Abstract: Embodiments of the present technology may include a system for forming an emulsion. The system may include a coiled tube. The coiled tube may have a first end and a second end. The second end may be located at a position higher than the position of the first end. The system may also include a plurality of beads disposed within the coiled tube. The system may further include a first inlet fluidly connected to the coiled tube. The first inlet may be configured to deliver a first fluid to the first end before the second end. In addition, the system may include a second inlet fluidly connected to the coiled tube. The second inlet may be configured to deliver a second fluid to the first end before the second end.

Abstract: The invention is directed to a single-step method for rapidly and efficiently preparing protein-polymer conjugates, including an insulin-polymer conjugate. According to the method of the present invention, a protein and hydrophilic polymer are contacted in the presence of at least one organic solvent and at least one metal chelator, under conditions that promote the formation of a conjugate of the protein and polymer. Thus, the invention is directed to the site-specific modification of selected proteins, such as insulin, with poly(ethylene glycol) at residue PheB1. The invention also provides a pharmaceutical formulation for encapsulating the conjugate in a biodegradable polymer.

Abstract: Embodiments may also include a system for reducing a solvent concentration in a plurality of microparticles. The system may include a solvent extraction tank. In the solvent extraction tank, a mixture including the plurality of microparticles and the solvent may be contacted with water to form an aqueous suspension. A first portion of the solvent may dissolve into the water of the aqueous suspension to reduce the solvent concentration in the plurality of microparticles. The system may also include a concentration unit in fluid communication with the solvent extraction tank. The concentration unit may further reduce the solvent concentration in the plurality of microparticles. A microparticle concentrate may be formed. The system may further include a washing unit. In the washing unit, the microparticle concentrate may be contacted with a washing solution and may form an amalgam of washed particles.

Abstract: Embodiments may include a method for reducing a solvent concentration in a plurality of microparticles. The method may involve contacting a mixture including the plurality of microparticles and the solvent with water to form an aqueous suspension. A first portion of the solvent may dissolve into the water of the aqueous suspension to reduce the solvent concentration in the plurality of microparticles from a first solvent concentration in the mixture to a second solvent concentration in the aqueous suspension. The method may also include transferring the aqueous suspension to a concentration unit that may further reduce the solvent concentration from the second solvent concentration to a third solvent concentration. The method may further include transferring a microparticle concentrate with the third solvent concentration to a washing unit to form an amalgam of washed microparticles with a fourth solvent concentration. The method may also include drying the amalgam of washed microparticles.

Abstract: Examples include a method of making a protein-PEG conjugate. The method may include providing an aqueous protein solution. The aqueous protein solution may include a protein, a pH buffer, and a chelating agent. The chelating agent may be chosen from the group consisting of an aminopolycarboxylic acid, a hydroxyaminocarboxylic acid, an N-substituted glycine, 2-(2-amino-2-oxocthyl) aminoethane sulfonic acid (BES), and deferoxamine (DEF). The method may also include introducing sodium cyanoborohydride and a methoxy polyethylene glycol aldehyde to the aqueous protein solution. The sodium cyanoborohydride in the methoxy polyethylene glycol aldehyde may have a molar ratio ranging from about 5:1 to about 1.5:1. The method may further include reacting the methoxy polyethylene glycol aldehyde with the protein to form the protein-PEG conjugate. The pH buffer may maintain a pH of the aqueous protein solution ranging from 4.0 to 4.4 during the reaction.

Abstract: Embodiments may include a method for reducing a solvent concentration in a plurality of microparticles. The method may involve contacting a mixture including the plurality of microparticles and the solvent with water to form an aqueous suspension. A first portion of the solvent may dissolve into the water of the aqueous suspension to reduce the solvent concentration in the plurality of microparticles from a first solvent concentration in the mixture to a second solvent concentration in the aqueous suspension. The method may also include transferring the aqueous suspension to a concentration unit that may further reduce the solvent concentration from the second solvent concentration to a third solvent concentration. The method may further include transferring a microparticle concentrate with the third solvent concentration to a washing unit to form an amalgam of washed microparticles with a fourth solvent concentration. The method may also include drying the amalgam of washed microparticles.

Abstract: Embodiments may include a method for reducing a solvent concentration in a plurality of microparticles. The method may involve contacting a mixture including the plurality of microparticles and the solvent with water to form an aqueous suspension. A first portion of the solvent may dissolve into the water of the aqueous suspension to reduce the solvent concentration in the plurality of microparticles from a first solvent concentration in the mixture to a second solvent concentration in the aqueous suspension. The method may also include transferring the aqueous suspension to a concentration unit that may further reduce the solvent concentration from the second solvent concentration to a third solvent concentration. The method may further include transferring a microparticle concentrate with the third solvent concentration to a washing unit to form an amalgam of washed microparticles with a fourth solvent concentration. The method may also include drying the amalgam of washed microparticles.

Abstract: The invention is directed to a single-step method for rapidly and efficiently preparing protein-polymer conjugates, including an insulin-polymer conjugate. According to the method of the present invention, a protein and hydrophilic polymer are contacted in the presence of at least one organic solvent and at least one metal chelator, under conditions that promote the formation of a conjugate of the protein and polymer. Thus, the invention is directed to the site-specific modification of selected proteins, such as insulin, with poly(ethylene glycol) at residue PheB1. The invention also provides a pharmaceutical formulation for encapsulating the conjugate in a biodegradable polymer.