Formulation and Evaluation of 5-Fluorouracil and N-Acetylcysteine Loaded Microsponges Drug Delivery System

Nasal drug delivery via polymer systems has been proposed to be prevailing in the type of controlled drug delivery devices both in present and future. For scientific as well as economic reasons, such delivery systems have potential advantages which include enhanced therapeutic response, predictable rate of release at the targeted site, less side effects and extent of absorption and better patience compliance. In the present work an nasal delivery microsponges formulation of a potent anticancer drug, 5- Fluorouracil and Chemopreventive drug N-Acetylcysteine has been developed. The study includes formulation and evaluation of 5FU-NAC microsponges. The idea behind developing a nasal polymeric microsponges delivery system of 5FU-NAC was to deliver 5FU-NAC in a controlled release pattern for a long period of time up to 12 hours in order to reduce dose frequency and improve patience compliance. Box-Behnken statistical design with 3 factors, 3 levels and 17 runs were employed for the optimization study using design-expert software version 12. The variables stirring speed, polymer Ethyl cellulose, Dichloromethane were main factors that impacted the particle size, entrapment efficiency and Mucoadhesion in our microsponges formulation in our preliminary experiments. To investigate the impact of stirring speed(A), Ethyl cellulose (B) and dichloromethane (C) were selected as independent variables and they were set at high, medium and low level on the basis of the results of initial trials. In accordance with the design, 17 microsponge formulations were prepared and characterized for particle size (R1), entrapment efficiency (R2) and Mucoadhesion (R3). However, five set of formulations were selected from given 17 runs of formulations since those five showed response.[F1,F4,F7,F11,F14]. From the five optimized formulation one formulation [F7] was selected randomly. and it was characterized. The ratio of drug: polymer for the formulation of 5FU-NAC microsponges was varied in formulation and then the microsponges were evaluated for drug content, encapsulation efficiency, FTIR, particle size, zeta potential, x -ray diffraction study, morphological study by SEM, and invitro drug diffusion study using cellophane membrane and nasal mucosal membrane of goat, mucoadhesion study by using mucosal membrane, swelling index. The results obtained from the optimization technique was incorporated in our experimental value and signified that stirring speed of 1300 rpm, Ethyl cellulose of 3g and dichloromethane of 15ml was found to produce microsponges with good physical and morphological characters. Therefore, our optimized formulation F7 was significantly in accordance with the formulation derived from the optimization technique, values varying little, The release rate of drug from varying concentrations of polymeric microsponge shows that the release of drug increase with increasing concentration of polymers. The optimized formulation F7 has the good drug diffusion rate in the treated cellophane membrane. And nasal mucosa of goat. And give prolong drug release upto 12 hours. Because ethyl cellulose polymer control the drug release rate. The microsponges diffusion profile was compared with that of pure drugs diffusion profile. This studies shows that, the drug release profile was greatly extended by microsponges formulation.it shows prolonged drug release of 5FU-NAC. The drug was released from the microsponges formulation, threw the pores present in the surface of the microsponges. The pores was characterized by the evaporation of solvent dichloromethane from the internal phase. This pores plays a vital role in drug release mechanism. The optimized formulation F7 , have good swelling index, so the microsponges formulation easily attached to the membrane. Greater swelling property is mainly due the presence of polymer concentration in higher rate. Ethyl cellulose have property of good swelling capacity. The optimized formulation F7, has good Mucoadhesion property so the microsponges formulation can be easy stick over the mucosal membrane of nasal track. This Mucoadhesion is mainly due to the ethyl cellulose polymer concentration. After the formulation it was filled in hard gelatin capsule. And it was used by dry powder inhaler device like nebulizer or rotacap. According to the patient‟s convenience. to deliver the content directly to the lung. Repeated deep inhalation minimize the dose lose due dose deposition to the surface of the DPI device. However, in vivo experiments are essential to establish the actual usefulness of these microsponges. CONCLUSION An nasal delivery microsponges formulation of 5FU-NAC was formulated using polymer Ethyl cellulose. From the study the following conclusion can be drawn. The amount of internal phase that is Dichloromethane was selected at 30ml depending on the previous researches suitable for the preparation of microsponges and the external phase was found to be distilled water of 100ml containing PVA. The concentrations of the polymers required to produce microsponges with good physical and morphological characteristics was found to be 3g of Ethyl cellulose in accordance the optimum amount derived from the optimization technique with little variation in the main formulation. The stirring speed was found out to be 1300rpm for 2 hour from the optimization technique to check how it affects the particle size, however it was not inputted in the main formulation as it can controlled while in the experiments. The ratio of drug: polymer required to produce microsponges with good encapsulation efficiency was found to be at 1:1.5 below this ratio, microsponges formed had low capacity encapsulation efficiency of drug and low production yield and above thus range, there was also further increase in the encapsulation efficiency but the particle size increased. Hence, it was concluded that at 1:1.5 drug: polymer ratio, was an optimum ratio of polymer ratio to produce good microsponges. F7 formulation shows good swelling property. so the mucoadhesion also good to produce drug release in proper way. By the drug release studies of formulation F7, It was concluded that the release profile was in controlled fashion.. Finally, we may conclude that formulation F7 was best formulation in the class of Ethyl cellulose of 3g as retarding polymers. Microsponge formulation shows better controlled drug release profile as compared to that of pure drug. It states that the duration drug release from the single dose is increased. So we can minimize the dosing frequency. We can minimize the drug wastage. By directly delivering the microsponges to the affected site (lungs) by intra nasal drug delivery device, we can minimize the drug wastage; reduce the toxic effect produced by the drug to the normal healthy tissues