1. Field of the Invention
The present invention relates to solutions containing acidic, basic and/or amphoteric pharmaceutical agents for encapsulation in gelatin capsules.
2. Description of the Art
Soft gelatin capsules and hard shell gelatin capsules are well known for the oral administration of pharmaceutical agents. For pharmaceutical agents of relatively low solubility and/or relatively high dosage amount, gelatin capsules can pose problems for the pharmaceutical formulator. For example, if a given pharmaceutical agent has a relatively low solubility, it may need a relatively large volume of solution in order to deliver a unit dose. While it is may be possible to encapsulate such a large volume of solution in a soft gelatin capsule, for example, the resulting capsule may be too large for conventional oral administration to human patients.
In similar fashion, if a pharmaceutical agent requires a relatively high dose, a large volume of solution may be necessary in order to deliver this dose. Encapsulation of this large volume may result in a capsule that is too large for convenient oral administration to human patients.
As one approach to solving this problem in the capsule formulation art, U.S. Pat. No. 5,071,643 (Yu, et al.) discloses the use of polyethylene glycol based solutions for acidic, basic and amphoteric pharmaceutical agents. These polyethylene glycol based solutions contain either an hydroxide species or a hydrogen ion species that causes the appropriate pharmaceutical agent to partially ionize, i.e., the pharmaceutical agent is present in both the free form and the salt form. The partial ionization described in Yu, et al. results in enhanced solubility for the acidic, basic or amphoteric pharmaceutical agent. This enhanced solubility, in turn, may permit the preparation of a solution of pharmaceutical agent that is highly concentrated enough to be encapsulated in a conveniently sized gelatin capsule for oral administration. The Yu, et al. patent discloses that enhanced solubility solutions can be prepared using polyethylene glycol and contemplated equivalents of polyethylene glycol, such as polyethylene glycol ethers of various alcohols and copolymers of polyethylene glycol.
The present inventors have discovered that other solvents may be used to form pharmaceutically acceptable solutions that exhibit enhanced solubility characteristics. These enhanced solubility pharmaceutical solutions have the advantages contemplated by Yu, et al., i.e., encapsulation of dosages in small capsules.