This review covers recent developments in the area of particle engineering via spray drying. The last decade has seen a shift from empirical formulation efforts to an engineering approach based on a better understanding of particle formation in the spray drying process. Microparticles with nanoscale substructures can now be designed and their functionality has contributed significantly to stability and efficacy of the particulate dosage form. The review provides concepts and a theoretical framework for particle design calculations. It reviews experimental research into parameters that influence particle formation. A classification based on dimensionless numbers is presented that can be used to estimate how excipient properties in combination with process parameters influence the morphology of the engineered particles. A wide range of pharmaceutical application examples—low density particles, composite particles, microencapsulation, and glass stabilization—is discussed, with specific emphasis on the underlying particle formation mechanisms and design concepts.

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Pharmaceutical particle engineering via spray drying.

The present invention is directed to secreted and transmembrane polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Secreted and Transmembrane Polypeptides and Nucleic Acids Encoding the Same

The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems--a review.

Methods are provided for inhibiting stenosis following vascular trauma or disease in a mammalian host, comprising administering to the host a therapeutically effective dosage of a therapeutic conjugate containing a vascular smooth muscle binding protein that associates in a specific manner with a cell surface of the vascular smooth muscle cell, coupled to a therapeutic agent dosage form that inhibits a cellular activity of the muscle cell. Methods are also provided for the direct and/or targeted delivery of therapeutic agents to vascular smooth muscle cells that cause a dilation and fixation of the vascular lumen by inhibiting smooth muscle cell contraction, thereby constituting a biological stent.

Therapeutic inhibitor of vascular smooth muscle cells

Devices formed of or including biocompatible polyhydroxyalkanoates are provided with controlled degradation rates, preferably less than one year under physiological conditions. Preferred devices include sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins (including bone filling augmentation material), adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats. The polyhydroxyalkanoates can contain additives, be formed of mixtures of monomers or include pendant groups or modifications in their backbones, or can be chemically modified, all to alter the degradation rates. The polyhydroxyalkanoate compositions also provide favorable mechanical properties, biocompatibility, and degradation times within desirable time frames under physiological conditions.

Medical devices and applications of polyhydroxyalkanoate polymers

The present invention relates to a composition for the modulated release of a biologically active agent. The composition comprises a biocompatible polymeric matrix, a biologically active agent which is dispersed within the polymeric matrix, and a metal cation component which is separately dispersed within the polymeric matrix, whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix. The present invention also relates to a method for modulating the release of a biologically active agent from a biocompatible polymeric matrix, comprising the steps of dissolving a biocompatible polymer in a solvent to form a polymer solution and also separately dispersing a metal cation component and a biologically active agent within the polymer solution. The polymer solution is then solidified to form a polymeric matrix, wherein at least a significant portion of the metal cation component is dispersed in the polymeric matrix separately from the biologically active protein, and whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix.

Modulated release from biocompatible polymers

The method of the invention for producing a composition for the sustained release of biologically active hGH includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, metal cation-stabilized hGH in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said hGH particles.

Composition for sustained release of human growth hormone

ACTH polymeric controlled release systems are described wherein the ACTH retains good biological activity and is released over an extended period of time following administration by injection. In the preferred embodiment, the ACTH polymeric microspheres are made using very cold temperatures to freeze the polymer-ACTH mixtures into polymeric microspheres with very high retention of biological activity and material. Sustained release of biologically active ACTH is achieved when the microspheres are tested in vitro, extending over a period of greater than one day to several months. Altered release can be achieved by inclusion of degradation modifiers, pore forming agents, and stabilizers of the ACTH.

Controlled release acth containing microspheres

Methods and apparatus are provided for making particles comprising: (a) spraying an emulsion, solution, or suspension, which comprises a solvent and a bulk material (e.g., a pharmaceutical agent), through an atomizer and into a primary drying chamber, having a drying gas flowing therethrough, to form droplets comprising the solvent and bulk material dispersed in the drying gas; (b) evaporating, in the primary drying chamber, at least a portion of the solvent into the drying gas to solidify the droplets and form particles dispersed in drying gas; and (c) flowing the particles and at least a portion of the drying gas through a jet mill to deagglomerate or grind the particles. By coupling spray drying with “in-line” jet milling, a single step process is created from two separate unit operations, and an additional collection step is advantageously eliminated. The one-step, in-line process has further advantages in time and cost of processing.

Methods and apparatus for making particles using spray dryer and in-line jet mill

A composition, and methods of forming and using said composition, for the sustained release of non-aggregated, biologically active, erythropoietin (EPO). The sustained release composition of this invention comprises a polymeric matrix of a biocompatible polymer and particles of biologically active, aggregation-stabilized EPO, wherein said particles are dispersed within the biocompatible polymer. The method of the invention for producing a composition for the sustained release of biologically active EPO, includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, aggregation-stabilized EPO in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said EPO particles. The method for using a composition of the invention is a method for providing a therapeutically effective blood level of biologically active, non-aggregated erythropoietin in a subject for a sustained period. In this method, a subject is administered an effective dose of the sustained release composition of the present invention.

Howard Bernstein

Papers

Modulated release from biocompatible polymers

Composition for sustained release of human growth hormone

Controlled release acth containing microspheres

Methods and apparatus for making particles using spray dryer and in-line jet mill

Composition for sustained release of non-aggregated erythropoietin