Methods for the formulation of biodegradable microparticles for delivery of protein drugs, such as botulinum toxin, have been developed. The methods include the steps of precipitating and washing proteins with organic solvent to remove water prior to dispersing in polymer-dissolved organic solvent to prevent exposure to water/solvent interfaces and maintain bioactivity of the protein drugs and fabrication of microparticles by either template or emulsion method. Biodegradable microparticles, formed of one or more biodegradable polymers having entrapped in the polymer one or more protein agents, such as botulinum toxin, are also provided. Precipitated botulinum toxin and botulinum toxin-loaded microparticles can also be formulated into thermogels or crosslinked hydrogels. The stability of the protein within these microparticles, as well as the controlled release of the entrapped agents, provides for sustained efficacy of the agents.

Methods for the formulation of biodegradable microparticles for delivery of protein drugs, such as botulinum toxin, have been developed. The methods include the steps of precipitating and washing proteins with organic solvent to remove water prior to dispersing in polymer-dissolved organic solvent to prevent exposure to water/solvent interfaces and maintain bioactivity of the protein drugs and fabrication of microparticles by either template or emulsion method. Biodegradable microparticles, formed of one or more biodegradable polymers having entrapped in the polymer one or more protein agents, such as botulinum toxin, are also provided. Precipitated botulinum toxin and botulinum toxin-loaded microparticles can also be formulated into thermogels or crosslinked hydrogels. The stability of the protein within these microparticles, as well as the controlled release of the entrapped agents, provides for sustained efficacy of the agents.

A method for producing metal chloride M.sup.x+Clx includes reacting metal carbonate in solid form using phosgene, diphosgene and/or triphosgene to form metal chloride M.sup.x+Clx, wherein the metal M is selected from the group containing alkali metals, alkaline earth metals, Al and Zn, Li and Mg, or Li, for example, and x corresponds to the valency of the metal cations. An apparatus for performing such method is also disclosed.

A method for producing metal chloride M.sup.x+Clx includes reacting metal carbonate in solid form using phosgene, diphosgene and/or triphosgene to form metal chloride M.sup.x+Clx, wherein the metal M is selected from the group containing alkali metals, alkaline earth metals, Al and Zn, Li and Mg, or Li, for example, and x corresponds to the valency of the metal cations. An apparatus for performing such method is also disclosed.