[Design Features in the Molecular-level Development of Solid Pharmaceutical Formulations Based on Supramolecular Structures].

[Design Features in the Molecular-level Development of Solid Pharmaceutical Formulations Based on Supramolecular Structures]. Yakugaku Zasshi. 2019;139(2):157-164 Authors: Higashi K, Ueda K, Moribe K Abstract We focused on the crystal structure of cyclodextrin (CD) to develop new solid CD complexes. There are two large spaces in the columnar structure of CD crystals: one inside a CD cavity and another between CD columns. New solid CD complexes can be designed by incorporating guest drugs between the CD columns. We succeeded in preparing a solid drug/[polyethylene glycol (PEG)/γ-CD-polypseudoraxane (PPRX)] complex by a sealed-heating method via the gas phase. A drug/(PEG/γ-CD-PPRX) complex has a structure in which PEGs are included in a γ-CD cavity, and guest drugs are incorporated between the γ-CD columns. Screening by a sealed-heating method determined that a variety of guest drugs with varying molecular size and log P could be incorporated into the spaces between γ-CD columns, following a stoichiometric rule. Another method, via solid phase using cogrinding and subsequent heating, was developed to prepare drug/(PEG/γ-CD-PPRX) complex. This method enabled us to prepare the complex with a thermally unstable drug, as well as a drug/(PEG/α-CD-PPRX) complex not formed using the sealed-heating method. Both the structure and molecular state of each drug in the complexes were characterized by powder X-ray diffraction and solid-state...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research