Other

The General Hospital Corporation

Aron H Blaesi

Nannaji Saka

Warren M Zapol

Binglan Yu

Matt Hickcox

By the ingestion of dosage forms containing sparingly water-soluble drug particles, it is not possible to deliver drug into the blood stream at high rates, because the drug dissolution rate, and the absorption rate, are limited by solubility. Herein, therefore, dosage forms comprising a slender, three-dimensional structural framework of sparingly-soluble drug dissolved in an excipient matrix comprising at least a water-soluble polymer carrier and an amphiphilic polymer are disclosed. Upon immersion in a physiological fluid, said fluid wets the structural framework, interdiffuses with it, and the amphiphilic polymer self-assembles as micelles, thereby enhancing drug solubility. Concomitantly, the framework erodes and rapidly releases drug molecules, thus enhancing drug concentration in the fluid and the drug delivery rate into the blood stream.

Dosage form comprising structured solid-solution framework of sparingly-soluble drug and method for manufacture thereof

Recently, we have introduced 3D-micro-patterned pharmaceutical dosage forms for enhancing the efficacy, safety, convenience, and cost-effectiveness of drug therapies. Presented herein are an apparatus and a method for the manufacture of such dosage forms. The apparatus comprises at least a first extruder and at least a second extruder. The first extruder comprises an extruder channel having an exit port with a valve mated to an input port of a second extruder. Said second extruder comprises a translatable piston for extruding plasticized fiber at controlled speed. The apparatus further comprises a stage movable at the controlled speed of the extruded fiber for depositing said fiber to a three dimensional structural framework. The method includes extruding plasticized matrix from a first extruder into a second extruder, extruding said plasticized matrix from the second extruder through a fiber fabrication exit port at controlled speed to form extruded fiber, and depositing said extruded fiber onto a fiber assembling stage to form a three dimensional structural framework.

Method for 3D-micro-patterning

In this specification, a method for the manufacture of solid dosage forms is disclosed. The method includes extruding a plasticized matrix through an exit port of an extrusion channel to form one or more plasticized fibers, structuring said fibers to a three dimensional structural network by patterning on a translating or rotating stage, and solidifying the patterned structure.

Method for the manufacture of solid dosage forms

In this specification, a pharmaceutical dosage form comprising a three-dimensional structural framework of thin, solid elements surrounded by interconnected void space is disclosed. The elements comprise at least a drug, a water-absorptive, polymeric excipient, and a hydrophilic surface composition. Upon immersion in a dissolution fluid the three-dimensional structural framework is wetted uniformly, transitions from solid to viscous due to the diffusion of dissolution fluid into the thin elements, expands in all dimensions, and disintegrates and releases drug. The disclosed dosage form enables greater drug delivery rates and better control of the drug concentration in blood for improving the efficacy and safety of drug therapies.

Expandable structured dosage form for immediate drug delivery

The present disclosure provides systems and method for electric plasma synthesis of nitric oxide. In particular, the present disclosure provides a nitric oxide (NO) generation system configured to produce a controllable output of therapeutic NO gas at the point of care.

Delivery systems and methods for electric plasma synthesis of nitric oxide

The most prevalent pharmaceutical dosage forms at present, the oral-delivery tablets, are granular solids. An inherent limitation of such granular solids for drug release applications is the unpredictability of the microstructure. As a result, the drug release rate and other properties are difficult to control, and their range is also limited. Presented herein, therefore, is a solid dosage form with predictable microstructure and properties. The dosage form includes a drug-containing solid comprising a three dimensional structural framework of one or more two-dimensional structural elements or sheets.

Dosage form comprising structural framework of two-dimensional elements

Recently, we have introduced fibrous dosage forms that enable predictable microstructures with a greater range of pharmaceutically relevant properties. Presented herein, accordingly, is a method for the manufacture of such fibrous dosage forms. The method includes extruding a plasticized matrix through an exit port of an extrusion channel to form one or more plasticized fibers, structuring said fibers to a three dimensional structural network by patterning on a translating or rotating stage, and solidifying the patterned structure.

Method for the manufacture of fibrous dosage forms

At present, the most prevalent pharmaceutical dosage forms, the oral immediate-release tablets and capsules, are granular solids. The problem of such solids is that their microstructure and properties are not predictable from physical models. As a consequence, product development and manufacture are resource-intensive and time-consuming, and quality control is statistical by testing instead of by design. Furthermore, the range of the drug release rate, and the variety of active ingredients that can be processed to a functional product, are limited in such dosage forms. Presented herein, accordingly, is a fibrous dosage form suitable for immediate-release applications prepared by a predictable liquid-based process. The fibrous dosage form includes a drug-containing solid comprising a three dimensional structural network of one or more drug-containing fibers.

Fibrous dosage form

Recently, we have introduced fibrous dosage forms that enable predictable microstructures with a greater range of pharmaceutically relevant properties. Presented herein, accordingly, are a method and an apparatus for the manufacture of such fibrous dosage forms. The method includes extruding a plasticized matrix through an exit port of an extrusion channel to form at least one plasticized fiber, and structuring said at least one plasticized fiber to a three dimensional structural network of fibers. The apparatus includes an internally hollow housing defining an extrusion channel, a conveying element for extruding a plasticized matrix in the extrusion channel through an exit port to form at least one plasticized fiber, and a unit for structuring said at least one plasticized fiber to a three dimensional structural network of fibers.

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Cambridge, MA, United States of America

Aron H Blaesi