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

Manal E Alkahtani,Abdul W Basit,Omar A Abu Asab,Essam A Tawfik,Alhassan H Aodah,Mine Orlu

doi:10.3390/pharmaceutics13060891

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.

Highlights

Major depressive disorder (MDD), commonly known as clinical depression, is a seriously debilitating mental disorder
MO, USA), high-performance liquid chromatography (HPLC) grade acetonitrile was obtained from PanReac AppliChem ITW Reagents (Barcelona, Spain), and escitalopram oxalate (ESC) (≥99.95%) and quetiapine fumarate (QUE) (≥99.13%) were kindly donated by Saudi Pharmaceutical Industries and Medical Appliances Corporation (SPIMACO), known as SPIMACO ADDWAEIH (Riyadh, Saudi Arabia)
Deionized water was generated by Milli Q, Millipore (Billerica, MA, USA), and was used in the preparation of simulated salivary fluid (SSF) pH 6.8 and phosphate-buffered saline (PBS) pH 7.4

Summary

Introduction

Major depressive disorder (MDD), commonly known as clinical depression, is a seriously debilitating mental disorder. It is one of the most common psychological diseases, affecting more than 264 million people worldwide [1]. The manifold etiology of depression involves genetic, biological, and psychosocial factors. It has been described that the pathophysiological mechanisms of the disease include monoamine deficiency (depletion of the neurotransmitters serotonin, norepinephrine, and dopamine in the central nervous system) and the hyperactivity of the hypothalamic–pituitary (HPA) axis [2]. The pharmacological approach is effective for the management of the disease; there are different classes of antidepressants among which selective serotonin reuptake inhibitors (SSRIs) are considered as the first-line treatment approach [3]. The pharmacological approach is effective for the management of the disease; there are different classes of antidepressants among which selective serotonin reuptake inhibitors (SSRIs) are considered as the first-line treatment approach [3]. 4.0/).

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Results

Conclusion