Design and evaluation of agarose based buccal films containing zolmitriptan succinate: Application of physical and chemical enhancement approaches

• Published in: Journal of drug delivery science and technology Vol. 69; p. 103041
• Main Authors: Jillani, Umair, Mudassir, Jahanzeb, Arshad, Muhammad Sohail, Mehta, Prina, Alyassin, Yasmine, Nazari, Kazem, Yousef, Bushra, Patel, Mohammed, Zaman, Aliyah, Sayed, Elshaimaa, Chang, Ming-Wei, Ali, Amna, Ahmad, Zeeshan
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.03.2022
• Subjects: Buccal; Iontophoresis; Quality-by-design; Zolmitriptan; Quality-by-design; Buccal; Iontophoresis; Films; Zolmitriptan
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2021.103041

The study aimed to develop and improve the buccal delivery of zolmitriptan succinate from mucoadhesive buccal films containing agarose, guar gum as polymers and glycerol as plasticizer via physical (iontophoresis) and chemical enhancement approaches (chemical penetration enhancers). A central composite design was employed to investigate the effect of different formulation constituents on various characteristics including swelling index, tensile strength, ex vivo mucoadhesion time and in vitro drug release. The impact of both the chemical and physical enhancement techniques on ex vivo permeation of zolmitriptan succinate through the buccal films was also studied using goat buccal mucosa. The results of the in vitro drug release profile revealed linear release of the active over 60 min. The results also identified that agarose had an inverse impact on the swelling index and consequently on the in vitro drug release while guar gum has a direct impact on these parameters. The physicochemical interactions between the formulation constituents were evaluated by Fourier Transform Infrared spectroscopy and differential scanning calorimetry. These revealed no chemical interactions between drug and other formulation constituents. The buccal film morphology evaluated by the scanning electron microscopy exhibited a smooth surface with tiny crystals of drug on the film surface. The results of the ex vivo permeation of zolmitriptan succinate showed a remarkable increase in the permeation flux (495.95 μg/min) without any time lag following the application of electric impulse (0.5–1 mA) as compared to passive (174.81 μg/min) with a time lag of 30 min and after the pre-treatment with chemical penetration enhancers (tween-80 279.65 μg/min and propylene glycol 323.53 μg/min) with a time lag of 20 min. The in vivo pharmacokinetic studies on rabbits revealed the enhanced bioavailability in ionto group by 2.756 times as compared to passive group and consequently rapid onset of action. Finally, the histopathological studies exhibited no severe cytopathetic or necrotic effect of current on the buccal mucosa. [Display omitted]