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

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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 < 0.05) higher AUC0–24 and AUC 0–∞values. Non-significant differences between Cmax and tmax values were revealed.

Conclusion

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

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Authors and Affiliations

  1. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo, Egypt

    Hussein Osman Ammar & Aya Adel Fouly

  2. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt

    Magdy Ibrahim Mohamed & Mina Ibrahim Tadros

  3. Department of Pharmaceutics, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Egypt

    Aya Adel Fouly

Authors
  1. Hussein Osman Ammar
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  2. Magdy Ibrahim Mohamed
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  3. Mina Ibrahim Tadros
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  4. Aya Adel Fouly
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Correspondence to Mina Ibrahim Tadros.

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Research involving human and animal rights

The animal studies were performed after receiving approval of the research ethics committee for experimental and clinical studies at the Faculty of Pharmacy, Future University in Egypt (Approval Number: REC-FPSPI-2/15).

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Ammar, H.O., Mohamed, M.I., Tadros, M.I. et al. High frequency ultrasound mediated transdermal delivery of ondansetron hydrochloride employing bilosomal gel systems: ex-vivo and in-vivo characterization studies. J. Pharm. Investig. 50, 613–624 (2020). https://doi.org/10.1007/s40005-020-00491-y

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