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. 2022 Mar 25:2022:1662194.
doi: 10.1155/2022/1662194. eCollection 2022.

Design and Characterization of Agarose/HPMC Buccal Films Bearing Ondansetron HCl In Vitro and In Vivo: Enhancement Using Iontophoretic and Chemical Approaches

Umair Jillani  1 , Jahanzeb Mudassir  1 , Qazi Amir Ijaz  2   3 , Sumera Latif  4 , Nadia Qamar  3 , Ambreen Aleem  1 , Ejaz Ali  3 , Khizar Abbas  1 , Muhammad Asif Wazir  1 , Amjad Hussain  3 , Nasir Abbas  3 , Muhammad Sohail Arshad  1
Affiliations

Design and Characterization of Agarose/HPMC Buccal Films Bearing Ondansetron HCl In Vitro and In Vivo: Enhancement Using Iontophoretic and Chemical Approaches

Umair Jillani et al. Biomed Res Int. .

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Abstract

The study was aimed at designing and characterizing the ondansetron hydrochloride (OND) bearing agarose (AG), and hydroxypropyl methyl cellulose (HPMC) mucoadhesive buccal films employing glycerol as a plasticizer. The buccal delivery of ondansetron hydrochloride was remarkably boosted by employing physical (iontophoresis) and chemical enhancement approaches (chemical penetration enhancers). To explore the influence of different formulation components, i.e., agarose, hydroxypropyl methyl cellulose (HPMC), and glycerol on various evaluating parameters, i.e., tensile strength, swelling index, ex vivo mucoadhesion time, and subsequently on in vitro drug release, a D-optimal design was opted. A buccal film bearing OND was mounted on bovine buccal mucosa for ex vivo permeation studies and impact of chemical and physical enhancement techniques on the permeation profile was also analysed. A linear release profile was revealed in in vitro drug release of OND over 60 minutes and outcomes ascertained the direct relationship between HPMC content and in vitro drug release and inverse relationship was depicted by AG content. The FTIR and DSC thermal analysis was executed to determine the physicochemical interactions and results exposed no chemical interactions between drug and polymers. The drug (OND) appeared as tiny crystals on smooth film surface during scanning electron microscopy (SEM) analysis. A notable enhancement in permeation flux, i.e., 761.02 μg/min of OND during ex vivo permeation studies was witnessed after the application of current (0.5-1 mA) without any time lag and with enhancement ratio of 3.107. A time lag of 15 minutes, 19 minutes, and 26 minutes with permeation flux of 475.34 μg/min, 399.35 μg/min, and 244.81 μg/min was observed after chemical enhancer pretreatment with propylene glycol, Tween 80, and passive, respectively. Rabbit was employed as the experimental animal for pharmacokinetic studies (in vivo) and cats for pharmacological activity (in vivo), and the results illustrated the enhanced bioavailablity (2.88 times) in the iontophoresis animal group when compared with the rabbits of control group. Likewise, a remarkable reduction in emesis events was recorded in cats of iontophoresis group. Conclusively, the histopathological examinations on excised buccal mucosa unveiled no severe necrotic or cytopathetic outcomes of current.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Response surface plots, tensile strength (a, b, c), swelling index (d, e, and f), and ex vivo mucoadhesion time (g, h, and i).
Figure 2
Figure 2
Effect of different polymeric concentrations, i.e., agarose (a), HPMC (b), and plasticizer (c) on % drug release.
Figure 3
Figure 3
DSC thermograms of pure polymers, drug, and buccal films.
Figure 4
Figure 4
(a) FTIR spectra of pure polymers and drug, (b) FTIR spectra of buccal films.
Figure 5
Figure 5
X-ray diffractograms of pure polymers, drug and buccal films.
Figure 6
Figure 6
Buccal film images (F8 and F8DL). Scanning electron micrograph of mucoadhesive buccal films (a and b), SEM micrograph of buccal film (F8) (c and d), and SEM micrograph of ondansetron-loaded buccal film (F8DL) (e and f).
Figure 7
Figure 7
The cummulative release (%) verses time (t). Effect of chemical enhancers, iontophoresis, and combined effect of both chemical enhancers and iontophoresis on the ondansetron (OND) permeation through the buccal mucosa.
Figure 8
Figure 8
The enhancement ratios of passive treatment-I, chemical enhancers treatment-II, iontophoresis treatment-III and combined treatment of both chemical enhancer and iontophoresis treatment-IV on permeation of ondansetron (OND) across the buccal mucosa.
Figure 9
Figure 9
Histological sections of the buccal mucosa, (a) histological section of control, (b) histological section after passive permeation treatment-I, (c) histological section after pretreatment with Tween 80, (d) histological section after pretreatment with propylene glycol treatment-II, (e) histological section after application of current treatment-III, and (f) histological section after combined treatment with chemical enhancer and current treatment-IV.
Figure 10
Figure 10
(a) The chromatograms of ondansetron hydrochloride. (b) The plasma concentration versus time curve of both the passive and ionto animal groups.
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