Pharmaceutical formulation with improved solubility and bioavailability
The present invention relates to a pharmaceutical formulation comprising at least one active pharmaceutical ingredient (API) having low aqueous solubility or a pharmaceutically acceptable salt thereof in the form of particles of a size between 1 and 800 nm, wherein said particles are encapsulated within a large microparticle of a size between 1 and 100 μm formed by a matrix comprising at least an excipient. Therefore, the API is entrapped or encapsulated in the microparticles of excipients. This pharmaceutical formulation contains the pharmaceutical active ingredient having improved solubility and subsequently supra-bioavailability.
1. A method to prepare sub-micron particles between 1 and 800 nm of at least one active pharmaceutical ingredient or pharmaceutical acceptable salt thereof encapsulated into microparticles between 1 and 100 μm comprising excipients, the method practiced in a facility comprising:
an injection unit, which is an electronebulizer, comprising at least:
one inlet for an emulsion;
one inlet for injection gas; and
one outlet for droplets through which sprayed droplets of emulsion are released, a drying unit, which is arranged after the injection unit, and
a collection unit, arranged after the drying unit;
the method comprises the following steps:
a) preparing of an emulsion comprising:
at least one active pharmaceutical ingredient or pharmaceutically acceptable salt thereof to be encapsulated,
one or more excipients;
at least two non-miscible or partially miscible solvents or two miscible solvents that by solubilizing the API or the excipients become non-miscible or partially miscible solvents,
b) forming droplets of nano-embedded microparticles in only one step by the electronebulizer from the emulsion obtained in stage (a) in the presence of an injection gas flow that creates the droplets and applying a voltage of between 0.1 kV and 500 kV at the outlet of the injection unit,
c) drying the droplets obtained in stage (b) in the drying unit at a controlled room temperature to obtain the microparticles; and
d) collecting the microparticles obtained in stage (c) by means of the collection unit.
2. The method according to claim 1 wherein the excipient used in stage a) further comprising a surfactant to stabilize the emulsion.
3. The method according to claim 1 wherein the solvents used in step a) are selected from the list consisting of: water, alcohol, toluene, ethyl acetate, methylene chloride, chloroform, dimethyl sulfoxide, dimethyl formamide, tetrahydrofuran, deep eutectic solvents, natural deep eutectic solvents and combinations thereof.