Formulation and Evaluation of Amlodipine Besylate Oral Dissolving Films for Improved Patient Compliance: A Quality by Design Approach Using Box-Behnken Design

Abstract

Background: Hypertension is the most prevalent modifiable cardiovascular risk factor globally, affecting approximately 1.28 billion adults. Amlodipine besylate (AML), a long-acting dihydropyridine calcium channel blocker (CCB), is one of the most widely prescribed antihypertensive agents worldwide. Despite good oral bioavailability, swallowing difficulties (dysphagia) — estimated to affect 35% of the general population and up to 60% of the elderly — significantly limit patient adherence to conventional tablet formulations. Oral dissolving films (ODF) represent an advanced drug delivery platform that disintegrates instantaneously on the tongue without water, overcoming the dysphagia barrier and potentially improving absorption through pre-gastric routes.

Objective: To develop and optimise amlodipine besylate oral dissolving films using HPMC E15 and PVA as film-forming polymers through a Box-Behnken design (BBD), and to evaluate the optimised ODF (O8) for physical and mechanical properties, FTIR and DSC characterisation, disintegration time, in vitro drug release, and ICH stability in comparison with a conventional amlodipine besylate tablet.

Methods: AML-ODFs were prepared by the solvent casting method. HPMC E15 (X1), PVA (X2), and propylene glycol (X3) concentrations were the BBD independent variables, with disintegration time (Y1) and Q1h drug release (Y2) as responses. Films were characterised for thickness, weight uniformity, drug content, moisture content, tensile strength, % elongation at break, folding endurance, and disintegration time. Drug-excipient compatibility was evaluated by FTIR (PerkinElmer Spectrum Two; KBr pellet) and DSC (TA Instruments DSC 25; 10°C/min). In vitro drug release was performed in PBS pH 6.8 (USP Apparatus II; 37°C) and compared with a conventional AML tablet. ICH Q1A(R2) stability was assessed at 25°C/60% RH and 40°C/75% RH for 6 months.

Results: The optimised ODF (O8: HPMC E15 1.5%, PVA 0.75%, PG 12%) demonstrated thickness 104.6 ± 4.8 µm, drug content 98.6 ± 1.0%, tensile strength 0.88 ± 0.04 N/mm², folding endurance 46 ± 4 folds, and disintegration time 28 ± 2 s. FTIR confirmed drug-polymer compatibility without chemical interaction. DSC showed >94% suppression of the AML melting endotherm (196.8°C; ΔH = 82.4 J/g), confirming drug amorphisation within the film matrix. Q1h drug release was 80.4 ± 2.6% — significantly superior to a conventional AML tablet (58.6 ± 3.2%; p < 0.001). ICH stability at 25°C/60% RH for 6 months confirmed acceptable physical and chemical stability.

Conclusion: BBD-optimised amlodipine besylate ODF achieved rapid disintegration (28 s), superior early drug release (Q1h 80.4%), excellent mechanical properties, and confirmed drug amorphisation, demonstrating strong potential as a patient-friendly antihypertensive dosage form for elderly or dysphagic patients with improved compliance and faster onset of drug absorption compared with conventional tablets.