In recent years, solid dispersions have attracted attention in the field of oral preparations. Generally, solid dispersions can be obtained by suitably selecting one or more components to be added to a poorly soluble medicament, the production method, etc. Solid dispersions are expected to improve the dissolvability of the poorly soluble medicament so as to enhance its bioavailability.
One example of a well-known method for producing solid dispersions is the solvent method. The solvent method is such that, for example, both the polymer material that is used as a base for solid dispersion and the medicament are dissolved in an organic solvent, and then dried to make the poorly soluble medicament amorphous so that it can be dispersed on a polymer carrier. However, the solvent method adversely affects the environment due to the organic solvent used. For this reason, a dry process has attracted attention as a method which does not require an organic solvent.
One typical example of a method for producing a solid dispersion employing the dry method is that heating and melting a poorly soluble medicament and a base for solid dispersion (carrier) so as to make the medicament amorphous (the hot melt extruder method). Another example of a known method is placing a mixture of a poorly soluble medicament and a base for solid dispersion in a mortar for molding, followed by irradiation with ultrasonic waves to make the medicament amorphous (for example, Non-Patent Document 1), etc.
The former method is a direct heating method, wherein the mixture of a poorly soluble medicament and a base for solid dispersion carrier is directly heated. On the other hand, the latter method is an indirect heating method, wherein the energy generated by irradiation with ultrasonic waves triggers movement and friction in the powder. As a result, the mixture stores heat and is accordingly made amorphous.
Still another example of a known method to produce a solid dispersion is a thermal mechanochemical method, wherein a poorly soluble medicament (nilvadipine, nifedipine) and a water-soluble polymer base (hydroxypropylmethyl cellulose, polyvinyl pyrrolidone) are mixed while being heated at a temperature at which neither of them are melted (for example, Patent Document 1).
Examples of conventionally known bases for solid dispersion usable in such dry methods include polyvinyl pyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC), hydroxypropylmethyl cellulose phthalate (HPMCP), polyvinyl alcohol (PVA), etc. However, a base for solid dispersion that is more desirable for use in a dry method has been demanded in view of the temperature during the heat treatment, degree of the improvement in the dissolvability of a poorly soluble medicament, stability and reproducibility of the dissolvability of poorly soluble medicament, etc.    Patent Document 1: Japanese Unexamined Patent Publication No. 1993-262642    Non-patent Document 1: Journal of Pharmaceutical Science and Technology, Vol. 60 (No. 2), 148-159 (2000)
USPTO Backgrounds
USPTO Backgrounds