Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 532, Issue 1, Pages 345-351Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2017.08.098
Keywords
Liquid crystal; SAXS; Subcutaneous drug delivery; Sustained-release; Hexagonal mesophase; Leuprolide
Categories
Funding
- Chong Kun Dang Pharmaceutical Corp.
- U.S. DOE [DE-AC02-06CH11357]
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A liquid crystalline (LC) system, composed of phosphatidylcholine, sorbitan monoleate, and tocopherol acetate, was investigated to understand the in vivo transformation after subcutaneous injection, coupled with the physicochemical and pharmacokinetic properties of the formulation. The rat model was utilized to monitor a pseudo-time course transformation from a precursor LC formulation to the LC matrix, coupled with the blood concentration profiles of the formulations containing leuprolide acetate. Three formulations that result in the H-U phase, demonstrating dissimilar in vitro release profiles, were used. The formulation showing the highest AUC, C-max and T-max, also displayed the greatest release rate in vitro, the lowest viscosity (LC matrix), and an earlier transformation (LC precursor to matrix) in vivo. A potential link between viscosity, phase transformation, and drug release properties of a liquid crystalline system is described.
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