Adare uses two physical processes simultaneously to create uniform droplets: piezoelectric vibration and a co-flowing non-solvent “carrier” stream. Other vibratory technologies fall short because the smallest achievable particle size is governed by the orifice diameter. For instance, in other vibratory processes, producing uniform 25 micrometer droplets requires machining a ~13 micrometer hole in a nozzle body. Such a small orifice does not allow passage of viscous solutions or concentrated suspensions, fouls easily after a small number of uses, and is not a scalable approach. This is why all other scaleable uniform microsphere technologies are limited to a size of ~ 150 micrometers. Conversely, Adare’s process allows production of those same 25 micrometer particles (and much smaller) with sufficiently large orifice diameters. Not to mention, Adare can achieve the same small sizes with a shell layer..

In Figure A, uses a two- or three- fluid vibrating nozzle with co-flowing axial “carrier” stream used to reduce jet diameter; the use of both physical mechanisms simultaneously is patent-protected. For any given mass flow rate, droplet size can be reduced simply by increasing the frequency of vibration. In Stratµm™ technology, the carrier stream is comprised of water, which is analogous to emulsion processes. In Optimµm® technology, the carrier stream is comprised of air or nitrogen, which is analogous to spray congealing or prilling.

In Figure B, three-fluid nozzle adds further control over particle architecture by adjustment of “core” and “shell” flow rates, in addition to vibratory frequency. Not to mention, the compatibility with a wide range of excipients and particle sizes enables unique functionality and product opportunities for creating first-in-class prescription formulations or matching complex modified release profiles of over-the-counter products.

The Precision Particle Fabrication™ platform was developed with industry in mind. It delivers on the promise of precision microparticles at a previously unachievable scale. Scaled multi-nozzles have been developed for two- and three-stream flow for producing solid microspheres (Figure A) and core-shell microcapsules (Figure B). The platform technology has been divided into three subcategories: Stratµm™, Optimµm®, and Unisun®.

Stratµm™

• Particle sizes down to 10 μm with ± 5% deviation from the mean diameter
• Uses a water “carrier” stream
• Analogous to emulsion processes
• Requires lyophilization
• Compatible with PLGAs, PLAs, PCLs, PCPHs, alginates, gelatins, and other biopolymers
• Good for injectable small molecules, proteins, peptides, vaccines, and heat-labile molecules

Optimµm®

• Particle sizes down to 75 μm with Span values as low as 0.40
• Uses a nitrogen “carrier” stream
• Analogous to spray congealing
• No drying step or coating required
• Compatible with waxes, lipids, stearates, gelatins
• Good for oral small molecules, nutraceuticals, agricultural applications, flavorings, and heat stable molecules

Unisun®

• Combines Stratµm™ microspheres with a film forming agent, or film-forming agent alone
• Film-forming agent uses a non-irritating aqueous base
• Film-forming agent dries quickly on warm biological surfaces
• Can be used to inject and set up highly concentrated depots of a drug
• Good for small molecules, proteins, peptides, and vaccines

Scale-up and Manufacturing

Our platform technologies have been scaled from single nozzles to variations of multi-nozzles, then another order of magnitude by simply running multi-nozzles in parallel. Housed in Class 100,000 (ISO 8) production suite pictured below, is the capability to produce cGMP Optimµm® product at the 100 g – 200 g scale, and at the 4 kg – 30 kg scale, for solid oral dosage forms. Additional capability includes assay and impurity quantification for encapsulated pharmaceutical ingredients, and design services to help partners design, build, qualify, use, and maintain their own manufacturing systems.