to the bodily fluid prior the top surface of the second layer, and the top surface of the second layer will be exposed to the bodily fluid prior to a top surface of the third layer,   wherein:
 (i) the top surface of the first layer and the top surface of the third layer have a larger surface area than the top surface of the second layer; or 
 (ii) the top surface of the first layer and the top surface of the third layer have a smaller surface area than the top surface of the second layer, and 
   wherein each layer of the plurality of layers of the multi-layered structure has a thickness and drug mass fraction (mF).   
     
     
         48 : The drug dosage form of  claim 47 , further comprising a top layer comprising an erodible material not admixed with the drug, wherein the top layer is positioned on top of a topmost layer of the multi-layered structure, and wherein a bottom surface of the top layer has a surface area that is the same or larger than the surface area of the top surface of the topmost layer of the multi-layered structure. 
     
     
         49 : The drug dosage form of  claim 48 , wherein the topmost layer of the multi-layered structure is the first layer. 
     
     
         50 : The drug dosage form of  claim 47 , wherein the second material is an insulating material that is impermeable to the bodily fluid, wherein the insulating material forms a barrier between the bodily fluid and at least a portion of the multi-layered structure.