Aron H. Blaesi

• Massachusetts Institute of Technology

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-d...

Recently, we have shown in dogs that the gastric residence time of expandable fibrous dosage forms can be prolonged by a strengthening enteric coating on the fibers. In this work, the effect of the volume fraction of the coating, φc, on the expansion, mechanical properties, and gastric residence time in pigs is investigated. Three methacrylic acid-...

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. Pres...

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 o...

The expandable, gastroretentive dosage forms are promising for precise control of drug concentration in blood. So far, however, short gastric retention times and safety considerations have precluded their use. In this work, to mitigate the above limitations, expandable fibrous dosage forms were investigated for mechanical strength and gastric reten...

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 qualit...

In this work, the rates of expansion and drug release by fibrous dosage forms with two excipients are investigated for prolonged delivery of sparingly soluble drugs. The formulation consisted of ibuprofen drug, high-molecular-weight hydroxypropyl methyl cellulose (HPMC) excipient, and the enteric methacrylic acid-ethyl acrylate excipient. Upon imme...

In this work, drug release by highly drug-loaded, densely-packed fibrous dosage forms is investigated. The formulations consisted of 87wt% ibuprofen drug and 13wt% hydroxypropyl methyl cellulose (HPMC) excipient of molecular weights 10, 26, or 86 kg/mol. The dosage forms were prepared by 3D-patterning a drug-excipient-water paste in a cross-ply arr...

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...

In part 1, we have investigated solid-solution single fibers of a sparingly-soluble drug (ibuprofen) and a highly-soluble excipient (67 wt% hydroxypropyl methyl cellulose (HPMC) and 33 wt% polyoxyl stearate (POS)). In this part, 3D-micro-patterned fibrous dosage forms of the same formulation are tested and modeled. Upon immersion in a small volume...

Many drug therapies could be greatly improved by dosage forms that reside in the stomach for prolonged time and release the drug slowly. In this work, therefore, fibrous dosage forms that expand rapidly in the gastric fluid to prevent their passage into the intestines are investigated. The dosage forms consisted of acetaminophen drug and a high-mol...

Solid solutions of sparingly water-soluble drugs and highly water-soluble excipients are widely used for enhancing the drug delivery rate into the blood stream. The basic physico-chemical mechanisms, however, are not well understood. To delineate the mechanisms, therefore, in this work solid-solution fibers are immersed in a small volume of dissolu...

Recently, we have introduced fibrous dosage forms prepared by 3D-micro-patterning of drug-laden viscous melts. Such dosage forms enable predictable microstructures and increased drug release rates, and they can be manufactured continuously. However, melt processing is not applicable if the melting temperature of the formulation is greater than the...

Objectives: To test the safety of a novel miniaturized device that produces nitric oxide (NO) from air by pulsed electrical discharge, and to demonstrate that the generated NO can be used to vasodilate the pulmonary vasculature in rabbits with chemically-induced pulmonary hypertension. Study design: A miniature NO (mini-NO) generator was tested...

Recently, we have introduced fibrous dosage forms prepared by the predictable deposition, or 3D-micro-patterning, of a drug-laden fibrous melt on a surface. Such dosage forms enable precisely controlled microstructures and drug release rates, and can be manufactured by an efficient, continuous melt process. However, the applicability of melt-proces...

At present, the most prevalent pharmaceutical dosage forms, the orally-delivered immediate-release tablets and capsules, are porous, granular solids. They disintegrate into their constituent particulates upon ingestion to release drug rapidly. The design, development, and manufacture of such granular solids, however, is inefficient due to difficult...

Rationale: Inhalation of nitric oxide (NO) produces selective pulmonary vasodilation and is an effective therapy for pulmonary hypertension in term hypoxic newborns. However, NO inhalation therapy is expensive and the cylinder delivery system of NO gas is complicated. NO therapy involves heavy gas cylinders (45 kg) and a complex delivery device, ga...

Nitric Oxide Produced in a Miniaturized Endotracheal Injector by Pulsed Electrical Discharge Induces Pulmonary Vasodilation in Rabbits

In recent studies, we have introduced melt-processed polymeric cellular dosage forms to achieve both immediate drug release and predictable manufacture. Dosage forms ranging from minimally-porous solids to highly porous, open-cell and thin-walled structures were prepared, and the drug release characteristics investigated as the volume fraction of c...

The most prevalent pharmaceutical dosage forms at present are granular solids in the form of oral tablets and capsules. While effective in releasing drug rapidly upon contact with gastrointestinal fluid, their manufacture, which relies on particulate processing, is fraught with difficulties associated with the unpredictable inter-particle interacti...

Inhalation of nitric oxide (NO) produces selective pulmonary vasodilation without dilating the systemic circulation. However, the current NO/N2 cylinder delivery system is cumbersome and expensive. We developed a lightweight, portable, and economical device to generate NO from air by pulsed electrical discharge. The objective of this study was to i...

At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and possess adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Predictable manufacture, however, could be achieved by liquid-based proc...

The most prevalent pharmaceutical dosage forms at present––the oral immediate-release tablets and capsules––are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liqui...

The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are...

Inhalation of nitric oxide (NO) produces selective pulmonary vasodilation and is an effective therapy for treating pulmonary hypertension in adults and children. In the United States, the average cost of 5 days of inhaled NO for persistent pulmonary hypertension of the newborn is about $14,000. NO therapy involves gas cylinders and distribution, a...

Pharmaceutical manufacturing has traditionally been considered largely a matter of regulatory compliance. Consequently, it has been inefficient, but it is now increasingly being recognized as an opportunity for cost reduction. Recent initiatives by regulatory authorities, and by the industry, aim at easing regulations and encouraging process innova...

Optimization and characterization of glucose electrooxidizing catalysts for electrochemical continuous glucose sensors and glucose fuel cells has been subject to numerous investigations. Currently, the most advanced catalyst technologies for glucose electrooxidation are enzyme supported. These catalysts show good selectivity and activity towards th...