pH Modulation as a Key Strategy for Developing a Stable Lyotropic Liquid Crystal Formulation of Octreotide Acetate
Yingshun Xin, Shupei Yang, Chan Li, Yaya Chang, Meiling Luo, Ying Yan, Jia Liu, Yulin Liu, Yajuan Wang, Chunlei Li
TL;DR
This paper shows how adjusting pH can stabilize octreotide acetate in a liquid crystal formulation for long-term drug delivery.
Contribution
The study introduces pH modulation as a novel strategy to stabilize octreotide acetate in lyotropic liquid crystal systems.
Findings
Adjusting pH to 5.7 enabled >90% drug stability after 3 months at 40°C and >98% after 12 months at 4°C.
The formulation showed sustained release in vivo with prolonged systemic exposure and extended half-life.
The LLC system's pharmacokinetic profile matched that of octreotide hydrochloride LLC.
Abstract
Background: Lyotropic liquid crystal (LLC) systems provide sustained release and convenient administration for peptide delivery. Octreotide, a first-line somatostatin analogue, has previously been formulated into LLC systems mainly using the hydrochloride salt. Here, we investigated the acetate salt, which is widely used in marketed products, but presents unique challenges in LLC formulation due to poor stability. Methods: We demonstrate that pH adjustment is a critical determinant for successfully incorporating octreotide acetate into a stable LLC system. By employing 3M HCl–EtOH to adjust pH to approximately 5.7, we obtained a formulation that maintained >90% drug content after 3 months at 40 °C and >98% after 12 months at 4 °C. Results: Structural analyses confirmed the coexistence of cubic and hexagonal mesophases, supporting controlled release. In vivo pharmacokinetic studies in…
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Taxonomy
TopicsLipid Membrane Structure and Behavior · Liquid Crystal Research Advancements · Advanced Drug Delivery Systems