High frequency ultrasound mediated transdermal delivery of ondansetron hydrochloride employing bilosomal gel systems: ex
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Online ISSN 2093-6214 Print ISSN 2093-5552
ORIGINAL ARTICLE
High frequency ultrasound mediated transdermal delivery of ondansetron hydrochloride employing bilosomal gel systems: ex‑vivo and in‑vivo characterization studies Hussein Osman Ammar1 · Magdy Ibrahim Mohamed2 · Mina Ibrahim Tadros2 · Aya Adel Fouly1,3 Received: 6 March 2020 / Accepted: 7 May 2020 © The Korean Society of Pharmaceutical Sciences and Technology 2020
Abstract Purpose Ondansetron hydrochloride (OND) suffers from rapid elimination (t1/2 = 3–4 h), moderate bioavailability (60%) and inconvenience following oral administration in emetic patients. As an alternative convenient approach, the current work explored the potential of high-frequency ultrasound (HFU) waves to promote transdermal delivery of OND via bilosomal gel systems (BGS) in an attempt to increase OND bioavailability and achieve a rapid onset of action in patients suffering from emesis. Methods OND-loaded BGS were prepared and characterized for pH and rheologic properties. The variables influencing HFU were optimized, viz. bilosomal system: coupling-gel ratio (1:2 or 1:3), application period (5, 10 or 15 min) and (iii) ultrasound intensity (medium or high), mode (continuous or pulsed) & duty cycle (20, 50 or 100%). Ex-vivo permeation and confocal laser scanning microscopy (CLSM) studies were conducted. The best achieved BGS (BGS10-HFU) was subjected to histopathologic and pharmacokinetic studies in rats. Results OND-loaded BGS were shear thinning systems having tolerable pH values for skin application. The optimized HFU variables involved the utilization of a bilosomal system: coupling-gel ratio of 1:3 and the application of high intensity, continuous and 100% duty cycle ultrasound waves for 10 min. Ex-vivo permeation and CLSM studies revealed the superiority of BGS10 following HFU-pretreatment. BGS10-HFU exhibited minor histopathologic changes. Compared to an oral OND solution, BGS10-HFU system had significantly (P
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