Formulation and optimization of duloxetine hydrochloride buccal films: in vitro and in vivo evaluation

Abstract

Duloxetine hydrochloride (DH) is a serotonin-norepinephrine reuptake inhibitor (SSNRI) indicated for the treatment of depression. Duloxetine suffers from reduced oral bioavailability (≈50%) due to hepatic metabolism. This study aims to develop DH buccoadhesive films to improve its bioavailability. DH buccoadhesive films were prepared adopting the solvent casting method using hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA). The prepared films were evaluated for weight uniformity, drug content, surface pH, swelling index, mucoadhesion strength and drug release percentages. Accelerated stability and bioavailability studies in healthy human volunteers were also performed for the selected films. Results of the evaluation tests showed that the optimum physicochemical characters were obtained by the films prepared with 2% HPMC using 10% propylene glycol (F2 films). Accelerated stability studies revealed that DH showed proved stability throughout the experiment time. DH bioavailability from F2 films was determined and compared with that of the marketed oral capsules (Cymbalta^® 30 mg). The pharmacokinetic results showed that C_max for F2 was higher than the market product. In addition, ANOVA analysis showed that a T_max of F2 film was significantly lower, while, the AUC_0-72 of F2 was significantly higher than that of Cymbalta capsules. The percentage relative bioavailability of DH from F2 was found to be 296.39%. Therefore, the prepared buccal films offer an alternative route for the administration of DH with the possibility of improving its bioavailability.

Keywords: Buccoadhesive films; accelerated stability; bioavailability; drug release; duloxetine hydrochloride; mucoadhesion.

Figure 1.

Release profiles of DH films prepared with (A) 10% PG (F1–F8) and (B) 30% PG (F9–F16).

Figure 2.

Release profile of DH from the freshly prepared and stored F2 films in SSF (pH 6.8).

Figure 3.

Mean plasma concentration–time profiles of DH after oral administration of Cymbalta^® capsules and buccal administration of F2 films to human volunteers.