Development, in vitro Evaluation, and in vivo Study of Adhesive Buccal Films for the Treatment of Diabetic Pediatrics via Trans Mucosal Delivery of Gliclazide

Abstract

Objective Development and evaluation of bucco-adhesive films of Gliclazide for pediatric use. Methods Sixteen films were formulated using a different combination of Gelatin, Hydroxy propyl methyl cellulose (HPMC), polyvinyl alcohol, Hydroxy propyl cellulose (HPC), chitosan, polyethylene glycol, sodium alginate, and carbopol. Compatibility study for drug and polymers was conducted using differential scanning calorimetry method and Fourier transform infrared spectroscopy. All films were examined for drug content, weight variation, thickness, swelling index, muco-adhesion and folding endurance. In vitro drug release has been completed for two hours. Stability studies were conducted at 4°C, 25°C, and 40°C for selected films. The optimized formulation based on in vitro data was selected for a bioavailability study in rabbits. Results The selected film formula (carbopol 2%, HPMC 2%) did not demonstrate interactions between the drug and polymers, while it showed accepted content, muco-adhesion, and mechanical properties. The in vitro release study showed rapid and complete release of drug from films. Stability studies confirmed accepted stability of the selected film at 4°C and 25°C, but the film get hard with few particles at 40°C. The bioavailability studies conducted showed that there was 2.1 fold increase in the AUC 0-24 of selected film compared with oral tablets. Conclusion Bucco adhesive films of Gliclazide is a promising dosage form for the treatment of diabetes in children.

The Potential of Films as Transmucosal Drug Delivery Systems

“…Therefore, one of the most used applications for the transbuccal route is to treat acute conditions that require a rapid therapeutic response. In addition, due to its characteristic of immobility, the oral mucosa also presents very promising characteristics for the application of formulations that need to be retained for a longer period, such as controlled-release systems [58][59][60].…”

“…There are several commercial forms of buccal administration; these include pills, sprays, sublingual lozenges, chewing gum, films, and oral mucosal solutions [60]. Examples of products currently on the market that exploit the buccal route are buprenorphine hydrochloride soluble buccal film (Belbuca ® ), fentanyl buccal soluble film (Onsolis ® ), fentanyl lozenges (Actiq ® ), fentanyl buccal tablets (Fentora ® ), and a combination of buprenorphine and naloxone (Bunavail ® ), as well as a patch containing lidocaine (Dentipatch ® ) [61].…”

“…Buccal films, which stand out for their ease of application for adults and children, are intended for local or systemic therapeutic action. The mechanism of drug retention in this mucosa directly depends on the employed polymers in the formulation, which have different mucoadhesive properties that were previously discussed [60]. Therefore, mucoadhesive buccal films are presented as a very innovative and promising pharmaceutical form that allow the API to be absorbed in a constant and controlled way by the biological barrier due to its adhesion to the buccal mucosa and without the need to be swallowed [62].…”

“…Based on a brief analysis of these studies, the most cited polymers were HPMC, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), and sodium alginate (SA), while in relation to production methods, solvent casting was the most used technique. Finally, the health conditions mentioned were: (a) hypertension [69][70][71][72][73][74][75], (b) psychological disorders [76][77][78][79][80], (c) migraine [61,[81][82][83][84][85], (d) allergic conditions [85][86][87][88][89][90], (e) vomiting and nausea [91,92], (f) diabetes [60,93,94], (g) menopausal symptoms [95,96], (h) erectile dysfunction [97], (i) tuberculosis [98], (j) Alzheimer's [99], (k) smoking [59], (l) heart failure [100], (m) epilepsy [82], (n) HIV [101], and (o) sedation [102]. Below, we describe examples of recently published studies that were successful in the development of buccal films.…”