Companies:  Elektrofi (developed Hpercon which are protein microparticles. Gentle dehydration results in smooth, spherical microparticles that dissolve into fully functional protein monomers in the subcutaenous space. They take drug substances (typically in liquid form) and convert it through a series of proprietary methodologies into an ensemble of very smooth and spherical microphartciles. Then those particles are dispersed into an oily carrier medium that is eminetly flowable and syringable, even at very high concentraitons. Throughout the process, the protein molecule’s quality, shap and size are preserved and the concentraiton of injectable microparticle suspensions can ex eed 600 mg/mL. Not only are the formualtions capable of eliminating the need for infusions, they are capable of reducing the frequency of injections by as much as half thanks to the concentrated dosages). 

Brown (US 2007/0207210; see als WO 2005/112893) discloses methods of forming microparticles having a particle size of less than 200 microns, typically form 0.1 um to about 200 um which include an active agent such as an antibody. The particles are formed by added dissolving the active agent in an aqeuous solvent containing a “phase-separation enhancing agent (PSEA)” which induces or enhances the kiquid-solid phase seapration of the active agents from the solution when the solution is subjected tot he step of pahse seapration in which the active agent becomes solid or semi-solis. The PSEA reduces the solubility of the active agent when the solution is broght to the phase separation conditions such as lowering of temeprature. Examples of PSEAs are polymers such as PEG. The microparticels may also include one or more exicpients such as carohydrates, surfactants. 

Formation of Microparticles by Dehydration:

The dehydration of biologics is commonly employed to acheive solid-dose formulation and enhanced staiblity druing long-term preservation. (Needham “Microglassificaiton:  a novel technique for protein dehydration” Pharmaceutical Biotechnolgoy, 103:810-820, 2014). 

Bitterfield (US Patent Application No: 18/058306, published as US 2023/0093954) discloses isolation of enzymes (e.g., lysozyme) and other proteins using dehydration compositions such as pentanol. The dehydration method, referred to as “microglassification” produced particels of lysozyme. 

Needham (US 8,512,754) discloses a composition taht incldues glassified, staiblized particles having a low water activity (between aobut 0.1-0.9) which include an active agent such as a protein/antibody. The particles are produced by preparing a first aqueous phase that include an aqueous solution of the material of interest and a second pahse that incldues dispersing the aqueous phase into a non-aqeuous suspending solvent (deconaol, do-decanol, pentanol, etc) for forming the particles. 

Needham *”Microglassification:  a novel technique for protein dehydration” Pharmaceutical Biotechnolgoy, 103:810-820, 2014) dislsoes a process called “micrograssificaiton” that can rapidly and controllable dehydrate protein solutions into solid amorphous micrsophreres at room temepratures. Bovine serum albumin (BSA) microdroplets were suspended in pentanol or decanol using micropipietes. 

Needham and DeAngelo (US 8,013,022) also discloses using a two-phase micro system of glassificaiton; a frist phase is provided where the protein is prepared so as to form a micro droplet which is then disssolved into a second phase solvent (decanol, etc.). The method creates micro glass beads of a protein in a reduced hydration state, but not one that dehydrates the protin to such an extent taht it looses it ability to function upon reconstiution. 

Petrel (US 9,643,996) disclsoes producing microparticles of between 0.5-300 um that contain a high loading of bioactive macromolecuels such as protiens/antibodies. The processes combine atomization with solvent-assested dehydration (n-decanol; ethanol, pentanes, hexanes, ethers etc. ) to obtain solid particles that retain the biological activity of the payload. Initially, the protein solution is formed. The protein solution is then atomized to form liquid droplets such as by using an ultrasonic flow-through transducer. The liquid droplets formed by the atomization are then collected in a mixed dehydration solvent which dehydrates the protein by absorbing the water, resulting in the generation of protein microparticles. This is known as solvent-assisted dehydration. The prtoein microparticles are then separated form the dehydration solvent as for example by centrifugation, filtration, etc.