title: Formulation and characterization of a liquid crystalline hexagonal mesophase region of phosphatidylcholine, sorbitan monooleate, and tocopherol acetate for sustained delivery of leuprolide acetate.
abstract: 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 HIImesophase 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.
authors.affiliation: Purdue University, Weldon School of Biomedical Engineering, West Lafayette, IN 47907, USA.
authors.forename: Yahira M
authors.initials: YM
authors.lastname: Báez-Santos
authors.affiliation: Purdue University, Weldon School of Biomedical Engineering, West Lafayette, IN 47907, USA. Electronic address: aotte@purdue.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Otte
authors.affiliation: Purdue University, Weldon School of Biomedical Engineering, West Lafayette, IN 47907, USA.
authors.forename: Ellina A
authors.initials: EA
authors.lastname: Mun
authors.affiliation: Chong Kun Dang Research Institute, 315-20, Dongbaekjukjeondaero, Giheung-gu, Youngin-si, Gyeonggi-do, 16995, Republic of Korea.
authors.forename: Bong-Kwan
authors.initials: BK
authors.lastname: Soh
authors.affiliation: Chong Kun Dang Research Institute, 315-20, Dongbaekjukjeondaero, Giheung-gu, Youngin-si, Gyeonggi-do, 16995, Republic of Korea.
authors.forename: Chang-Geun
authors.initials: CG
authors.lastname: Song
authors.affiliation: Chong Kun Dang Research Institute, 315-20, Dongbaekjukjeondaero, Giheung-gu, Youngin-si, Gyeonggi-do, 16995, Republic of Korea.
authors.forename: Young-Nam
authors.initials: YN
authors.lastname: Lee
authors.affiliation: Purdue University, Weldon School of Biomedical Engineering, West Lafayette, IN 47907, USA; Purdue University, Department of Industrial and Physical Pharmacy, West Lafayette, IN 47907, USA.
authors.forename: Kinam
authors.initials: K
authors.lastname: Park
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D006601:Hexoses / Q000737:chemistry*; D016729:Leuprolide / Q000737:chemistry; D050866:Liquid Crystals / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D053838:Scattering, Small Angle; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods; D024502:alpha-Tocopherol / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D006601:Hexoses; D010713:Phosphatidylcholines; D014867:Water; C018665:sorbitan monooleate; D016729:Leuprolide; D024502:alpha-Tocopherol
keywords: Drug delivery; Erosion; Liquid crystal hexagonal mesophase; PLM; SAXS; Sustained-release; Water uptake