Development and Evaluation of Solid Lipid Nanoparticle-Loaded Oral Films for Enhanced Delivery of a BCS Class IV Drug

Abstract

Curcumin, a polyphenol derived from Curcuma longa, possesses well-established anti-inflammatory, antioxidant, antimicrobial, and neuroprotective properties. However, its clinical translation is severely constrained by its Biopharmaceutical Classification System (BCS) Class IV designation. This designation confers simultaneously poor aqueous solubility (< 0.1 mg/mL) and low membrane permeability, yielding oral bioavailability below 1%. Additional barriers including first-pass glucuronidation, alkaline pH instability, and photodegradation further impede therapeutic application. This study developed curcumin-loaded Solid Lipid Nanoparticles (SLNs) incorporated into Rapidly Disintegrating Oral Films (RDOFs) as a dual-phase oral delivery platform designed to overcome these limitations simultaneously. SLNs prepared by solvent emulsification–evaporation using Glyceryl Monostearate (drug:lipid 1:5 w/w; Tween 80:Span 80 4:1; HLB 12.9) achieved entrapment efficiency of 99.85%, mean particle size of 187.4 nm (PDI 0.182), and zeta potential of −27.84 mV, confirming near-quantitative encapsulation and adequate colloidal stability. A Quality by Design (QbD)-guided Design of Experiments (DoE) approach employing HPMC E15 and MCC 101 as Critical Material Attributes produced statistically validated polynomial models for disintegration time (R² = 0.979) and drug release (R² = 0.875). Numerical desirability optimization identified F5* (HPMC E15 = 2.64% w/v; MCC 101 = 1.71% w/v; desirability D = 1.000), which exhibited disintegration in 17.5 seconds, drug content of 93.6%, and a characteristic biphasic release profile reaching 81.7% cumulative drug release at 6 hours, following Non-Fickian anomalous transport (Korsmeyer–Peppas model; n = 0.687). Accelerated stability studies conducted over 3 months at 40°C/75% RH (ICH Q1A(R2)) confirmed retention of all critical quality attributes within acceptance limits. These findings establish the curcumin SLN-loaded oral film as a bio-pharmaceutically rational, patient-friendly, and scalable platform with significant translational potential for the management of oral diseases and neurodegenerative disorders.