Preparation and evaluation of fast-dissolving films of etilefrine hydrochloride for practical buccal dosing

Onishi, Hiraku; Sakata, Osami

doi:10.1080/10837450.2021.1904260

Cited by 5 publications

(5 citation statements)

References 28 publications

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“…This fast disintegration property can be a particular advantage in the reformulation of antidepressants, since dysphagia is a serious and common issue in patients with mental illness [ 17 ]. Multiple studies have reported oral mucosal (buccal and sublingual) absorption of FDFs which enhance drug bioavailability via bypassing the first-pass metabolism, and avoid pre-systemic clearance [ 18 , 19 , 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…They stated that upon in vivo investigation in rats, ET buccal aqueous droplets and buccal fast dissolving films showed a significantly higher bioavailability (2.3- and 1.15-fold), respectively, than the intragastric administration. They attributed this to that the buccal route offered an efficient approach to bypass the liver metabolism of etilefrine ( Onishi and Sakata, 2018 , Onishi and Sakata, 2021 ). These findings are also in harmony with the results of Sakata and Onishi who developed ET buccal fast dissolving tablets.…”

Section: Resultsmentioning

confidence: 99%

“…These tablets achieved similar plasma concentration–time curve to that of the previous aqueous droplets ( Sakata and Onishi 2020 ). In 2021, the same authors developed ET buccal fast dissolving films that showed a rapid drug release (more than 70 % at 2 min) and achieved higher bioavailability than the intragastric administration (1.15-fold) but didn’t achieve higher bioavailability than the previous aqueous droplets nor the fast dissolving tablets ( Onishi and Sakata 2021 ).…”

Section: Introductionmentioning

confidence: 99%

A novel oral medicated jelly for enhancement of etilefrine hydrochloride bioavailability: In vitro characterization and pharmacokinetic evaluation in healthy human volunteers

Elshafeey

El-Dahmy²

2022

Saudi Pharmaceutical Journal

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“…Complex in a 1:1 molar ratio of FLB and HP-β-CD was prepared as previously reported [ 14 ]. In brief, FLB and HP-β-CD mixture in a molar ratio of 1:1 was triturated in a porcelain mortar, then wetted with drops of acetone/water mixture and kneaded for additional 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…Orally fast-dissolving films have been widely used to deliver many drugs, which allow for gastrointestinal tract absorption after swallowing saliva containing the dissolved drug or pregastric absorption in the oral mucosa to bypass the digestive system and hepatic first-pass metabolism. Multiple studies have reported that oral mucosal (buccal and sublingual) absorption of fast-dissolving films enhances drug bioavailability via bypassing the first-pass metabolism and avoiding pre-systemic clearance [ 14 , 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

The Optimization and Evaluation of Flibanserin Fast-Dissolving Oral Films

et al. 2022

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Flibanserin (FLB) is a drug used for female hypotensive sexual desire disorder approved by the FDA in August 2015. FLB exhibits extensive hepatic first-pass metabolism and low aqueous solubility, hence poor oral bioavailability. In this study, beta hydroxypropyl cyclodextrin-FLB inclusion complexes were incorporated into orally fast dissolving films. This dosage form was expected to improve FLB aqueous solubility, which would give fast onset of action and decrease presystemic metabolism, hence improving oral bioavailability. The inclusion complex at a ratio of 1:1 was prepared by the kneading method. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffractometry (XRD) were used to confirm complex formation. The Box–Behnken design (15 different formulae of FLB fast-dissolving oral films (FLBFDOFs) were utilized for the optimization of the prepared films. The Expert Design 11 program was utilized to examine the effects of three selected factors, polymer concentration (X1), plasticizer concentration (X2), and disintegrant concentration (X3) on four responses: disintegration time (DT), initial dissolution rate (IDR), dissolution efficiency (DE), and film quality (QF). Numerical optimization was performed by minimizing disintegration time (Y1), while maximizing the initial drug dissolution rate (Y2), dissolution efficiency (Y3), and the quality factor (Y4). The statistical analysis showed that X1 has a significant positive effect on the disintegration time and a significant negative effect on IDR. While X2 and X3 produced a nonsignificant negative effect on IDR. Dissolution efficiency was maximized at the middle concentration of both X2 and X3. The best film quality was observed at the middle concentration of both X1 and X2. In addition, increasing X3 leads to an improvement in film quality. The optimized film cast from an aqueous solution contains hydroxypropyl cellulose (2%) as a hydrophilic film-forming agent and propylene glycol (0.8%) as a plasticizer and cross povidone (0.2%) as a disintegrant. The prepared film released 98% of FLB after 10 min and showed good physical and mechanical properties. The optimized formula showed a disintegration time of 30 s, IDR of 16.6% per minute, DE15 of 77.7%, and QF of 90%. This dosage form is expected to partially avoid the pre-systemic metabolism with a fast onset of action, hence improving its bioavailability that favors an advantage over conventional dosage forms.

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Preparation and evaluation of fast-dissolving films of etilefrine hydrochloride for practical buccal dosing

Cited by 5 publications

References 28 publications

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

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

A novel oral medicated jelly for enhancement of etilefrine hydrochloride bioavailability: In vitro characterization and pharmacokinetic evaluation in healthy human volunteers

The Optimization and Evaluation of Flibanserin Fast-Dissolving Oral Films

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