Fabrication and Characterization of Fast-Dissolving Films Containing Escitalopram/Quetiapine for the Treatment of Major Depressive Disorder

Abstract

Major depressive disorder (MMD) is a leading cause of disability worldwide. Approximately one-third of patients with MDD fail to achieve response or remission leading to treatment-resistant depression (TRD). One of the psychopharmacological strategies to overcome TRD is using a combination of an antipsychotic as an augmenting agent with selective serotonin reuptake inhibitors (SSRIs). Among which, an atypical antipsychotic, quetiapine (QUE), and an SSRI, escitalopram (ESC), were formulated as a fixed-dose combination as a fast-dissolving film by coaxial electrospinning. The resultant fiber’s morphology was studied. SEM images showed that the drug-loaded fibers were smooth, un-beaded, and non-porous with a fiber diameter of 0.9 ± 0.1 µm, while the TEM images illustrated the distinctive layers of the core and shell, confirming the successful preparation of these fibers. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies confirmed that both drugs were amorphously distributed within the drug-loaded fibers. The drug-loaded fibers exhibited a disintegration time of 2 s, which accelerated the release of both drugs (50% after 5 min) making it an attractive formulation for oral mucosal delivery. The ex vivo permeability study demonstrated that QUE was permeated through the buccal membrane, but not ESC that might be hindered by the buccal epithelium and the intercellular lipids. Overall, the developed coaxial fibers could be a potential buccal dosage form that could be attributed to higher acceptability and adherence among vulnerable patients, particularly mentally ill patients.

Fast-Dissolving Nifedipine and Atorvastatin Calcium Electrospun Nanofibers as a Potential Buccal Delivery System

“…Spraybase ® (Dublin, Ireland) provided a coaxial electrospinning setup to prepare the core-shell fibers using a modified method of (12). Coaxial needles contained inner and outer needles with 0.45 and 0.9 mm diameters, respectively.…”

“…The disintegration of the blank and drug-loaded fibers was assessed using a modified method of the Petri dishes assay described in Tawfik et al [10]. Previous studies have used the Petri dishes method to evaluate the disintegration of electrospun fibers and other oral dispersible films [12,23,24]. Approximately 4 mg of each fiber mat was placed into 8 mL of pre-warmed PBS (pH 7) under gentle stirring to ensure complete detachment of the fibers.…”

“…Measurement of the drug release was performed by placing approximately 8 mg of the drug-loaded fibers into glass vials containing 20 mL of pre-warmed PBS (pH 7). The vials were kept in a thermostatically shaking incubator at 37 ± 0.1 • C and 100 rpm, according to Alkahtani et al study [12], but in a dark room. Samples measuring 1 mL were withdrawn after 2, 5, 10, 15, 30, 60, 120, 180, 240, and 300 min and replaced with equivalent volumes of pre-warmed fresh buffer to maintain the sink conditions.…”

“…Consequently, electrospun nanofibers were suggested as an alternative system which has shown considerable potential in controlling the release rate with its unique mechanical properties [11]. Furthermore, electrospun nanofibers have also proved their relatively rapid disintegration that occurs within less than two seconds, compared to other orally disintegrating films, which disintegrate in ≤30 s [10,12].…”

Weibull Modeling of Controlled Drug Release from Ag-PMA Nanosystems

“…Further, to increase drug collection/release efficiency in a nanofiber system, controlled wetting properties are desirable [ 18 ]. Thus, fiber systems are employed to reach both immediate and controlled drug release processes [ 19 , 20 ].…”