Unfortunately, there are number of potential drug candidates that have poor aqueous solubility is increasing progressively. The invention of Nanosponges has become a significant step towards overcoming these problems.
These small sponges can circulate around the body until they encounter the target site and stick on the surface and began to release the drug in a controlled and predictable manner which is more effective for a particular dosage form.
The purpose of this research was to prepare Nateglinide loaded Nanosponges for controlled release of drug, and to improve the aqueous solubility of nateglinide, reduce dosing frequency and to improve the patient compliance.
Nateglinide is a poorly soluble drug with a short half life, thus selected as a model drug for Nanosponge Drug Delivery System and to release the drug in a controlled manner for prolonged period.
Nateglinide is formulated as Nanosponges by Emulsion Solvent Diffusion method using
Ethyl Cellulose as polymer and Polyvinyl alcohol as a stabilizer.
❖ The physical compatibility of Nateglinide with excipients was studied. The drug and exicipients were physically compatible with each other.
❖ The chemical compatibility studies of Nateglinide with excipients was carried out using FT-IR Spectrometer. It revealed that no interaction between the drug and excipients.
❖ Melting point of drug was determined. It matches with the standard value.
❖ Calibration curve was plotted for Nateglinide and it was found that the solutions show linearity (0.999) and obeyed Beer-Lambert’s law.
❖ Solubility of pure drug was determined. Nateglinide pure drug in distilled water and phosphate buffer pH 6.8 was found to be insoluble.
❖ Formulation study design was developed by using box behnken design (Design Expert (version 8.0.7.1., Stat Ease.,Inc)), the formulation design were predicted and statistically analysed.
❖ The independent variables selected were Ethyl cellulose (A), Polyvinyl alcohol (B) and Stirring speed (C) and the dependent variable choosen were Particle size (Y1), PDI (Y) and Entrapment efficiency (Y3).
❖ The formulations were optimized using Box Behnken design by comparing the predicted values with the observed values.
❖ The design predicted the values of optimized formulation which was then formulated and evaluated.
❖ The optimized formulation was evaluated for FT-IR Study and it is clearly evident that the optimized Nanosponge formulation showed the presence of characteristics bands of Nateglinide. This indicates the absence of chemical interaction between the Nateglinide and the excipients.
❖ The formulated Nateglinide loaded nanosponge was evaluated for their percentage yield and was found to be 96.98%.
❖ The solubility of optimized formulation in distilled water and phosphate buffer pH 6.8 was compared with that of pure drug and concluded that optimized nanosponge shows increased solubility compared to pure drug.
❖ The UV-visible spectrophotometric method was used to determine the drug content of optimized nanosonge formulation. The drug content was found to be 96.91%.
❖ The entrapment efficiency of the optimized formulation was determined and their entrapment efficiency of the formulations was observed to be 90.49%.
❖ The prepared optimized nanosponge shows significantly higher dissolution rate compared to that of pure drug. It was observed that the drug release rate decreased by the concentration of polymer.
❖ In vitro release of optimized formulation showed a rapid initial burst, followed by a very slow drug release.
❖ The optimized formulation were characterized for surface morphology, particle size analysis and zeta potential.
❖ The shape and surface morphology of optimized formulations were observed in SEM.
It shows that the Nanosponges were spherical with numerous pores on their surface, uniform and spongy in nature. The presence of pores may be due to the diffusion of the solvent (dichloromethane).
❖ The particle size distribution and polydispersity were carried out using Horiba Scientific particle size analyzer. The mean particle size and Z average of optimized formulation was found to be 181.4 nm and 264 nm (within nanometric range).
❖ Polydispersity of optimized formulation was found out to be 0.326, indicating uniformity of particle size within formulation.
❖ The zeta potential study was done by zeta sizer. The zeta potential for the optimized formulations was found to be be - 33.7mV which showed that the formulation is stable.
❖ Flow property measurements (Bulk density, Tapped density, Angle of repose, Carr’s index and Hausner’s ratio) were studied for Nateglinde pure drug and optimized Nanosponge. It revealed that the flow property of pure drug was very poor, but the optimized Nanosponge has good flow property.
❖ The release kinetics of the optimized formulations was fitted to various kinetic models and the optimized formulation was best fitted to Zero order kinetics. The zero order kinetics explains the controlled release of the prepared Nanosponges over the period of 12 hours.
❖ Higuchi plot show linearity, which indicates the rate of drug release through the mode of diffusion and the slope of the Korsmeyer Peppas plot (0.636) indicating the diffusion was anomalous diffusion (Non Fickian diffusion).
❖ Thus, the release kinetics of the optimized formulation was best fitted into Higuchi model and showed zero order drug release with Non Fickian diffusion mechanism.
❖ The optimized formulation was subjected to room temperature, accelerated stability study (temperature 40°C±2°C and RH 75±5%) and refrigerator temperature (4±20C).
The results show no significant change in appearance, drug entrapment efficiency and drug content of optimized formulation after one month.
❖ The foregoing results attempt to suggest that for poorly soluble drugs like Nateglinide, Nanosponge approach would be a possible alternative delivery system to conventional oral formulation to improve its bioavailability.
FUTURE PLAN:
• The optimized nateglinide nanosponge can be loaded in capsule and evaluated.
• In vivo studies.
• Pharamcokonetics & Biodistribution studie
