Floating lipid beads for the improvement of bioavailability of poorly soluble basic drugs: In-vitro optimization and in-vivo performance in humans

• 24 full factorial designs were adopted to formulate optimized lipid beads.
• Optimized formula showed excellent floating properties.
• Lipid beads are easily tailored by changing its composition to achieve desired release profile.
• Optimized formula improved Cinnarizine bioavailability as example of poorly soluble basic drug.
• Lipid beads are potentially suitable for once daily administration.

The challenge in developing oral drug delivery systems of poorly soluble basic drugs is primarily due to their pH dependent solubility. Cinnarizine (CNZ), a model for a poorly soluble basic drug, has pH dependent solubility; where it dissolves readily at low pH in the stomach and exhibits a very low solubility at pH values greater than 4. It is also characterized by a short half life of 3–6 h, which requires frequent daily administration resulting in poor patient compliance. In an attempt to solve these problems, extended release floating lipid beads were formulated. A 24 full factorial design was utilized for optimization of the effects of various independent variables; lipid:drug ratio, % Pluronic F-127, % Sterotex, and Gelucire 43/01:Gelucire 50/13 ratio, on the loading efficiency and release of CNZ from the lipid beads. In-vivo pharmacokinetic study of the optimized CNZ-lipid beads compared to Stugeron® (reference standard) was performed in healthy human volunteers. A promising approach for enhancing the bioavailability of the poorly soluble basic drug, CNZ, utilizing novel and simple floating lipid beads was successfully developed. Zero order release profile of CNZ was achieved for 12 h. Mean AUC0–24 and AUC0–∞ of the optimized CNZ-loaded lipid beads were 4.23 and 6.04 times that of Stugeron® tablets respectively.

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