FORMULATION AND EVALUATION OF NIOSOMES OF MIRTAZAPINE FOR NASAL DELIVERY

Mirtazapine is a tetracyclic anti-depressant drug approved by USFDA to treat depression. It is a BCS class II drug with a low oral bioavailability of 50% due to first pass metabolism. Thus, the purpose of this research work was to enhance the bioavailability of the drug by enhancing its solubility by incorporating it in to niosomal vesicles loaded in to an in-situ gel to enhance its permeability across the biological membrane. Niosomes were prepared by thin film hydration method and optimized by using 3 2 full factorial design. Mirtazapine loaded niosomes were further incorporated in to an Poloxamer 407 and Carbopol 934 in-situ gel base. The vesicle size of all niosomal suspension batches ranged between 202-245 nm. The vesicle size of the optimized batch F5 was found to be 211.7 nm with PDI of 0.166. The zeta potential value of F5 was found to be 0.6 mV. The % EE of all niosomal batches was found to be in a range of 69.3% – 83.7% and the cumulative % release was found to be in a range of 75.2% – 84%. DSC, XRD studies were performed for pure drug and niosomal batch F5. All the gel formulations ranged between 17.3±0.03 sec to 27.3±0.03 sec. Gelling temperature was found to be in a range of 44 o C±0.00 to 53 o C±0.0 o C and mucoadhesive results were found to be in a range of 10.3 ±0.023 to 14.5±0.060g. In-vitro drug release was found to be in a range of 68.3%-74.6%. these spectrophotometric estimation of drug by UV method at 290 nm and other studies like partition coefficient and drug- excipient compatibility studies. Partition coefficient value confirmed the lipophilicity of the drug. Compatibility studies showed that there was no interaction between the drug and excipients used in formulation. Mirtazapine showed high solubility in di-ethyl ether, which was used as solvent for formulation of niosomes. Niosomes were prepared by ether injection method, thin film hydration and sonication method of which thin film hydration was selected as ideal method as it gave low particle size and good PDI. Surfactant of different grades was screened based on their particle size, PDI and %EE, of which span 60 gave best results. Studies were carried out for screening of cholesterol: surfactant ratio and optimization of process parameters was performed with an aim to achieve maximum percent drug entrapment and uniform niosome size. 9 formulations were developed, evaluated and optimized through 3 2 full factorial design. Two factors were evaluated each at three levels. Surfactant concentration (X1) and Cholesterol concentration (X2) were selected a s independent variables. The dependent variables selected for study were particle size (Y 1 ), % EE (Y2) and PDI (Y3). Out of 9 formulations F5 was found to be best with a particle size 211.7nm and PDI 0.166, entrapment efficiency of 83.74% and in-vitro release of 82.9%. This formulation, F5 prepared by thin film hydration method was found to be best formulation to be further incorporated into an In-situ gel base of Poloxamer 407 and Carbopol 934. Formulation G5 of In-situ gel was selected as ideal formulation for convenient nasal delivery, which shows a pH of 6.26±0.06, with satisfactory and acceptable, spreadability, gelling temperature, gelling time, gel strength, mucoadhesive strength and viscosity. Histopathological studies performed, showed no signs of inflammation was the result gained. FTIR was performed for F5 niosomal batch and G5 in-situ gel batch and results revealed no in-compatibility. From in-vitro release studies formulation G5 showed a release of 72.73%. Stability studies revealed the stability of both F5 niosomal suspension and G5 gel formulation to be better at 4±2 o C as compared to room temperature.