Development of lipidic drug delivery system for bioavailability improvement of poorly water-soluble antihypertensive drug
Abstract
Felodipine nanosponges were prepared successfully by using of two different polymers, namely hydrophobic polymers (ethyl cellulose, Eudragit) by an emulsion solvent diffusion technique. This production method has been found to be simple, requires no special equipment and is scalable. Preformulation studies were performed to determine the solubility of felodipine. The solubility test gave insight that felodipine is not soluble in water but soluble in solvents such as ethanol, methanol, dichloromethane, etc. FTIR and UV spectral studies confirm the spectra obtained with the sample drug, which was compared with a standard pure drug. UV spectra gave the highest absorption peak at 364 nm. Comparison of the FTIR spectra of felodipine and nanosponge preparations confirms that no new peaks arise from the drug and no existing peaks disappear. This indicates that there is no interaction between the drug and the polymer used in the study. Scanning electron microscopy analysis of the prepared nanosponges at different magnifications showed that the nanosponges were porous, with a smooth surface morphology and a spherical shape. The spongy and porous nature of the nanosponges was clearly observed in the SEM images. Particle size and zeta potential were determined using a Malvern Zetasizer. Particle size analysis confirmed that the prepared sample was in the nanometer range. The average particle size of formulations F2 was 5112 nm. The Zeta potential values of the nanosponge showed that the prepared nanosponges are stable. The amount of drug trapped in the nanosponges was calculated and it was found that all prepared nanosponges have high blocking efficiency. From the in vitro release data of the diffusion method, it was found that formulations F2 showed the best release of 40.87% at the end of 12 hours. An increase in drug release as a function of drug to polymer ratio was observed. It was observed that drug release decreased with increasing amount of polymer in each formulation. This is because the newly developed nanosponges probably have a core-shell structure with a hydrophobic core formed by ethyl cellulose (F1-F3) and Eudragit (F4-F6) and a hydrophilic shell formed by PVA macromolecules. For drug release, the effect of polymer type and drug:polymer ratio on the drug release from formulated felodipine nanosponges was investigated. The type of polymer was found to have no significant effect on the drug release pattern, while the drug:polymer ratio had a significant effect on the drug release pattern. As the ratio of drug to polymer increases, drug release from the nanosponges decreases. Data obtained from the in vitro release study were fitted to models used to elucidate the release mechanism of felodipine from the nanosponges. The in vitro release model best fits the Korsemeyar-Peppas model. The range of r2 values for these models is 0.994. It is found that formulation (F2) followed the anomalous behavior of non-Fickian diffusion. Felodipine nanosponges can be prepared by a cost-effective and simple emulsion solvent diffusion method using hydrophobic polymers such as ethyl cellulose and Eudragit. The formulated felodipine nanosponges can be used in the treatment of hypertension and produce the drug continuously, which in turn reduces the dose, frequency and side effects. Felodipine nanosponges were successfully prepared using two different polymers, namely hydrophobic polymers (ethyl cellulose, Eudragit) by an emulsion solvent diffusion technique. The solubility test gave an idea that felodipine is not soluble in water but soluble in solvents such as ethanol, methanol, dichloromethane, etc. FTIR and UV spectroscopic studies confirm the spectra obtained from the sample drug, which was compared with the pure standard drug. Comparison of the FTIR spectra of felodipine and nanosponge preparations confirms that no new peaks arise from the drug and none of the existing peaks disappear. The amount of drug remaining in the nanosponges was calculated and it was found that all the prepared nanosponges have a strong inhibitory effect. Regarding drug release, the effect of polymer type and drug:polymer ratio on the drug release from formulated felodipine dosage sponges was investigated. It was observed that the type of polymer had no significant effect on the drug release pattern, while the drug to polymer ratio had a significant effect on the drug release pattern. As the ratio of drug to polymer increases, drug release from the nanosponges decreases. Data from the in vitro release study were fitted to models used to elucidate the release mechanism of felodipine from the nanosponges. The range of r2 values for these models is 0.994. Formulation (F2) was found to follow the anomalous behavior of nonFickian diffusion. Felodipine nanosponges can be prepared by a cost-effective and simple emulsion solvent diffusion method using hydrophobic polymers such as ethyl cellulose and Eudragit. The formulated felodipine nanosponges can be used in the treatment of hypertension and produce the drug continuously, which in turn reduces the dose, frequency and side effects.
