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High frequency ultrasound mediated transdermal delivery of ondansetron hydrochloride employing bilosomal gel systems: ex-vivo and in-vivo characterization studies

Journal of Pharmaceutical Investigation 2020년 50권 6호 p.613 ~ 624
Ammar Hussein Osman, Mohamed Magdy Ibrahim, Tadros Mina Ibrahim, Fouly Aya Adel,
소속 상세정보
 ( Ammar Hussein Osman ) - Future University in Egypt Faculty of Pharmaceutical Sciences and Pharmaceutical Industries Department of Pharmaceutics and Pharmaceutical Technology
 ( Mohamed Magdy Ibrahim ) - Cairo University Faculty of Pharmacy Department of Pharmaceutics and Industrial Pharmacy
 ( Tadros Mina Ibrahim ) - Cairo University Faculty of Pharmacy Department of Pharmaceutics and Industrial Pharmacy
 ( Fouly Aya Adel ) - Future University in Egypt Faculty of Pharmaceutical Sciences and Pharmaceutical Industries Department of Pharmaceutics and Pharmaceutical Technology

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?
Conclusion: The best achieved system (BGS10-HFU) can increase OND bioavailability and initiate a rapid onset of action.

키워드

Ondansetron hydrochloride; Sonophoresis; High frequency ultrasound waves; Bilosomal gel systems

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