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 H 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.

Injectable Lipid-Based Depot Formulations: Where Do We Stand?

“…The siRNA was released in a complex with PEI, which protects the siRNA against degradation, but experimental data about the gene silencing efficiencies of the released siRNA are missing to date. Overall, the groups developing liquid crystalline phases as injectable depots have focused mainly on the characterization of the systems using methods like small angle X-ray scattering, electron or polarized light microscopy, rheology, and in vitro drug release studies [98,124,143]. Besides measuring drug plasma concentrations, little attention has been paid to additional in vivo characterization like the fate of the depot after injection, possible local side effects, and biocompatibility or the pharmacological effect.…”

“…Narrow-sized water channels in the liquid crystal structure cause the sustained release behavior of low-molecular-weight drugs but might inhibit the release of molecules with higher molecular weight and therefore demand the addition of hydration-modulating agents [ 142 ]. The in vitro duration of action of the depot effect ranges from several days for bufalin [ 125 ], to 10 days for minocycline [ 126 ], or up to one month for leuprolide acetate [ 98 ], and can be easily tuned by adjusting the ratios of the used compounds [ 121 ]. A novel non-viral gene delivery system was designed by Borgheti-Cardoso et al, combining liquid crystals with polyethylenimine (PEI) to complex siRNA (small interfering RNA) [ 129 ].…”

“… Overview of semisolid and in situ forming depot systems, for example phospholipid phase separation gels, vesicular phospholipid gels, or liquid crystalline phases. ( a ) Reprinted from [ 95 ]; ( b ) top image reprinted from [ 96 ]; ( b ) Bottom image reprinted from reprinted from [ 97 ]; ( c ) Left image reprinted from [ 98 ] with permission from Elsevier; ( c ) Right image published by The Royal Society of Chemistry [ 99 ]. …”

Efficacy of Phytopharmaceuticals From the Amazonian Plant Libidibia ferrea for Wound Healing in Dogs

“…The topical phytopharmaceutical based on murumuru butter (PyM) exhibits in the PLM birefringence with streak textures, which is a characteristic of the hexagonal phase. Crystalline liquid systems of the hexagonal type can resist erosion by body fluids and increase the retention time of the formulation at the site of application, enabling a sustained release of drugs, and enhancing therapeutic efficacy (23). In the centrifugation test, the polymer chains in the PyC remained intact, without phase separation.…”

The Investigations of Construction and in vitro Release of Curcumin Lyotropic Liquid Crystals: Phase Diagrams, Small Angle X‐ray Scattering, Rheological Technology, and Release Kinetics

“…Lyotropic liquid crystals (LLC) are a self-assembling intermediate formed by the directional alignment of amphiphile surfactants under the induction of solvent (Baez-Santos et al, 2016). They have the characteristics of both liquid and solid crystals, exhibiting long-range ordered and shortrange disordered behaviors (Seddon and Templer, 1995).…”