(T1130-09-56) Nicotine Hydrogen Tartrate Containing Fast Dissolving Films: Formulation and In Vitro Evaluation

Purpose: Fast dissolving films (FDFs) have gained attention as an innovative drug delivery system due to their ease of administration, rapid disintegration, and potential for improved patient compliance—particularly in populations with difficulty swallowing conventional dosage forms. Smoking cessation remains a major public health goal, as tobacco use is a leading cause of preventable morbidity and mortality worldwide. Nicotine replacement therapies (NRTs) play a critical role in supporting individuals attempting to quit smoking by reducing withdrawal symptoms and cravings. While the current NRTs (e.g., gum, lozenges, patches) deliver nicotine too slowly to relieve sudden cravings, limiting their effectiveness during the initial craving phase. Fast-dissolving films offer rapid nicotine release through the oral mucosa, providing quicker craving relief and better mimicking the speed of smoking. This study focuses on the formulation and in-vitro evaluation of fast dissolving films containing nicotine hydrogen tartrate (NHT), a salt form of nicotine suitable for oral mucosal delivery. The goal is to develop a convenient, effective, and patient-friendly dosage form that can deliver nicotine rapidly, supporting smoking cessation efforts.

Methods: In this study, fast-dissolving films (FDFs) were formulated using varying concentrations (2%, 3%, and 4% w/w) of hydroxypropyl methylcellulose (HPMC) E3 LV and E5 LV, along with plasticizers PEG 400 and propylene glycol (PG) at 10%, 20%, and 30% w/w. The films were prepared using the solvent casting method and cut to a final size of 2 cm × 2 cm. The formulations were evaluated for key parameters including in-vitro dissolution, disintegration time, tensile strength, folding endurance, and surface morphology. In addition, DSC, FTIR, and XRD analyses were performed to assess excipient compatibility and characterize the solid-state properties of the films.

Results: The prepared formulations had weights ranging from 37.4 ± 4.76 mg to 75.85 ± 9.19 mg and thicknesses from 0.080 ± 0.008 mm to 0.165 ± 0.025 mm. All formulations were easy to pour, spread uniformly, remove, and dried consistently. Morphological evaluation revealed that higher concentrations of PEG 400 produced sticky films, likely due to a moist surface layer, which may affect appearance and handling. All formulations showed a characteristic release profile: rapid initial release, followed by a slower phase, reaching a plateau around 10 minutes. Figure 1 compares the dissolution profiles of the optimized FDF formulation (52G1), NHT powder, and the commercial product Nicorette® chewing gum, confirming the faster release of 52G1. At the 5-minute mark, drug release was negatively affected by polymer concentration, while the type and concentration of plasticizer had minimal impact. In-vitro disintegration time increased with both higher polymer concentrations and the use of higher-viscosity grades (Figure 2). Tensile strength showed a slight direct correlation with polymer concentration but an inverse correlation with plasticizer concentration (Figure 3). Films prepared with HPMC E5 LV had higher tensile strength than those with HPMC E3 LV. Films without plasticizer were brittle and easily broke when handled, highlighting the necessity of incorporating a plasticizer to enhance mechanical strength. Folding endurance was consistently higher in films containing HPMC E5 LV compared to those with HPMC E3 LV across all concentrations. Films plasticized with PEG 400 had lower folding endurance than those with propylene glycol (PG). e optimized formulation 52G1 demonstrated 81.81%±3.07 % drug release in 5 minutes, 19.18±2.33 seconds of disintegration time, 22.22±0.89 kg/mm² tensile strength and 9.67±0.58 of folding endurance. Characterization studies via DSC and FTIR confirmed no significant interactions between NHT and other formulation components. XRD and DSC analyses indicated the presence of NHT in an amorphous form. FTIR spectra further supported the absence of chemical interactions in the final formulation.

Conclusion: Oral fast-dissolving polymeric films of NHT were successfully developed using the solvent casting method. Disintegration time increased with higher polymer concentrations, with the maximum time reaching approximately 90 seconds, highlighting the films’ effectiveness for rapid drug release. Polymer concentration had a strengthening effect, while plasticizer concentration reduced the tensile strength of the films. Films prepared with higher-viscosity grade polymers consistently demonstrated greater tensile strength than those made with lower-viscosity grades. No crystallization peaks were observed in DSC and XRD showed drug was present in amorphous form in formulation. These findings suggest that the nicotine-loaded fast-dissolving films present a promising delivery system for nicotine replacement therapy, offering rapid craving relief in support of smoking cessation.

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Figure-1: Comparison of release of NHT from formulation 52G1, NHT reference (powder) and from Nicorette chewing gum

Figure-2: Effect of Polymer Type and Concentration on disintegration time

Figure-3: Effect of plasticizer type and plasticizer concentration on tensile strength of films fabricated using HPMC E3 LV and HPMC E5 LV