System for manufacturing controlled release dosage forms, such as a zero-order release profile dosage form manufactured by three-dimensional printing

A dosage form comprising:

• a first end cap;
• a second end cap spaced apart from the first end cap;
• and
• a first region extending from the first end cap to the second end cap, comprising a first regional concentration of at least one Active Pharmaceutical Ingredient, which concentration may be zero;
• and
• one or more additional regions extending from the first end cap to the second end cap and surrounding the first region and any other region located interiorly of it, at least one of the additional regions having a respective non-zero regional concentration of at least one Active Pharmaceutical Ingredient which is different from the regional concentration in any region adjacent to the region,
• wherein, upon exposure to a liquid, the regions have respective regional recession rates and the end caps have an end cap recession rate which is substantially slower than any of the regional recession rates.

A method of making a dosage form, comprising:

• spreading a layer of powder;
• depositing at least one binder liquid onto the powder in specified places, which binder liquid may contain at least one Active Pharmaceutical Ingredient;
• and
• repeating, the above steps as many times as needed;
• wherein the repeated depositing is performed so as to create an innermost region, the innermost region having a concentration of at least one Active Pharmaceutical Ingredient, which concentration may be zero, and at least one additional region, each additional region surrounding the innermost region and any other regions interiorly of the region, each additional region having a respective concentration of at least one Active Pharmaceutical Ingredient which is different from the concentration in adjacent regions.

A method of making a dosage form, comprising:

• spreading a layer of a first powder;
• depositing an end cap binder liquid onto the first powder;
• repeating the above steps as many times as needed to make an end cap;
• spreading a layer of a second powder;
• depositing at least one binder liquid onto the powder in specified places, which binder liquid may contain at least one Active Pharmaceutical Ingredient;
• repeating, the above steps as many times as needed;
• spreading a layer of the first powder;
• depositing end cap binder liquid onto the first powder;
• repeating the above steps as many times as needed to make an end cap;
• and
• harvesting the dosage form;
• wherein the repeated depositing of binder liquids is performed so as to create an innermost region, the innermost region having a concentration of at least one Active Pharmaceutical Ingredient, which concentration may be zero, and at least one additional region, each additional region surrounding the innermost region and any other regions interiorly of the region, each region having a respective non-zero concentration of at least one Active Pharmaceutical Ingredient which is different from the concentration in adjacent regions.

A method of designing a dosage form to provide release of at least one Active Pharmaceutical Ingredient in a desired release profile, comprising:

• selecting a material set;
• determining a surface recession rate or Active Pharmaceutical Ingredient release rate for the selected material set when exposed to a liquid;
• estimating a design of regions, each region having respective dimensions and having a respective regional concentration of the at least one Active Pharmaceutical Ingredient;
• calculating a predicted release profile of the at least one Active Pharmaceutical Ingredient;
• comparing the predicted release profile to the desired release profile;
• and
• adjusting a dimension or concentration or both in some layers to obtain a predicted release profile which matches the desired release profile to a desired closeness.