Formulation, Optimization and Evaluation of Silymarin Nanosponges

Ann Maria, Sunny (2018) Formulation, Optimization and Evaluation of Silymarin Nanosponges. Masters thesis, College of Pharmacy, Sri Ramakrishna Institute of Paramedical Sciences, Coimbatore.


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Nanosponges are microscopic particles with few nanometers wide cavities, in which a large variety of substances can be encapsulated. These particles possess the ability to carry both lipophilic and hydrophilic substances and thereby improving the solubility of poorly water soluble molecules. Drugs encapsulated within the nanosponge pores are shielded from premature destruction and stability of drug is enhanced. Silymarin, a potential phytochemical compound obtained from the seeds of Silybum marianum (milk thistle) plant has been used as a hepatoprotective agent, and shows strong anti-oxidant effect. Silymarin has been extensively studied in vitro and in vivo for its cancer chemopreventive potential against various cancers. The high incidence of administration of silymarin together with its short half-life and poor bioavailability proposed great scope for the proposal of nanoparticulate drug delivery systems. Various nanoformulation platforms employed as delivery vehicles for silibinin possess a major drawback in their low silibinin payloads. Main objective of this study was to formulate Silymarin loaded nanosponges using different polymers to target cancer cells (breast cancer, colorectal cancer or oesophageal cancer) and release the drug in a controlled manner. This formulation reduced the side effects, minimized the dosing frequency and dose. The present work aimed at formulating Silymarin nanosponges with two different types of polymers namely hydrophilic and hydrophobic polymers using emulsion solvent diffusion method. This method was simple and cost effective. Preformulation studies were carried out to find out the solubility of Silymarin. Solubility test gave an idea that silymarin is not water soluble but soluble in solvents like acetone, dichloromethane etc. FTIR and UV spectral studies authenticate the spectra obtained with the sample drug matched with standard pure drug. UV spectra gave the maximum absorption peak at 288nm. The comparison of FTIR spectra of Silymarin and mixture of Silymarin and polymer confirms that there is no appearance of additional new peaks and disappearance of existing peaks from that of the drug. This indicates that there is no interaction between the drug and polymer used in the study. Formulation was carried out by emulsion solvent diffusion method. Trial batches indicated that hydrophilic polymers are not suitable for the Silymarin nanosponges. The hydrophilic polymers produced no yield or very less yield. Hydrophobic polymers produced good formulations. Ethyl cellulose and eudragit were selected for further studies. Scanning electron micrograph of the prepared nanosponges at different magnification showed that the nanosponges were porous with a smooth surface morphology and spherical shape. The spongy and porous nature of nanosponges was clearly observed in the SEM images. Particle size and zeta potential was determined by Malvern Zeta sizer. The particle size analysis confirmed that the prepared sample were in the nanometer range. Average particle size obtained for the formulations F4 and F9 were 4097nm and 3811nm. Zeta potential values of nanosponges indicated that the formulated nanosponges are stable. The amount of drug being entrapped in nanosponges was calculated and all the prepared nanosponges were found to possess very high entrapment efficiency. From the in-vitro release data from the dialysis bag diffusion method it was found that formulations F1, F2, F6 and F7 showed the best release of 89.90%, 88.79%, 90.19% and 87.10% respectively at the end of 48 hours. Increase of drug release was observed as a function of drug: polymer ratio. It was observed that the drug release decreased with an increase in the amount of polymer for each formulation. This is because the newly developed nanosponges is believed to exhibit a core shell structure with a hydrophobic core formed by ethyl cellulose(F1-F5) and eudragit(F6-F10) and a hydrophilic shell formed by PVA macromolecules. The formulations were optimized by general full factorial design using Minitab 18 statistical software. Effect of polymer type and drug: polymer ratio on the drug release pattern of formulated Silymarin nanosponges on drug release was studied. It was found that the polymer type has no significant effect on the drug release pattern whereas the drug: polymer ratio has a significant effect on the release pattern of the drug. As the drug: polymer ratio increases the release of drug from the nanosponges decreases. Even though the drug release from both Silymarin- ethyl cellulose nanosponges (F5) and Silymarin- eudragit nanosponges (F10) are similar, the F5 formulation is selected as the optimum formulation due to its comparatively higher yield. The data obtained from the in vitro release study was fitted to the models which were used to find out the mechanism of drug release from silymarin nanosponges. The in vitro release model best fitted to Higuchi release order. This was confirmed by plotting percentage cumulative drug release and square root of time and r2 value ranges between 0.8477 and 0.9888. It is observed that formulation F1, F2, F6, F7 and F8 followed Fick’s law of diffusion and rest showed an anomalous behaviour. The Silymarin nanosponges can be formulated by cost effective and easy emulsion solvent diffusion method using hydrophobic polymers such as ethyl cellulose and eudragit. The formulated silymarin nanosponges can be used in the treatment of cancer such as prostate or colorectal cancer. This can be targeted to the cancer cells and produce sustained drug delivery which in turn reduces the dose, frequency of administration and the side effects.

Item Type: Thesis (Masters)
Additional Information: (Register no: 261610151)
Uncontrolled Keywords: Silymarin Nanosponges ; Formulation ; Optimization ; Evaluation
Subjects: PHARMACY > Pharmaceutics
Depositing User: Subramani R
Date Deposited: 15 Jun 2019 03:19
Last Modified: 15 Jun 2019 03:19

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