Complexation with tolbutamide modifies the physicochemical and tableting properties of hydroxypropyl-beta-cyclodextrin

The physicochemical and tableting properties of hydroxypropyl-beta -cyclode xtrin (HP-beta -CD) and its tolbutamide (TBM) complex were studied. The kin etics of TBM/HP-beta -CD inclusion complex formation in solution were deter mined by the phase solubility method. Solid complexes were prepared by free ze-drying and spray-drying. Water sorption-desorption behaviour of the mate rials were studied and compacts were made using a compaction simulator. TBM and HP-beta -CD formed 1:1 inclusion complexes in aqueous solution with an apparent stability constant of 63 M-1. HP-beta -CDs and TBM/HP-beta -CD co mplexes were amorphous whereas the freeze-dried and spray-dried TBMs were p olymorphic forms II and I, respectively. Sorption-desorption studies showed that HP-beta -CDs were deliquescent at high relative humidities. TBM/HP-be ta -CD complexes had slightly lower water contents at low relative humiditi es than the physical mixtures. However, at high humidities their water sorp tion and desorption behaviours were similar to those of corresponding physi cal mixtures, indicating a glass transition of the complexed materials. TBM /HP-beta -CD complexes demonstrated a worse compactibility than similarly p repared HP-beta -CDs or physical mixtures. Also particle properties that re sulted from these preparation methods affected the compactibility of the ma terials. In conclusion, the physicochemical and tableting properties of HP- beta -CD were modified by complexation it with TBM. (C) 2001 Elsevier Scien ce B.V. All rights reserved.