Affecting factors on release kinetics of caffeine as a transdermal food supplement from electrospun polyvinyl alcohol or polycaprolactone mats

Abstract

Caffeine (1, 3, 7-trimethylxanthine) is an alkaloid naturally found in a variety of foods and drinks, such as tea, coffee beans, and chocolate. It is a central nervous system stimulant that improves alertness; therefore, it is also added to beverages and food supplements. In general, caffeine is taken orally since this route is simple, cost-effective and convenient. After oral consumption of caffeine, it achieves peak plasma concentrations within 30 to 120 minutes. Transdermal delivery offers an attractive alternative to oral delivery. It shows controlled, sustained release and avoids first-pass metabolism. Nanofibers produced by the electrospinning technique are gaining attention for transdermal delivery of bioactive molecules due to their high surface-to-volume ratio, porosity and enhanced stability. Caffeine-loaded nanofiber studies produced by the electrospinning method for transdermal release are limited in the literature. In this thesis, transdermal mats were designed for caffeine delivery through the skin. Caffeine-loaded transdermal mats were produced by electrospinning using different amounts of caffeine, polyvinyl alcohol (PVA) or polycaprolactone (PCL). Feed solution properties, electrospun mat characteristics, encapsulation efficiency and in vitro release were analyzed. Surface tension, electrical conductivity and viscosity were measured as 41.05 ± 0.53 mN/m, 0.7050 ± 0.01 mS/cm, and 0.30 ± 0.01 Pa.s for %2 (w/w) caffeine containing PVA solution; 40.96 ± 0.81 mN/m, 0.5700 ± 0.01 mS/cm, 1.12 ± 0.01 Pa.s for %5 (w/w) caffeine containing PVA solution; 29.69 ± 0.00 mN/m, 0.0035 ± 0.00 mS/cm, 0.09 ± 0.01 Pa.s for % 2 (w/w) caffeine containing PCL solution; 27.87 ± 0.11 mN/m, 0.0030 ± 0.00 mS/cm and 33.26 ± 7.64 Pa.s for % 5 (w/w) caffeine containing PCL solution. Nanofiber prepared from PVA solution containing 2 % (w/w) caffeine was coded as PVA-2; nanofiber prepared from PVA solution containing 5 % (w/w) caffeine was coded as PVA-5; nanofiber prepared from PCL solution containing 2 % (w/w) caffeine was coded as PCL-2 and nanofiber prepared from PCL solution containing 5 % (w/w) caffeine was coded as PCL-5. According to their thickness, the thinner nanofiber was coded as TN, and the thicker nanofiber was coded as TK. PVA-2-TN, PVA-2-TK, PVA-5-TN, PVA-5-TK, PCL-2-TN, PCL-2-TK, PCL-5-TN and PCL-5-TK are the samples that were obtained. The obtained electrospun nanofibers were characterized using scanning electron microscopy (SEM). SEM images of electrospun mats showed the diameter and morphology of the nanofibers. The results showed that the mean diameters of PVA-2, PVA-5, PCL-2 and PCL-5 were 144.50 ± 19.24, 207.76 ± 15.66, 189.50 ± 35.31 and 298.54 ± 53.28 nm, respectively. Increasing the caffeine content in nanofibers increased the nanofiber diameter. The morphologies of the nanofibers showed that the samples containing PVA polymer exhibited a uniform structure. Furthermore, the addition of caffeine caused bead formation and non-uniform structure in the samples containing PCL polymer. The suspensions of all nanofiber samples have a zeta potential value between -10 mV and +10 mV. The samples can be considered neutral. Contact angle and swelling ratio measurements were carried out to characterize electrospun mats. All PVA containing mats were hydrophilic due to having a lower contact angle than 90 °. PCL containing mats showed hydrophobic behaviour. The swelling ratio of PVA polymer containing nanofibers was not determined, the PVA polymer containing nanofibers quickly formed a transparent form because of the high hydrophilicity of PVA. The swelling ratio increased significantly as the caffeine content in PCL containing nanofibers increased. The increase in the swelling ratio can be explained by the hydrophilic structure of caffeine. The melting behavior of electrospun mats was investigated by differential scanning calorimetry (DSC). The melting point of the caffeine was obtained at 238.28 ± 0.21 °C. The PVA-5, PCL-2 and PCL-5 nanofibers showed a peak at approximately 220 °C, 178 °C and 186 °C, which may be related to the melting temperature of caffeine, while the PVA-2 sample did not show a peak. This can be explained by the fact that the caffeine in PVA-2 is in amorphous form while the others are in crystallized form. The encapsulation efficiencies were 58.95 ± 12.19 %, 39.55 ± 5.74 %, 82.82 ± 0.23 % and 39.10 ± 4.55 % for PVA-2 , PVA-5 , PCL-2 and PCL-5, respectively. In vitro caffeine release studies were carried out using a Franz diffusion cell. The effects of caffeine amount, polymer type and nanofiber thickness on caffeine release from nanofibers were investigated. In vitro release results at 10 min showed that as the amount of caffeine in nanofibers increased and the thickness decreased, the cumulative release from the electrospun mats increased. In addition, the in vitro cumulative release at 400 min was found to be higher in nanofibers containing PCL and more caffeine content. Increasing the thickness also increased the in vitro cumulative caffeine release. In vitro release data from nanofibers was fitted to kinetic models to investigate the caffeine release kinetics of nanofiber mats. Zero-order model was found to fit the caffeine release profile from PCL-5-TN and PCL-5-TK nanofibers. The fit to the zero-order model indicated that the release rate of caffeine is independent of the amount of caffeine in the nanofiber, which is desirable as it prevents burst release. The release behaviours of PVA-5-TN, PVA-5-TK and PCL-2-TK fitted Ritger and Peppas equation. This model is used for drug release from polymeric systems. For PVA-2-TN, PVA-2-TK and PCL-2-TN nanofibers, the best kinetic model was the Higuchi model. This model demonstrated the controlled release of caffeine from transdermal patches.