New Jersey Institute of Technology

Other

US Government As Represented by the Secretary of the Army

Rutgers, the State University of New Jersey

Rajesh N Dave

Robert Pfeffer

Ecevit A Bilgili

Daniel To

Anagha A Bhakay

Costas George Gogos

Ming-Wan Young

Jose A Quevedo

Qun Yu

Mohammad Azad

Stanislav S Dukhin

Fernando J Muzzio

Peter Bonnett

Satoru Watano

Chao Zhu

Boris Khusid

Guangliang Gary Liu

Theodore Davidson

David Todd

Bainian Qian

Zhixing Lin

Ramani Susarla

Catharina Knieke

Mohammed A Azad

Maxx Capece

Lu Zhang

Jun Yang

Sangah Kim

Guluzar Gorkem Buyukgoz

Linje Zhu

William Schepige

Caroline H Nam

Eylul Cetindag

Yulu Wang

High (greater than 30%) and/or low (less than 10%) loaded multiple API powdered/nanoparticle were tabulated with increased flowability and physical properties. Properties include blend flowability and uniformity, bulk packing density, compactability, tensile strength, and dissolution. Blending is done through solventless dry mechanical coating of at least one minority API component defined as the API component with the least weight per volume surface coated with nano-sized powders in lesser amounts by wt % of the blend, and preferably less than 10% dry coated of the minority API. An excipient may be dry coated in the lesser amount wherein the excipient is a minority component. Both minority excipient and minority API may be dry coated. Using dry coating instead of dry granulation and/or wet granulation techniques in producing tablets saves manufacturing steps, costs, and produces higher quality tablets with surprisingly higher properties than expected for low flowability solid powdered ingredients.

Powder blend processability improvements through minimal amounts of synergistically selected surface coating agents

The present disclosure provides improved film based pharmaceutical products containing uniformly distributed drug or active agent particles (e.g., to achieve improved/excellent dissolution control including enhancing dissolution and bioavailability and/or product uniformity). More particularly, the present disclosure provides improved systems/methods for fabricating film based pharmaceutical products by utilizing higher surface modified micronized drug or active agent powders and film forming precursors and drying methods that accomplish improved/efficient drying and provide improved/excellent content uniformity of active pharmaceutical agents in the fabricated film based pharmaceutical products. In exemplary embodiments, the present disclosure provides for an easier means of directly incorporating dry micronized poorly water-soluble drugs or active agent particles (e.g., fenofibrate ('FNB')) into films. The present disclosure demonstrates some advantages of direct incorporation of surface modified-micronized poorly water-soluble drug or active agent powders in film manufacturing.

Compositions and methods for preparing polymeric films loaded with uniformly distributed drug particles

The present disclosure provides improved stripfilm based pharmaceutical products (e.g., for enhancing dissolution and bioavailability). More particularly, the present disclosure provides improved systems/methods for fabricating stripfilm based pharmaceutical products by utilizing higher viscosity film forming precursors and drying methods that accomplish improved/faster drying and provide improved/excellent content uniformity of active pharmaceutical agents in the stripfilm based pharmaceutical products. Exemplary systems/methods advantageously use high viscosity, bio-compatible polymeric precursors, (optional use of surface modified drug powders), and convective drying for fabrication of thin films loaded with nano and/or micro sized particles of poorly water-soluble active pharmaceutical ingredients (APIs) to achieve improved active content uniformity and very fast dissolution from poorly water soluble actives, while accomplishing fast drying during the fabrication process. The present disclosure provides for the fast drying (e.g., via low temperature forced convection) of biocompatible polymer films loaded with poorly water-soluble drug nano-particles.

System and method for fabrication of uniform polymer films containing nano and micro particles via continuous drying process

The present disclosure provides improved systems and methods utilizing colloidal/ultrafine superdisintegrant-based composite particles for dispersion and/or dissolution of active pharmaceutical agents. In general, the present disclosure utilizes a surfactant-free or near surfactant-free formulation by incorporating a wet milled SDI as a dispersant in the formulation. As such, the present disclosure provides for the preparation of surfactant-free or substantially surfactant-free formulations (e.g., nano-composite micro-particle formulations) by incorporating a wet-milled superdisintegrant (SDI) as the dispersant in the formulations. The advantageous SDI particles (e.g., colloidal/ultrafine SDI particles) of the present disclosure can be used to break-up the aggregates (e.g., nanoparticle aggregates) of the active agents (e.g. poorly water-soluble drugs) in the formulations (e.g., micro-particle formulations) and enhance the recovery of the nanoparticles of active agents during aqueous re-dispersion and their dissolution rate in vitro and in vivo.

Methods for superdisintegrant-based composite particles for dispersion and dissolution of active pharmaceutical agents

A composite particle including a core with at least one carrier material; a fluidizing material layer on the surface of the core; and an outer layer comprising nanoparticles of an ingestible material distributed in at least one matrix-forming material. A process of making the composite particles includes the steps of dry coating carrier particles with a fluidizing material; preparing a suspension of nanoparticles of an ingestible material distributed in a matrix-forming material; and fluid bed coating the carrier particles with the suspension. The process and products provide quick dissolving composite particles which can be used for delivery of poorly water soluble ingestible materials in suitable dosage forms. The process of the invention reduces or prevents particle agglomeration during fabrication of the composite particles to enable delivery and quick redispersion of nanoparticles of the ingestible material from a dosage form.

Pharmaceutical core-shell composite powder and processes for making the same

Systems and methods for superdisintegrant-based composite particles for dispersion and dissolution of agents

The present invention is a solventless method of producing polymer coated active pharmaceutical ingredient that is taste-masked and may be released in relatively short time. It employs high energy vibrations or acoustic mixing of API particles, water soluble coating material particles and hydrophobic polymer particles, with or without use of other pharmaceutically relevant powders as media. Additionally the method is capable of producing individually coated drug particles without agglomeration or the long drying times associated with solvent based coating methods.

Solventless mixing process for coating pharmaceutical ingredients

A taste masked particulate pharmaceutical formulation include a core that comprises an active pharmaceutical ingredient; at least a partial nanoparticle material layer on the core that comprises a nanoparticle material with a median particle size not greater than 100 nm; a first polymer layer that is at least partially water soluble and a second polymer layer that is water insoluble. The active pharmaceutical ingredient is completely released in 30 minutes in the USP Dissolution Test. A process of making the particulate pharmaceutical formulation using sequential fluidized bed coating steps under controlled conditions is also described.

Taste masked active pharmaceutical powder compositions and processes for making them

A method for the continuous production of finely ground particulates coated with a barrier, or other desirable film wherein the coated particulates exhibit a diameter of less than 10 microns. In an exemplary embodiment, large coated particulates are introduced into a fluid energy, or jet mill, along with smaller, uncoated particulates. As the particulates collide within the mill they are comminuted, and an amount of coating is transferred from the coated particulates to the uncoated ones such that they become sufficiently coated and size-reduced to a desired size. Alternatively, uncoated particulates are milled and coated during their milling. Still alternatively, uncoated particulates are milled and subsequently directed through an atomized mist of coating material wherein the size of the mist droplets are as large, or larger than the directed particulates.

Continuous high-speed coating of finely ground particulates

Techniques and processes that combine particulate coating processes with particulate handling steps resulting in the formation of free-flowing particulates for introduction into energetic product vessels to affect an in-situ, net-shape manufactured product. The processes involve selecting suitably sized materials, processing such materials such that they are surface-coated and/or locally 'structured' particulates, and pouring, preferably 'dry' pouring, these processed materials into an energetic product vessel and infusing the filled vessel with a polymerizable and surface-compatible monomer or oligomer which flows into the unoccupied volume, followed by polymerization of the monomer, which then becomes the binder giving mechanical integrity to the final, net-shape energetic composition.

Netshape manufacturing processes and compositions

With the coupling of an external field and aeration (or a flow of another gas), nanoparticles can be smoothly and vigorously fluidized. A magnetic force and/or pre-treatment may be employed with the fluidizing gas and, when coupled with a fluidizing medium, provide excellent means for achieving homogenous nanofluidization. The magnetic force interacts with non-fluidizing magnetic particles and helps to break channels as well as provide enough energy to disrupt the strong interparticle forces, thereby establishing an advantageous agglomerate size distribution. Enhanced fluidization is reflected by improved performance-related attributes. The fluidized nanoparticles may be coated, surface-treated and/or surface-modified in the fluidized state. In addition, the fluidized nanoparticles may participate in a reaction, either as a reactant or a catalyst, while in the fluidized state.

System and method for nanoparticle and nanoagglomerate fluidization

Systems and methods for achieving filtration are provided that utilize agglomerates or granules of nanoparticles. The agglomerates or granules of nanoparticles may be used as and/or incorporated into a HEPA filtration system to remove solid or liquid submicron-sized particles, e.g., MPPS, in an efficient and efficacious manner. The filtration systems and methods are provided that utilize agglomerates or granules in a size range of about 100-500 microns. The agglomerates or granules of nanoparticles exhibit a hierarchical fractal structure. In the case of agglomerates of nanoparticles, porosities of 0.9 or greater are generally employed, and for granules of nanoparticles, porosities that are smaller than 0.9 may be employed. Filter media formed from the agglomerates or granules may be formed from materials such as carbon black and fumed silica, and may be employed in baffled or non-baffled filtration apparatus.

Fractal structured nanoagglomerates as filter media

A process, method and/or system for preparing polymer-coated nanoparticles and/or other ultrafine particles utilizing a supercritical fluid, e.g., supercritical carbon dioxide (SC CO), as an antisolvent that may be added to a solution of a polymer and an organic solvent in which insoluble nanoparticles or the like are suspended. The coating process occurs when the supercritical fluid (e.g., SC CO) and the nanoparticle-containing suspension are combined to cause the suspended nanoparticles to precipitate as coated nanoparticles. Processing parameters for optimizing and/or enhancing the efficacy and/or efficiency of the coating process, method and/or system and for controlling the coating and/or agglomeration of coated particles are also described. The process, method and/or system has wide ranging applicability, e.g., for coating and/or encapsulation of pharmaceuticals, cosmetics, food products, chemicals, agrochemicals, pesticides, polymers, coatings, catalysts and the like.

Polymer coating/encapsulation of nanoparticles using a supercritical antisolvent process

A process and apparatus for promoting controlled flow of solid material generally comprises a container for holding the solid material and a number of magnetically hard permanent magnet particles within the solid material near the container outlet. The particles are excited with sufficient oscillating electromagnetic energy to create motion and cause sufficient disturbance to break the structure of the solid material and push it out of the outlet.

Method and apparatus for magnetically mediated controlled powder discharge

Coater for coating particles is provided with a casing and a cylinder having apertures rotatably mounted within the casing. Gas is blown into the casing and onto the host particles through the slots of the cylinder. Guest particles may be inserted into the casing initially or subsequently after rotation of the cylinder begins. The particles are fluidized when a balance is attained between the centrifugal force from the rotation of the cylinder and the force exerted upon the particles from the air flow. The centrifugal force exerted on the particles within the cylinder in an operating state is at least about 25 gs so as to cause guest particles of different sizes to be coated onto the host.

Growing community of inventors

Princeton, NJ, United States of America

Rajesh N Dave