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

• Published in: International journal of pharmaceutics 2001-03, Vol.215 (1), p.137-145
• Main Authors: Suihko, Eero, Korhonen, Ossi, Järvinen, Tomi, Ketolainen, Jarkko, Jarho, Pekka, Laine, Ensio, Paronen, Petteri
• Format: Article
• Language: English
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Biological and medical sciences; Chemical Phenomena; Chemistry, Physical; Chromatography, High Pressure Liquid; Cyclodextrins - chemistry; Drug Compounding; Excipients; Freeze Drying; General and cellular metabolism. Vitamins; General pharmacology; Hydroxypropyl-β-cyclodextrin; Medical sciences; Moisture sorption–desorption; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spray-drying; Tableting; Tablets; Tolbutamide; Tolbutamide - administration & dosage; Tolbutamide - chemistry; X-Ray Diffraction
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(00)00682-7

The physicochemical and tableting properties of hydroxypropyl-β-cyclodextrin (HP-β-CD) and its tolbutamide (TBM) complex were studied. The kinetics of TBM/HP-β-CD inclusion complex formation in solution were determined by the phase solubility method. Solid complexes were prepared by freeze-drying and spray-drying. Water sorption–desorption behaviour of the materials were studied and compacts were made using a compaction simulator. TBM and HP-β-CD formed 1:1 inclusion complexes in aqueous solution with an apparent stability constant of 63 M −1. HP-β-CDs and TBM/HP-β-CD complexes were amorphous whereas the freeze-dried and spray-dried TBMs were polymorphic forms II and I, respectively. Sorption–desorption studies showed that HP-β-CDs were deliquescent at high relative humidities. TBM/HP-β-CD complexes had slightly lower water contents at low relative humidities than the physical mixtures. However, at high humidities their water sorption and desorption behaviours were similar to those of corresponding physical mixtures, indicating a glass transition of the complexed materials. TBM/HP-β-CD complexes demonstrated a worse compactibility than similarly prepared HP-β-CDs or physical mixtures. Also particle properties that resulted from these preparation methods affected the compactibility of the materials. In conclusion, the physicochemical and tableting properties of HP-β-CD were modified by complexation it with TBM.