Fast Dissolving Sublingual Strips: A Novel Approach for the Delivery of Isosorbide Dinitrate

Abstract

Background: Isosorbide dinitrate (ISDN) is used for treating the angina attacks. In addition, oral ISDN is available in immediate and sustained release formulations and the bioavailability of ISDN is about 20-25% when taken orally. Further, the ISDN films are developed for sublingual drug delivery by improving drug bioavailability. The present study aimed to design and evaluate the physicochemical properties of the film formulation for sublingual delivery of ISDN. Methods: In the present study, sublingual films were prepared by the solvent casting technique using the hydroxypropyl methylcellulose (HPMC) polymers (i.e., 100, 150 and 200 mg) with a different drug to polymer ratios (i.e., 1:5, 1:7.5 and 1:10). Then, ISDN was evaluated for the film appearance, drug content, surface pH, mucoadhesion force, differential scanning calorimetry (DSC), in vitro drug release, and ex vivo permeability. Results: Based on the results, F3 formulation (1:10 ISDN to HPMC ratio) showed acceptable thickness (0.93 mm), weight (11.14 mg), surface pH (7.82), moisture absorption capacity (6.08%), elasticity (>200), mucoadhesion force (18.05 N/cm2), and drug content (6.22%). Furthermore, the results demonstrated that HPMC polymer improved the characteristics of the films, modified the bioadhesiveness, and finally, enhanced elasticity. However, DSC thermogram failed to show any crystalline drug substance in the films except for F1 (immediate release) and the endothermic peak of ISDN was absent in F2 and F3 films. Therefore, the drug which was entrapped into the film was in an amorphous or disturbed-crystalline phase of the molecular dispersion or dissolved in the melted polymer in the polymeric matrix. Moreover, the drug release from the films was faster compared to the tablet® (P<0.05). Conclusion: In general, the formulation of F1 was observed to be an appropriate candidate for developing the sublingual film for the remedial use.

Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films

“…The retained melting peak of FXS in the physical mixture indicates the absence of physical interaction between the drug and the selected excipients (Ahuja et al, 2015 ). A slight early onset of endotherm was observed in O-SF at 109.14 °C indicating a complete overlap of the polymer peak with the drug peak (Fathei et al, 2019 ). This might be due to the miscibility of drug with excipients (Ahuja et al, 2015 ).…”

“…O-SF compared to drug suspension in buffer were tested for FXS permeation using sheep sublingual tissue (Fathei et al, 2019 ). The sublingual mucosa of Rahmani sheep having average age of 6 months and weight of about 32 kg were obtained from a local slaughterhouse.…”

“…It was held to the support by a plastic ring (Gavini et al, 2005 ). The drug suspension or O-SF moistened with 1 ml of PBS (Talekar et al, 2019 ) (each containing 8 mg of drug) were placed on the epithelial smooth surface of sheep mucosa (Fathei et al, 2019 ). In case of O-SF, it was folded to fit over the circular area of the membrane.…”

Isosorbide Dinitrate Orally Disintegrating Films Cyclodextrins/HPMC Based: Mechanical, Optical, and Physicochemical Studies

“…As a result, these thin films have the potential to accelerate the onset of the action of the drugs, lower the drug strength, and enhance the efficacy and safety profile of some drugs. From the market perspective, new drug delivery technologies offer opportunities to extend revenue life cycles for pharmaceutical companies whose drug patents are about to expire, and who are vulnerable to generic competition [1][2][3][4][5][6][7].…”

“…Hydrodispersible polymers are the main components of the oral films. Both natural and synthetic polymers, alone or in blends, are used to fabricate films with the desired properties [6][7][8][9].…”