Rahul Pratap Singh. et al. / International Journal of Biopharmaceutics. 2013; 4(1): International Journal of Biopharmaceutics

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1 49 e- ISSN Print ISSN International Journal of Biopharmaceutics Journal homepage: IJB NIMESULIDE LOADED MICROPONGES: IN-VITRO AND EX-VIVO EVALUATION Rahul Pratap Singh* 1, Sonali Singh 1, DR. S.K. Prajapati 2, Gyanendra Kumar Saxena 3 1 Institute of Pharmacy, Bundelkhand University Jhansi (U.P.) India. 2 Institute of Medical Sciences, Banaras Hindu University, Banaras (U.P.) India. 3 Faculty of Pharmacy, Naraina Group of Institution, Kanpur (U.P.) India. ABSTRACT Acute inflammation is commonly known as Ostreo arthritis in elderly patients for both men women all over the world. Therefore this study was undertaken to controlled release of Nimesulide. In this study, we have prepared nimesulide microspongic formulaton by using quasi-emulsion diffusion method. The preparations were prepared in different- different drug and polymer ratio. These microspongic formulations were given better controlled drug release action in comparison to convention gel. Nimesulide loaded microspongic gel shows a better result during inflammation treatment of paw edeama in rat. The current study as an attempt at better controlled drug release and response of nimesulide in inflammation diseases in rat. Hence, monitoring of these parameters would be beneficial following controlled release of nimesulide gels. Key words: Microsponges, Nimesulide, Eudragit RS 100, Carbopol 934. INTRODUCTION Nimesulide loaded microspongic gel are very suitable medication in inflamation disease because this type formulation given better result in comaprison to conventional nimesulide loade gel. Nimesulide loaded microspongic gel gives better controlled release action in comapare to marketed gel (Comoglu T et al., 2002; Kawashiama et al., 1992). Nimesulide is a medication that is in a class of drugs called "non-steroidal antiinflammatory drugs." It is an analgesic and antipyretic that is used to treat mild to moderate pain as well as reduce fever and inflammation. Nimesulide an analgesic can be define as "A drug or medicine given to reduce pain without resulting in loss of consciousness. Analgesics are sometimes referred to as painkiller medications and an antipyretic can be defined as "Something that reduces fever Corresponding Author Rahul Pratap Singh anuraza2009@gmail.com or quells it. Nimesulide is available in several forms including tablets, water-soluble powders, suppositories and topical gels (Shahiwal Aliasgar et al., 2002; Amrutiya A et al., 2010). A doctor should be consulted before taking Nimesulide as it has been linked to possible side effects such as nausea, vomiting, diarrhea, pruritis, skin rashes, headaches and dizziness. Some serious side effects when used in newborns are renal failure and hepatic failure. MATERIALS AND METHOD Materials For preparation of nimesulide loaded microspongic gel many standard chemicals are required. Nimesulide was received as a gift sample from Arbro Pharmaceutical Ltd. (New Delhi). Eudragit RS 100 was gifted by Evonik Degussa Pvt. (India). Triethyl citrate was purchased from Chemport Pvt. Ltd. (India). Other materials used in the study (acetone, disodium hydrogen phosphate, polyvinyl alcohol 72000, potassium hydrogen phosphate, sodium carbonate, sodium chloride, sodium hydroxide, hydrochloric acid) were analytical grade.

2 50 Double distilled water was used throughout the study. Ex-vivo studies were performed in accordance with protocols approved by IAEC in Institute of Pharmacy, Bundelkhand University, Jhansi, India (Approval No: BU/PHARM/IAEC/10/021). Methods Preparation of Nimesulide Loaded Microsponges by Quasi-Emulsion Solvent Diffusion (Saboji J K et al., 2011) In this study microsponges were prepared by using quasi emulsion diffusion method by using different drug and polymer ratio (Orlu M et al., 2006). In this method two major chemical phases were used for the preparation of drug loaded microspongic particles (Nikhodchi A et al., 2006). First internal phase nimesulide and eudragit RS 100 was dissolve in 5 ml acetone. In this procedure acetone was an effective solvent for both drug and polymer. Second external phase 60 ml of an aqueous solution containing 0.4% w/v polyvinyl alcohol 72,000 was placed in the reaction vessel. After preparation of both phases, internal phase was gradually poured into external phase. The mixture was stirred at rpm for 3 hour at 40 0 C temperature to remove acetone in free environment from reaction vessel. The formed microsponges were filtered, washed with distilled water, and dried in an air heated oven at 40 0 C for 12 hour and weight determine production yield. Method of Preparation of Nimesulide Loaded Microsponge Gel Accurate weight amount of carbopol 934 was placed in known amount of distilled water. After complete dispersion the carbopol 934 solution was kept in dark for 24 hours for complete swelling. Nimesulide loaded microsponges (containing 10 mg Nimesulide) was dissolved in a specified quantity of suitable solvent. The drug solution was added slowly to the aqueous dispersion of polymer with the help of high speed stirrer taking precaution that air did not entrap. Finally, the remaining ingredients were added to obtain a homogeneous dispersion of gel. The formed gel was then neutralized by sufficient quantity of triethanolamine. Final volume was adjusted by glycerine. Characterization and Evaluation of Nimesulide Loaded Microsponges FTIR Studies FTIR spectrum of Nimesulide, Eudragit RS 100 and Carbopol 934 were measured by the potassium bromide disk using Perkin Elmer Model 1600 FTIR spectrometer (USA). After running the spectra, significant peaks relating to major functional groups were identified and spectra of the subsequent sample of the same compound were compared with the original. Scanning Electron Microscopy The morphology and size of microsponge were observed by scanning electron microscopy. Prepared microsponges were coated with gold-palladium by using sputter coater (Polaron SC-76430) under an argon atmosphere at 180 Ma for 5-7 minutes, after fixing the sample in individual stabs, all samples of microsponges were then randomly by using scanning electron microscope (LIO 430 VP Eindhoven) at different magnification. Drug Encapsulation Efficiency (DEE) Microsponges equivalent to 20 mg of the drug were taken for evaluation. The amount of drug entrapped was estimated dissolving with 10 ml ph 5.8 phosphate buffer solution. The unentrapped drug was separated from the microsponges by subjecting the dispersion to centrifugation in a cooling centrifuge (Remi Equipment s, Mumbai, India) at 20,000 rpm for 4 hours, where upon the particles of microsponges and the supernatant containing free drug were obtained. The solution was filtered and the absorbance was measured by UV spectrophotometer at 300 nm against appropriate blank after suitable dilution. The drug entrapment efficiency in the microspheres was calculated by the following formulas: Drug entrapment efficiency determination Evaluation of Nimesulide Loaded Microsponge Gel Five formulations of microsponges containing nimesulide were characterized by clarity, ph measurement, spreadability and drug content efficiency. Clarity: The clarity of formulation was determined by visual inspection under black and white back ground and it was graded as follow turbid (+), clear (++), transparent (+++). ph: 10 g of gel was accurately weight and dispersed in 10ml of distilled water. The ph of dispersion was measured by using digital ph meter. The ph of Microspongic gel and marketed gel formulations was observed and results were given in Table No. Spreadability: It was determined by wooden block and glass slide apparatus. For the determination of spreadability excess of sample was applied in between two glass slides and was compressed to uniform thickness by placing 1000 g weight for 5 minute. Weight (50 g) was added to pan. The time required to separate the two slides, i.e. the time in which the upper glass slide moves over the lower plates was taken as measure of spreadability.

3 51 Drug content: The Nimesulide gel of 100 mg was dissolved in 10 ml of phosphate buffer ph 5.8. The volumetric flask containing gel solution was shaken for 2 hr on mechanical shaker in order to get complete solubility of drug. This solution was filtered and estimated by UV spectrophotometer. All evaluation data of nimesulide loaded microspongic gel formulation were given in table no.6. EVALUATION OF GEL FORMULATIONS In-vitro drug release studies of nimesulide loaded micropongic gel through dialysis membrane An in-vitro release study (Sevgi IF et al., 2009) was carried out in Franz diffusion cell using treated cellophane membrane in between donor and receiver compartment. The normal surface of the Franz diffusion cells which were used was 1.53 cm 2 and receiver compartment had a capacity of approximately 20 ml. In this drug release studies cellophane membranes were mounted in Franz diffusion cells and the membrane surface dosed with 1gm gels containing Nimesulide loaded microsponge particles or gel. Receptor fluid composed of acetonitrile/phosphate buffer ph 5.8 (1:1) was added to the cell and temperature maintained at 37 C ± 1 0 C because of the exceedingly low solubility of Nimesulide in normal saline, a acetonitrile/phosphate buffer ph (5.8) mixture was selected as receptor fluid to provide adequate sink conditions after preliminary experiments showed no interactions of this mixture with either the membrane or the mixtures placed on the donor side.. The dissolution medium was stirred at rpm speed using teflon coated magnetic bead. Aliquots, each of 2 ml volume were withdrawn periodically at predetermined time interval of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 24 hour and replaced by an equal volume of the receptor medium. The aliquots were suitably diluted with the receptor medium and analyzed by UV spectrophotometer at nm using phosphate acetonitrile/buffer (ph 5.8) as blank. Absorbance of these samples was measured at λ max nm using HPLC. Cumulative percentage drug release was calculated using an equation obtained from the standard curve. The drug release data were observed and givenin table no 7, 8 and figure no. 5. The release studies were performed in triplicate. IN-VITRO EVALUATION APPLICATION OF DIFFERENT KINETIC MODELS FOR IN-VITRO DRUG RELEASE All animals were housed at room temperature 30 0 C (± 1 0 C). All animals were randomly assigned to different groups and a period of one week allowed for adaptation commencement of each experiment. The rats were injected subcutaneously 0.1 ml of 1% (w/v) of carrageenan in to the planter region of the each hind paw and the paw volume was measured after 1hr, 2 hr, 3 hr, 6 hr, 12 hr, and 24 hr using mercury plethysmometer. The right paw served as a reference non inflamed paw for comparison. The percentage difference between right and left paw volumes was taken as percent edema produced. The percent edema produced with test samples were subtracted from percent edema produced in control group to obtain percent edema inhibition by respective groups. Percent inhibition of edema is directly proportional to the anti-inflammatory activity. The anti-inflammatory effect of Nimesulide loaded microspongic gel were found and reported in table no. 8 and figure no. 10. Stability Studies The optimized formulation of nimesulide loaded microspongic gel was subjected for stability studies. After measurement of initial percentage entrapment of the drug in the various formulations, the three batches of the same formulation were stored in sealed aluminium tube (one each) at 5 ± 1 0 C, room temperature (30 ± 1 0 C) and 40 ± 1 0 C for a period of at least 45 days. After every 7 days, percentage entrapment of drug was determined in the formulation to know the amount of drug leaked out. The percentage drug lost was calculated taking the initial entrapment of drug as 100%. The percentage drug entrapment was measured and results were given in table no. 9 and figure no. 11. RESULTS AND DISCUSSIONS In quasi-emulsion solvent diffusion method, the formation of the microsponges could be described in the following processes: the formation of quasi-emulsion droplets, the diffusion of the acetone and the solidification of the droplets (Nacht S and Kantz M 1992). The rapid diffusion of acetone (good solvent for the polymer and drug) into the aqueous medium containing PVA might reduce the solubility of the polymer in the droplets, since the polymer was insoluble in water (Nokhodchi et al., 2005). The instant mixing of the acetone and water at the interface of the droplets induced precipitation of the polymer, thus forming a shell enclosing the acetone and the dissolved drug. Counter diffusions of acetone and water through the shell promoted further crystallization of the drug in the droplets from the surface inwards. The finely dispersed droplets of the polymer solution of the drug were solidified in the aqueous phase via diffusion of the solvent. Then it was filtered to separate microsponges, and dried by hot air oven at 50 0 C for 24 hours. Evaluation drug loaded micrsponsic microparticles The drug polymer compatibility was characterized by means of FTIR spectroscopy. The compatibility was checked by making physical mixture of drug and polymer (1:1) and then the FTIR analysis of

4 52 the mixture was done. There no difference in IR signals of drug alone and drug with polymers which proved the absence of any possible interaction between the drugs and polymers. The FTIR observed scan image were showing drug interaction in figure no. 2. SEM images showed that the microparticles were porous in nature and spherical in shape. The pores were induced by the diffusion of the solvent from surface of the microparticles. A SEM of microsponge (NMRS 7) revealed that the structure of microsponge consists of void spaces (pores), clearly visible from outside at high magnification. The appearance of the particles was such that they were termed microsponges. SEM scan images were showing in figure no. 3 and 4. Drug entrapment efficiency (DEE) is important parameter to be defined to really evaluate the delivery potentiality of the system. For this reason, the DEE of Nimesulide within the microsponge formulations was evaluated. At all ratios of drug:polymer employed, the mean amount of drug entrapped in the prepared microsponges was lower than the theoretical value, since the drug loading efficiency did not reach 100%. The drug entrapment efficiency (DEE) of the microsponges was estimated by using HPLC. The DEE of microsponges was in the range ± 2.16 % to ± 0.36 % being highest for NMRS 7 and lowest for NMRS 1. The observed drug contents efficiency of prepared formulations was given in table no. 5 and figure no. 5. Evaluation of drug loaded micropongic gels Clarity: NMRS Carbopol 934 gels were found to be sparkling and transparent and marketed gel was white. All gels were viscous free from presence of particles. The clarity was observed by visualisation method. ph: The ph value of all developed formulation of NMRS Carbopol 934 gels (NMRS 5-NMRS 13) were in the range of ph and marketed gels were ph 6.5. Spreadability: The value of spreadability indicates the gel is easily spreadable by small amount of shear. The spreadability of NMRS gels in the range g.cm/sec whereas marketed gel spreadability was found to be g.cm/sec. Drug content: The percentage drug content of all prepared gel formulations were found to be in the range of %, whereas the drug content of marketed gel was %. The percentage drug content of all formulations was found satisfactory. Hence methods adapted for gels formulations were found suitable. In-Vitro Drug Release Studies In this study were prepared various Nimesulide loaded microspongic gel formulations. The In-vitro drug release studies were conducted on Franz diffusion cell dissolution apparatus. The drug releases from microspongic gel (NMRS) formulations were carried out in a mixture of acetonitrile:phosphate buffer ph 5.8 and the temperature was maintained at 37 ± 2 0 C (Amrutiya A et al., 2010). Drug release from the NMRS gels was slow (NMRS 5 to NMRS 7) and depends on the particle size and drug encapsulation efficiency of microsponge formulations. The release of profiles obtained for the microspongic gel formulations was presented in the table no. 7. The profiles showed a bi-phasic drug release mechanism of microspongic formulations. In the second hour drug release was 8.27 ± 0.22 %, ± 0.02 %, 6.06 ± 0.10 %, 3.40 ± 0.17 % and ± 0.42 % from NMRS 5, NMRS 7, NMRS 9, NMRS11 and NMRS13 gels respectively. The mechanism for the burst release can be attributed to the drug loaded on the microsponges or imperfect entrapment of drug. The overall cumulative % drug release from NMRS 5, NMRS 7, NMRS 9, NMRS11 and NMRS13 gels were found to be ± 0.26 %, ± 0.19 %, ± 0.16 %, ± 1.02 and ± 0.84 at the end of 24 hour. The in-vitro release of Nimesulide from NMRS gel made of Eudragit RS100 polymers depended on the polymer concentration used. This indicates that the drug release rate increases with increasing amount of the drug (NMRS 5 to NMRS 13). This can be explained by a decreased amount of polymer present close to the surface and also by the fact that the amount of uncoated drug increases with higher drug concentration. It was also observed that the release rate of drug from Eudragit RS 100 also increased. These observations could be attributed to the fact that Eudragit RS 100 microsponges have thin polymeric surface at higher drug: polymer ratio. The thin polymeric barrier slows the entry of surrounding dissolution medium in to the microsponges and hence high quantity of drug leaches out from the polymer matrices of the microsponges exhibiting high release within time of 24 hours. The results of drug permeation coefficient and flux study through cellophane membrane from microspongic gel formulations were given in the Table No The drug permeation coefficient and flux of Nimesulide from microspongic gel formulations NMRS 1, NMRS 3, NMRS 5, NMRS 7, NMRS 9, NMRS 11 and NMRS 13 was ± 0.00, ± 0.01, ± 0.00, ± 0.02 and ± 0.01, and ± 0.50, ± 0.16, ± 1.21, ± 1.60 and ± 0.24 (µg/cm 2 /hr) respectively at various drug: polymer ratio. Application of different kinetic models for in-vitro drug release To find out the kinetics and mechanism of drug released from all the formulations of Nimesulide bearing microspongic gel, the data were treated according to Zero order, First order, Higuchi square root law and Korsmeyer s and Peppas kinetic. The results were clearly indicated in the table no. 8 and figure no. 6, 7, 8 and 9. This suggested that the release of Nimesulide from

5 53 NMRS gel exhibits diffusion characteristics, closely following Higuchi model and is highly correlated with first order and Korsmeyer s and Peppas release kinetics. Ex-Vivo studies The anti-inflammatory activity of Nimesulide loaded microspongic gel (NMRS) was studies by using carrageenan induced rat paw edema method. Nimesulide loaded microspongic gel was gave a potent antiinflammatory effect, when tested in rat paw edema model. It was evaluated at 1 g (1 % w/w) dose topically. It showed a slight response at +3 hour. But after + 6 hour they showed significant effect in inhibition of paw edema. Nimesulide loaded microspongic formulation was gave better results in comparison to marketed gel (Nise Gel). The observed data were given in the table no 8 and Figure No. 10. The data obtained from each experiment were subjected to statistical analysis by Student t-test and one-way analysis of variance (ANOVA) using Graph Pad Instat software. P < 0.05 was considered to be indicative of significance. Stability studies Nimesulide loaded microsponges (NMRS 7) stored at 5 ± 1 0 C, room temperature (30 ± 1 0 C) and 40 ± 1 0 C, 75% (RH) were subjected to stability studies. Optimal storage condition of the formulation assessed to analysing the residual drug content after the time intervals 0, 7, 14, 28, 35 and 45 days. The present residual content was plotted against time (t). The stability studies were applied on formulation NMRS 7 because of their good encapsulation efficiency. The Nimesulide loaded microsponges were stored in glass bottles at 4 ± 1 0 C, 30 ± 1 0 C (room temperature), and 40 ± 1 0 C, temperature for one month. The samples were withdrawn after 7, 14, 28, 35 and 45 days and sample were analyzed for drug content. The percentage drug retained at 4 ± 1 0 C for 45 days was found to be 100 ± 0.00, ± 0.18, ± 0.10, ± 0.25, ± 0.06, ± 0.05 and ± 0.37 for optimized formulation NMRS 7. The percentage drug retained at room temperature (30 ± 1 0 C) for 45 days was found to be 100 ± 0.00, ± 0.24, ± 0.12, ± 0.07, ± 0.13, ± 0.19 and ± 0.24 for optimized formulation NMRS 7. The percentage drug content retained at (40 ± 1 0 C) for 45 days was found to be 100 ± 0.00, ± 0.37, ± 0.01, ± 0.05, ± 0.17, ± 0.09 and ± 0.15for optimized formulation NMRS 7. The decrease in drug content was found but it is in prescribed limits as per degradation phenomena. Thus, it was found that the optimized formulation NMRS 7 was stable under storage conditions. The observed date was presented in the table no. 11. Figure 1. Preparation of Nimesulide loaded Microspongic particles

6 54 Figure 2. FTIR spectrum of mixture Nimesulide, Eudragit RS 100 and Carbopol 934 Figure 3. Scanning electron micrograph of Nimesulide loaded Microsponges at 100 X Magnification power

7 55 Figure 4. Scanning electron micrograph of Nimesulide loaded Microsponges at 712 X Magnification Power Figure 5. % Drug entrapment efficiency of various Microspongic formulations Evaluation of Nimesulide Loaded Microsponge Gel Figure 6. Zero order kinetic treatment of various Microspongic gel formulations

8 56 Figure 7. First order kinetic treatment of various Microspongic gel formulations Figure 8. Higuchi s square root kinetic treatment of various Microsponge gel formulations Figure 9. Korsmeyer s and Peppas kinetic treatment of various Microspongic gel formulations

9 57 Figure 10. % Edema inhibition in rat paw after gel application Figure 11. Effect of aging on drug content of optimized batch at 5 0 C, Room temperature (30 ± 1 0 C) and 40 0 C, 75 RH Table 1. Formulation Chart of Nimesulide loaded Microspongic Particles S. No. Formulation Code Drug:Polymer Ratio Acetone (ml) TEC (ml) PVA (%w/v) Water (ml) 1 NMRS 1 1: NMRS 3 3: NMRS 5 5: NMRS 7 7: NMRS 9 9: NMRS 11 11: NMRS 13 13: Table 2. Formulation of Nimesulide Loaded Microspongic Gels (NMRS Gel) S. No. Ingredients Formulations % w/w 1 Nimesulide (free or loaded, equivalent to) Carbopol Menthol Methyl paraben Propyl paraben Sodium metabisulphite Disodium edentate Acetone Q.S. 9 Purified water Q.S.

10 58 Table 3. Interpretation of FTIR Spectrum of mixture of Nimesulide, Eudragit RS100 and Carbopol 934 S. No. Frequency (cm -1 ) Assignments Classes C-H Stretching Alkynes Ar O-H, H Bonded Phenols N-O Assym. Stretching, Ar-C-C Stretching Misc. Aromatic S=O Sulphate Ester, Ar-C-C Stretching Misc. Aromatic C-O Stretching Ethers Carboxylic Acid C-O Stretching, nc-n Stretching Ethers Amines Table 4. SEM report of optimized Microspongic formulation NMRS 7 S. No. Formulation Code Drug: Polymer Ratio MagnificationPower (X) Photo No. Particle Size (μm) 1 NMRS 7 7: NMRS 7 7: Table 5. % Drug entrapment efficiency (DEE) of Microspongic formulations S. No. Formulation Code Drug: Polymer Ratio Drug Entrapment Efficiency (% ±) 1 NMRS 1 1: ± NMRS 3 3: ± NMRS 5 5: ± NMRS 7 7: ± NMRS 9 9: ± NMRS 11 11: ± NMRS 13 13: ± 1.11 Result have been expressed as Mean ± S. D. (n=3) Table 6. Clarity, ph, Homogeneity and Spreadability determination of various gel formulations S. No. Form. Code Clarity ph Spreadability Drug Content (%) 1 NMRS NMRS NMRS NMRS NMRS Marketed Gel Table 7. Comparative cumulative drug release from various Microspongic gel Formulations Time in hour Cumulative % Drug Release NMRS 5 NMRS 7 NMRS 9 NMRS 11 NMRS ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± 0.84 Result have been expressed as Mean ± S. D. (n=3)

11 59 Table 8. Zero, First order kinetic, Higuchi s square root kinetic and Korsmeyer s and Peppas kinetic treatment of release data of various Nimesulide loaded Microspongic Gels Formulation code Zero order kinetic Correlation First order kinetic Correlation Higuchi s square root kinetic Correlation Korsmeyer s and Peppas kinetic Correlationcoefficient(R 2 ) coefficient (R 2 ) coefficient (R 2 ) coefficient (R 2 ) NMRS NMRS NMRS NMRS NMRS Table 9. Ex-Vivo Anti-inflammatory effects of NMRS 7 and marketed gel (Nise Gel) in carrageenan induced rat paw edema Group Formulation No. of animal in Mean Wt of Time in % Edema % Edema each group rat ± SD (g) hour ± SD inhibition ± ± ± ± 0.4 I Control (Plain ± ± ±25.5 Nimesulide Gel) ± ± ± ± ± ± 0.2 II NMRS 7 Gel 5 205±30.5 III Conventional Gel ±50.5 Result have been expressed as Mean ± S. D. (n=3) ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± 0.8 Table 10. Stability data of Nimesulide loaded Microsponges NMRS 7 S. No. Sampling Interval Drug Entrapment (%) (Days) 5 ± 1 0 C Room temperature (30 ± 1 0 C) 40 ± 1 0 C, 75 % RH 1 0 th ± ± ± th ± ± ± th ± ± ± th ± ± ± th ± ± ± th ± ± ± th ± ± ± 0.15 Result have been expressed as Mean ± S. D. (n=3) CONCLUSION Nimesulide loaded microspongic gels been developed to provide better once a day sustained release medication for topical delivery in inflammation diseases. Nimesulide loaded sustained microspongic gel was prepared successfully using novel polymeric combinations of eudragit RS 100 was used in microsponge formulation and Carbopol 934 was used gel formulation. Nimesulide loaded microspongic gel clearly increase drug deposition time on the skin up to 24 hour or within the epidermis while minimizing its penetration through the dermis and therefore in to the body. The

12 60 release pattern of the NMRS gel followed the Korsmeyer s and Peppas kinetic indicating Fickian diffusion. Topical administration of Nimesulide will reduced gastric side effect and improve the therapeutic drug efficacy. These finding are very encouraging and confirm that Microsponges are very promising carrier for the topical administration due to the enhanced delivery of the drugs through the skin thus prompting various opportunity for development of suitable therapeutic strategies through topical route. ACKNOWLEDGEMENT The authors are thankful to Institute of Pharmacy, Jhansi for providing modern facilitated laboratory and Pharmaceutical Ltd., New Delhi for providing the sample of Nimesulide. REFERENCES Amrutiya A, Bajaj A, Madan M. Development of Microsponges for Topical Delivery of Mupirocin. AAPS Pharm Sci Tech. 2010; 10(2): Comoglu T, Gonul N, Baykara T. Preparation and In-Vitro evaluation of Modified Release Ketoprofen Microsponges. Farmaco. 2003; 58(2): Comoglu T, Gonul N, Baykara T. The Effect of pressure, Direct Compression Tabletting of Microsponges. Int J Pharm. 2002; 241: Kawashiama YN, Toshiyuki TH, Hino TI. Control of Prolonged Drug Release and Compression Properties of Ibuprofen Microsponges with Acrylic Polymer, Eudragit RS, by Changing their Intraparticle Porosity. Chem and Pharm Bull. 1992; 40(1): Nacht S and Kantz M. The Microsponge: A Novel Topical Programmable Delivery system. Topical Drug Delivery Systems. 1992; 42: Nokhodchi A, Jelvehgari M, Siahi M R, Dasmalchi S. The Effect of Formulation Type on the Release of Benzoyl Peroxide from Microsponges. Iranian J Pharm Sciences. 2005; 1(3): Nokhodchi A, Jelvehgari M, Siahi M. Factors affecting the morphology of benzoyl peroxide microsponges. J. Micron. 2007; 3: Orlu M, Cevher E, Araman A. Design and Evaluation of Colon Specific Drug Delivery System Conataining Flurbiprofen Microsponges. Int J Pharm. 2006; 318: Saboji JK, Manvi FB, Gada AP, Patel BD. Formulation and Evaluation of Ketoconazole Microsponge Gel by Quasi Emulsion Solvent Diffusion. J Cell Tissue Res. 2011; 11(1): Sevgi. IF, Yurdasiper A, Kaynarsory B, Turunc E. Studies on Mefenamic Acid Microparticles: In-Vitro Release and In Situ Studies in Rats. AAPS Pharm Sci Tech. 2009; 10(1): 1-5.