Formulation and characterization of a liquid crystalline hexagonal mesophase region of phosphatidylcholine, sorbitan monooleate, and tocopherol acetate for sustained delivery of leuprolide acetate

• Published in: International journal of pharmaceutics 2016-11, Vol.514 (1), p.314-321
• Main Authors: Báez-Santos, Yahira M., Otte, Andrew, Mun, Ellina A., Soh, Bong-Kwan, Song, Chang-Geun, Lee, Young-nam, Park, Kinam
• Format: Article
• Language: English
• Subjects: alpha-Tocopherol - chemistry; Chemistry, Pharmaceutical - methods; Delayed-Action Preparations - chemistry; Drug delivery; Drug Delivery Systems - methods; Drug Liberation; Erosion; Hexoses - chemistry; Leuprolide - chemistry; Liquid crystal hexagonal mesophase; Liquid Crystals - chemistry; Phosphatidylcholines - chemistry; PLM; SAXS; Scattering, Small Angle; Sustained-release; Water - chemistry; Water uptake; X-Ray Diffraction - methods
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.06.138

[Display omitted] Although liquid crystal (LC) systems have been studied before, their utility in drug delivery applications has not been explored in depth. This study examined the development of a 1-month sustained release formulation of leuprolide acetate using an in situ-forming LC matrix. The phase progression upon water absorption was tested through construction of ternary phase diagrams of phosphatidylcholine, sorbitan monooleate, and tocopherol acetate (TA) at increasing water content. Small angle X-ray scattering revealed the presence of lamellar and hexagonal mesophases. The physicochemical characteristics and in vitro drug release were evaluated as a function of the ternary component ratio and its resultant phase behavior. Formulations with increased water uptake capacity displayed greater drug release and enhanced erodability. Removal of TA resulted in increased water uptake capacity and drug release, where 8% (w/w) TA was determined as the critical concentration threshold for divergence of release profiles. In conclusion, characterization of the resultant HII mesophase region provided information of the impact the individual components have on the physicochemical properties and potential drug release mechanisms. This high mitigating impact of TA on drug release indicates the use of TA as a tailoring agent, broadening the therapeutic applications of this LC system.