Hydroxypropylmethyl cellulose films crosslinked with citric acid for control release of nicotine

Hydroxypropylmethyl cellulose (HPMC) samples with varying degrees of substitution of methoxy groups (DS), mass molar substitutions of hydroxypropoxy groups (MS) and molecular weights were crosslinked with citric acid to create water insoluble films with mean thickness from (48 ± 3) µm to (127 ± 8) µm. The samples presented DS ranging from 1.5 to 2.1, MS ranging from 0.25 to 0.9 and average molecular weights (M_w) of 2.5 × 10⁵ g/mol and 6.7 × 10⁵ g/mol. Regardless of the HPMC DS, MS or molecular weight, the micrometric HPMC films presented smooth surfaces, as revealed by atomic force microscopy and surface energy (\(\gamma_{\text{S}}\)) of ~55 ± 2 mJ/m², as determined by contact angle measurements. Fourier transform infrared spectra indicated that the crosslinking reaction with citric acid was more favored for HPMC samples with high MS or with lowest modification degree. The nicotine incorporation at pH 5.5 was the highest in HPMC with high DS, low MS and low molecular weight. The release kinetics of nicotine from HPMC films was investigated at pH 2, pH 5.5 and pH 9. At these pH values nicotine is diprotonated, monoprotonated and uncharged, respectively. The experimental data were fitted with the Korsmeyer–Peppas model. In general, the release presented a quasi-Fickian behavior and it decreased as the pH increased. The release rate tended to increase as the medium ionic strength increased, indicating electrostatic interaction between nicotine and polymer matrix, particularly for HPMC with high MS. The HPMC with high MS, low DS and low molecular weight was the best one for nicotine replacement therapy, due to its quantitative release at low rates and constant amounts over time, under pH and ionic strength conditions similar to those of skin.