A novel multi-tiered experimental approach unfolding the mechanisms behind cyclodextrin-vitamin inclusion complexes for enhanced vitamin solubility and stability

作者：Braithwaite Miles C; Kumar Pradeep; Choonara Yahya E; du Toit Lisa C; Tomar Lomas K; Tyagi Charu; Pillay Viness^*

来源：International Journal of Pharmaceutics, 2017, 532(1): 90-104.

DOI：10.1016/j.ijpharm.2017.08.109

• Vitamins
• Cyclodextrins
• Inclusion complex
• Solubility
• Cholecalciferol
• Ascorbic acid and alpha-tocopherol
• In silica molecular modeling

This study was conducted to provide a mechanistic account for understanding the synthesis, characterization and solubility phenomena of vitamin complexes with cyclodextrins (CD) for enhanced solubility and stability employing experimental and in silico molecular modeling strategies. New geometric, molecular and energetic analyses were pursued to explicate experimentally derived cholecalciferol complexes. Various CD molecules (alpha-, beta-, gamma-, and hydroxypropyl beta-w) ere complexed with three vitamins: cholecalciferol, ascorbic acid and a-tocopherol. The Inclusion Efficiency (IE%) was computed for each CD-vitamin complex. The highest IE% achieved for a cholecalciferol complex was for 'beta CDD3-8', after utilizing a unique CD: cholecalciferol molar synthesis ratio of 2.5:1, never before reported as successful. 2HP beta CD-cholecalciferol, gamma CD-cholecalciferol and a-tocopherol inclusion complexes (IC's) reached maximal IE% with a CD:vitamin molar ratio of 5:1. The results demonstrate that IE%, thermal stability, concentration, carrier solubility, molecular mechanics and intended release profile are key factors to consider when synthesizing vitamin-CD complexes. Phase-solubility data provided insights into the design of formulations with IC's that may provide analogous oral vitamin release profiles even when hydrophobic and hydrophilic vitamins are co-incorporated. Static lattice atomistic simulations were able to validate experimentally derived cholecalciferol IE phenomena and are invaluable parameters when approaching formulation strategies using CD's for improved solubility and efficacy of vitamins.

• 出版日期2017-10-30