Formulation and Evaluation of Mouth Dissolving Tablets of Piroxicam

Singh et al: Formulation and Evaluation of Mouth Dissolving Tablets of Piroxicam 2941 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 8 Issue 3 July September 2015 Research Paper MS ID: IJPSN-1-12-15-SINGH Formulation and Evaluation of Mouth Dissolving Tablets of Piroxicam Sudarshan Singh*, S.S. Shyale and G. Bhosale Department of Pharmaceutics, HSBPVT s, College of Pharmacy, Kashti, Maharastra, India. Received January 12, 2015; accepted May 13, 2015 ABSTRACT Piroxicam, a non-steroidal anti-inflammatory agent, is widely used in rheumatoid arthritis, osteoarthritis, musculoskeletal disorders, dysmenorrhoeal and post-operative pain. It has poor bioavailability due to its inherent properties. The objective of present study is to enhance water solubility of Piroxicam by solid dispersion technique and to develop novel method of preparing compressed tablets for Piroxicam with high porosity which dissolves rapidly in mouth, using camphor as sublimating agent and super disintegrants such as Crosscarmellose sodium and sodium starch glycollate. The tablets were evaluated for hardness, thickness, friability, weight variation, wetting time, disintegration time, drug content and in vitro drug KEYWORDS: Piroxicam; β-cyclodextrin; Crosscarmellose Sodium; Sodium Starch Glycollate. release. Optimized formulation was evaluated for stability according to ICH guideline. All tablets had hardness in range of 2.8-3.1 kg/cm2 and friability of all formulations was less than 1.0%. Weight variation and drug content were within USP limits. A stability study for optimized F6 formulation 40 C / 75 % RH for 30 days showed little change in drug content. Therefore, it is concluded that enhance solubility and increased levels of the super disintegrants Cross carmellose sodium and sodium starch glycollate increases the rate of Piroxicam release. Camphor decreases disintegration time of tablets and create high porosity which dissolve rapidly in mouth and could be industrially feasible. Introduction Many patients, especially elderly find it difficult in swallowing tablets, capsules, fluids and thus do not comply with prescription, which results in high incidence of non-compliance oriented research has resulted in bringing out many safer and newer drug delivery systems. Rapidly disintegrating/dissolving tablet is one of such example, for the reason of rapid disintegration or even with saliva. Significance of this drug delivery system includes administration without water, accuracy of dosage, ease of portability, alternative to liquid dosage forms, ideal for paediatric and geriatric patients and rapid onset of action (Prajapati and Ratnakar, 2009). Piroxicam is chemically, 4-hydroxyl-2-methyl-N-2- pyridinyl-2h-1,2-benzothiazine 3-carboxamide-1,1-dioxide. It is a selective cyclooxygenase-2 inhibitor used in the treatment of rheumatoid arthritis, osteoarthritis and other joint diseases. The poor aqueous solubility of the drug gives rise to difficulties in the formulation rates. Therefore, in the present study, we made an attempt to increase the water solubility of Piroxicam by solid dispersion techniques by forming inclusion complex of drug β-cyclodextrin by kneading method and prepare mouth dissolving tablets of Piroxicam in the oral cavity with an emphasis on enhanced dissolution rate for improved patient compliance (Widjaja andsetyawan, 2013). Materials and Methods Piroxicam was received as a gift sample from Matrix PharmaPvt. Ltd., Aurangabad Maharashtra. CrosscarmelloseSodium(CCS) and Sodium Starch Glycollate (SSG) was received as a gift sample from Signet Chemical Co Ltd, BandraKurla Complex, Mumbai β- Cyclodextrin (β-cd) was procurred from Yash scientific pune and other materials used were of analytical grade and procured from commercial sources. Methods Solubility enhancement by using β-cyclodextrin: Inclusion complexes were prepared by kneading method. Piroxicam with β-cyclodextrin in different molar ratios (1:1, 1:1.5, 1:2) was used. β-cyclodextrin was added to the mortar, small quantity of distilled water was added while triturating to obtain a homogenous paste. The drug was slowly added to the paste and mixture triturated for one hour. During the process, the water content of the paste was empirically adjusted to maintain the consistency of the paste. The paste was dried at 40 o C for 24 hr, pulverized by passing through sieve no. 85 and stored in a desiccators till further use (Radha et al., 2010). Drugexcipients compatibility studies: The FT-IR spectrum of Piroxicam, physical mixture of Piroxicam with sodium starch glycollate and Crosscarmellose sodium were analysed to verify the compatibility between the pure drug and polymers using FT-IR (Make Varian 2941

2942 Int J Pharm Sci Nanotech Vol 8; Issue 3 July September 2015 Cary, Model-510) by KBr disc method. The procedure consisted of dispersing a sample (drug alone or mixture of drug and polymers) in KBr and compressing into discs by applying a pressure of 5 tons for 5 min in a hydraulic press. The pellet was placed in the light path and the spectrum was obtained, to identify functional groups and bands of drug or its mixture (Patrick and Sinko, 2009).TheDSC thermogram of the Piroxicam and physical mixtures of Piroxicam with sodium starch glycollate and Crosscarmellose sodium were obtained using Shimadzu DSC-60 (Shimadzu Limited Japan) by heating at a scanning rate of 10 C/min over a temperature range 50 C - 300 C under nitrogen environment(patrick and Sinko, 2009). DSC thermogram of pure Piroxicam and formulation were obtained to verify chemical interaction between drug and excipients. Preparation of Mouth dissolving tablets: The mouth dissolving tablets were prepared by direct compression method. The composition of mouth dissolving tablets is presented in Table 1. Drug β-cd complex and excipients were accurately weighed and mixed. Tablets were compressed using 6 mm flat punch Tablet press 10 station compression machine (Cemach R and D) (Bhowmik et al., 2009). Hardness of the tablets between was kept between 3-3.5 Kg/cm 2. Tablet weight was maintained at 150 mg. All the product and process variables were kept as practically constant. TABLE 1 Composition of prepared mouth dissolving tablets. Ingredients (in mg) Drug β-cd (eq. to 20mg ) Batch Codes F1 F2 F3 F4 F5 F6 F7 F8 F9 68.5 68.5 68.5 68.5 68.5 68.5 68.5 68.5 68.5 CCS 27 27 27 18 22.5 27 - - - SSG - - - - - - 18 22.5 27 Sucrose 54.5 51.5 44 50 45.5 41 50 45.5 41 Camphor - - 10.5 10.5 10.5 10.5 10.5 10.5 10.5 Aerosil - 3-3 3 3 3 3 3 Total (mg) 150 150 150 150 150 150 150 150 150 Pre-compression evaluation parameter: The powder bed was evaluated for the blend property such as Bulk density, Tapped density, Carr s index, Hausner s ratio and Angle of repose (Lachman and Liberman, 2009). Evaluation of mouth dissolving tablets: Mouth dissolving tablets of Piroxicam were evaluated for their post-compression parameters such as weight variation, hardness, thickness, friability, uniformity of weight and drug content uniformity (Bhowmik et al., 2009; Lachman and Liberman, 2009). Disintegration test: Disintegration of rapidly disintergrating oral tablets is achieved in the mouth owing to the action of saliva; however amount of saliva in the mouth is limited. A modified method was used to determine disintegration time of the tablets. A cylindrical vessel was used in which 10 mesh a screen was placed in such a way that only 2 ml of disintegrating medium would be placed below the sieve. To determine disintegration time, 6 ml of phosphate buffer (ph 6.8), was placed inside the vessel in such a way that 4 ml of the media was below the sieve and 2 ml above the sieve. Tablet was placed on the sieve and the whole assembly was then placed on a shaker. The time at which all the particles pass through the sieve was taken as a disintegration time of the tablet (Ashishet al., 2011). Wetting time: A Petri dish containing 6 ml of 6.8 phosphate buffer was used. Tissue paper folded twice was kept in the dish and a tablet was placed on it. A small quantity of Amaranth red colour was added on the upper surface of the tablet. Time required for the upper surface of the tablet to become red was noted as the wetting time of the tablet (Ashish et al., 2011). In vitro drug release profile of piroxicam: In-vitro release from rapidly disintegrating tablets of Piroxicam was determined using USP dissolution testing apparatus II (paddle method). The dissolution test was performed using 900 ml of 0.1 N HCl, ph 1.2 at 37 ± 0.5 C and 50 rpm (Ashish et al., 2011) specified amount of sample (5 ml) of the solution was withdrawn from the dissolution apparatus at different time intervals and the samples were replaced with fresh dissolution medium. Later the withdrawn sample was diluted to suitably with 0.1 N HCl, ph 1.2. Absorbance of these solutions was measured at 334 nm using a UV Visible double beam spectrophotometer (Jasco v-630). Cumulative percentage drug release was calculated using an equation obtained from a standard curve. Dissolution profile comparisons (using a similarity factor): A simple model independent approach uses a difference factor (f1) and a similarity factor (f2) to compare dissolution profiles. The difference factor (f1) calculates the percent (%) difference between the two curves at each point and is a measurement to the relative error between the two curves. f1= {[Σn=1 n Rt Tt ]/ [Σt=1 n Rt ]} 100 Where n is the number of time point, Rt is the dissolution value of the reference batch at time t, and Tt is the dissolution value of the test batch at time t. The similarity factor (f2) is the logarithmic reciprocal square root transformation of the sum of squared error and is a measurement of the similarity in the percent (%) dissolution between the two curves. f2 = 50 log {[1+ ( 1/n) Σt=1n ( Rt Tt )2 ]-0.5 100} For the curves to be considered similar, f1 values should be close to 0 and f2 values should be close to 100. Generally, f1 values up to (0-15) and f2 values greater than 50 (50-100) ensures sameness or equivalence of the two curves and thus, of the performance of the test and reference products (Singhet al., 2009). The comparative dissolution was performed using Piroxicam 20mg. Statistical analysis: Results obtained for above disintegration time, wetting time and in vitro dissolution studies measurement are expressed as mean SEM (Standard Error Mean) and subjected to one-way analysis of variance (ANOVA) with P < 0.05 were considered to be statistically significant (Subrahmanyam, 2000).

Singh et al: Formulation and Evaluation of Mouth Dissolving Tablets of Piroxicam 2943 Stability study: To assess the drug and formulation stability, stability studies was performed according to ICH guideline. Optimized mouth dissolving tablets were sealed in aluminium packing and kept in humidity chamber maintained at 40 C and 75% RH for 90 days. Samples were analyzed for the drug content, surface ph, in vitro drug release study and other physicochemical propertiesat regular intervals(jens and Rhodes, 2009). Results and Discussion Solubility enhancement of Piroxicam using β-cyclodextrin: A complex of Piroxicam and β-cyclodextrin in different molar ratios (1:1, 1:1.5, and 1:2) were prepared. The solubility of Piroxicam: β-cd complex was studied. The solubility of 1:1 ratio is greater as compared to pure drug, 1:1.5 and 1:2 ratios. Results are presented in Fig. 1. Fig. 1. Solubility of piroxicam in different solvents at λmax 334 nm. Drugexcipients compatibility studies by FTIR: The result of FTIR spectra for pure drug is presented in Figure 2, the characteristic peaks of Piroxicam N-H stretch at 3340.378 cm 1, C-H stretch at 2934.757 cm 1, C=C stretch at 1578.073 cm 1 and C-N stretch at 1279.784 cm 1, OH bend at 938.820 were not affected. Based on the findings of physical constants and spectrophoto-metrically analysis, the sample of Piroxicam was considered to be authentic. The result of FTIR spectra for optimized batch is presented in Figure 3, the characteristic peaks of Piroxicam N-H stretch at 3339.028 cm 1, C-H stretch at 2933.879 cm 1, C=C stretch at 1529.315 cm 1 and C-N stretch at 1279.784 cm 1, OH bend at 939.582 were not affected. It was found that all excipients were compatible with Piroxicam. Drug excipients compatibility studies by DSC: DSC analysis was performed on Shimadzu DSC-60(Shimadzu Limited Japan). DSC thermogram of pure Piroxicam and mixture of drug with CCS and sucrose are presented in Figure 4 and 5 The DSC thermogram of Piroxicam showed an endothermic peak at 203.33 C corresponding to its melting point. Melting point obtained experimental values is nearer to this value. The thermogram of drug with CCS and sucrose showed an endothermic peak at 202.41 ºC which is similar to the melting point of the drug. Thermogram indicated that, the drug is compatible with the excipients CCS or sucrose or its mixture. Pre-compression evaluation: Bulk density and Tapped density were found in acceptable limit which indicated that the packing properties required during compression are adequate in all formulations. Carr s index indicated a good compressibility. Hausner s ratio and angle of repose were found in acceptable limit which implies good flow properties. The results were tabulated in Table 2. Evaluation of Mouth dissolving tablets: Tablets of formulation batches were evaluated for thickness, diameter, average weight, hardness, friability and drug contentsresults were tabulated in Table 3. The tablets mean thickness and diameters of all formulation was found to be in the range of 3.7 to 3.9 mm and 6.01 to 6.05 mm respectively. All batches pass weight variation test and found to be within range. The hardness is within the range of 2.8 to 3.1 kg/cm 2, it indicates that tablet have good mechanical strength.the tablets mean diameters and thickness of formulations were found to be in the range of 6.01 to 6.05 mm and 3.7 to 3.9 mm respectively. Friability was found to in the range of 0.45 to 0.89 %. The friability was less than 1% in all the formulations ensuring that the tablet were mechanically stable.the drug content were found to be between 98.21 % ± 1.01 to 100.83 % ± 1.05, indicates uniformity of blending and consistency. Fig. 2. FTIR spectrum of the piroxicam.

2944 Int J Pharm Sci Nanotech Vol 8; Issue 3 July September 2015 Fig. 3. FTIR spectrum of optimized batch F6. DSC mw Thermal Analysis Result 0.00-10.00 Fig. 4. DSC Thermogram of piroxicam pure drug. -20.00-30.00 203.33 C 50.00 100.00 150.00 200.00 250.00 Temp [C] TABLE 2 Evaluation of pre-compression parameters of tablet blends. Batch code Bulk density g/ml ± SD Tapped density g/ml ± SD Carr s index% Hausner s ratio Angle of repose ± SD F1 0.5882 0.01 0.7143 0.03 17.64 1.2143 30.85 0.39 F2 0.5555 0.03 0.7143 0.01 22.22 1.2857 26.08 0.58 F3 0.5263 0.02 0.6666 0.03 21.05 1.2666 28.74 0.65 F4 0.5263 0.03 0.6666 0.01 21.05 1.2666 28.36 0.61 F5 0.5555 0.04 0.7143 0.01 22.22 1.2857 26.21 0.54 F6 0.4761 0.01 0.5882 0.03 19.04 1.2353 25.96 0.85 F7 0.5263 0.02 0.6250 0.01 15.78 1.1875 29.86 0.20 F8 0.5555 0.01 0.7143 0.04 22.22 1.2857 20.82 0.83 F9 0.4761 0.03 0.5555 0.02 14.29 1.167 29.96 0.39 Note: Values are mean of three observation (n = 3) and Values in parenthesis are Standard Deviation (± SD) TABLE 3 Evaluation of physical properties of tablets. Batch Code Thickness Diameter Average weight of Tablet(mg) ± SD Hardness (kg/cm 2 ) ± SD Friability ± SD % Drug Contents ± SD % F1 3.8 0.08 6.050 0.01 141.07 1.00 2.86 0.04 0.45 0.02 100.83 1.05 F2 3.9 0.08 6.020 0.04 140.67 1.89 2.83 0.09 0.52 0.03 99.43 1.05 F3 3.8 0.08 6.027 0.02 141.03 0.86 2.86 0.04 0.75 0.01 100.38 0.84 F4 3.83 0.09 6.037 0.02 145.03 1.29 3.1 0.08 0.74 0.02 99.49 1.11 Table 3 Contd...

Singh et al: Formulation and Evaluation of Mouth Dissolving Tablets of Piroxicam 2945 Batch Code Thickness Diameter Average weight of Tablet(mg) ± SD Hardness (kg/cm 2 ) ± SD Friability ± SD % Drug Contents ± SD % F5 3.86 0.04 6.010 0.03 145.80 1.44 2.93 0.04 0.69 0.02 99.76 0.92 F6 3.76 0.04 6.020 0.02 141.57 2.10 2.96 0.04 0.73 0.01 99.48 1.07 F7 3.93 0.04 6.010 0.03 142.90 2.0 2.96 0.12 0.89 0.02 99.68 1.15 F8 3.93 0.04 6.033 0.02 141.0 2.26 3.06 0.04 0.78 0.03 98.21 1.01 F9 3.73 0.04 6.027 0.02 140.93 2.20 2.93 0.04 0.89 0.02 99.23 1.05 Note: Values are mean of three observation (n = 3) and Values in parenthesis are Standard Deviation (± SD) Disintegration time: The result of disintegration time is presented in Table 4. A modified method was used to evaluate the in vitro disintegration time because the disintegration rate obtained from conventional test does not appear to reflect the disintegration rate in humans. All batches pass the criteria for disintegration time. It was obtained that formulation batches had a disintegration time in the range of 34.66 1.05 to 102.66 ± 1.60 seconds. Formulations containing Crosscarmellose disintegrated faster than formulations containing sodium starch glycollate. Statistically the data was analysed by one way ANOVA at a P < 0.05. It was found that the data at any point of time are significant at P < 0.05. TABLE 4 Evaluation of various parameters of tablets (n = 3). Batch Code Disintegration time (s) ± SD Wetting Time (s) ± SD F1 58.33 1.655 51.66 1.655 F2 58.33 1.186 51 1.247 F3 37.66 1.186 32.66 0.981 F4 84.66 2.126 75.30 1.089 F5 53.33 1.186 45.66 1.655 F6 34.66 1.905 30.33 0.720 F7 102.66 1.186 89.33 1.785 F8 72.66 1.186 65.00 1.414 F9 55.66 1.440 46.33 0.981 Note: Values are mean of three observation (n = 3) and Values in parenthesis are Standard Deviation (± SD) Wetting time: The result of wetting time is presented in table 4. The dissolution process of a tablet depends on the wetting followed by disintegration of the tablet. The measurement of wetting time may be used as confirmatory test for evaluation of the mouth dissolving tablets. Mean wetting time was found to be in the range of 30.33 0.80 to 89.33 1.16 seconds, presented in Figure 5. Statistically the data was analysed by one way ANOVA at a P < 0.05. It was found that the data at any point of time are significant at P < 0.05. In vitro drug release studies: The result of in vitro drug release study is presented in Figure 6. The comparative study of dissolution profile of batch F1 to F3 shows that in absence of aerosil does not affect on dissolution, disintegration and wetting time. Further in F2 absence of camphor affect on dissolution and increases disintegration and wetting time of tablets. In batch F1, absence of both aerosil and camphor affected the dissolution, disintegration and wetting time. The drug release was found to be 95.26 %, 95.07 %, 99.17 % respectively for batch F1, F2 and F3 within 15 min. The comparative study of dissolution profile of batch F4 to F6 shows that when increase concentration of superdisintegrants Crosscarmellose sodium, percentage drug release was also increased. The drug release was found to be 92.84 %, 95.85 % and 99.57 % respectively for batch F4, F5 and F6 within 15 min. The comparative study of dissolution profile of batch F7 to F9 shows that when increase concentration of superdisintegrants, sodium starch glycollate. The percentage drug release was also increased. The drug release was found to be 91.36 %, 98.51 % and 99.32 % respectively for batch F7, F8 and F9 within 15. Statistically the data was analyzed by one way ANOVA at a P < 0.05. It was found that the data at any point of time are significant at P < 0.05. Fig. 6. Comparative dissolution profile of batches F1 to F9. Dissolution profile Comparisons (Similarity Factor): The dissolution comparisons by model independent approach using a similarity factor f1 was found to be 8.24 and f2 found 54.26 (Figure 8). The comparative study of dissolution profile shows that optimized F6 batch shows better drug release than the marketed tablets Mobicam (Cipla, Pvt. Ltd). The percentage drug release was shown in Figure 7. Tablet wetting initial Tablet wetting after 28.47 sec Fig. 5. Wetting time of optimized batch F6.

2946 Int J Pharm Sci Nanotech Vol 8; Issue 3 July September 2015 by sublimation technique offers a suitable and practical approach in serving desired objectives of faster disintegration and dissolution characteristics. Accelerated stability study was carried out for optimized formulation F6 which showed no significant difference in the drug content, disintegration time, hardness, friability and in vitro dissolution studies which confirms the stability of the product. Results were statistically analyzed by one-way ANOVA at a p < 0.05. It was found that, the data at any point of time are significant at p < 0.05. Fig. 7. Comparative dissolution profile of F6 with reference. Accelerated stability studies: The tablets were studied for short term stability at 40 C 2 C and 75% 5 % RH conditions for the period of 90 days. Each tablet were individually weighed and wrapped in an aluminium foil and kept at above specified conditioned in stability chamber for 90 days. After 30, 60 and 90 days tablet samples were analyzed. The data obtained from stability studies indicates that batch F6 was stable and optimum formulation. Statistically the data was analyzed by oneway ANOVA at a p < 0.05. It was found that, the data at any point of time are significant at p < 0.05. Conclusions Mouth dissolving tablet of Piroxicam was formulated by using various superdisintegrants such as CrosscarmelloseSodium and Sodium Starch Glycollate in different proportions by sublimating agent like camphor. The solubility of Piroxicam is enhanced by inclusion complexes with β-cd as a drug carrier. Then the prepared inclusion complexes was characterized and evaluated by DSC and FT-IR. The disintegration time of formulation F6 was found to 34.33 seconds. Wetting time studies showed that wetting time was rapid in formulations containing camphor followed by CCS and SSG. It was found that as the concentration of CCS and SSG was increases, then wetting time was reduces. The wetting time of F6 formulation was found to be 30.66 seconds. In vitro disintegration of batch F6 gives rapid disintegration time and wetting time. Drug content was found to be 99.48%. Results of in vitro dissolution data shows that from formulation F1-F9, F6 gives the drug release up to 99.57% within 10 min. So F6 was considered as a best formulation. Batch F6 compared with reference standard Mobicam 20mg marketed tablet which show better release than reference tablet which is an ideal requirement of mouth dissolving formulation. As a result of this study, it may be concluded that the inclusion complexation technique may be useful to enhance solubility, dissolution rate and subsequently bioavailability of poorly soluble drug. The concept of formulating high porous orally disintegrating tablets of Piroxicam inclusion complexes using superdisintegrants Acknowledgements I express my most cordial and humble thanks to management of Hon. Shri. Babanrao Pachpute Vichardhara Trust Group of Institutions, College of Pharmacy, Kashti. Tal-Srigonda, Dist-Ahmednagar, for his necessary help and for his efforts to facilitate the use of the necessary instruments and materials required during the entire course of this research work. I am also grateful to Matrix Pharma Pvt. Ltd, Aurangabad. And Signet Chemical Co Ltd, Bandra Kurla Complex, Mumbai for providing me gift samples of Drug and Polymers. References Ashish P, Harsoliya MS, Pathan JK and Shruti S (2011). A Review Formulation of Mouth Dissolving tablet. Int J Pharm Clinic Sci, 1(1): 1-8. Bhowmik D, Chiranjib B, Krishnakanth, Pankaj, Chandira R M (2009). Fast Dissolving Tablet: An overview. J Chem and Pharm Res, 1(1): 163-177. Jens TC and Rhodes C T (2009). Drug Stability Principle and Practice. Third edition, Volume 107 Marcel Deccker Series, pp-104-11. LachmanL and Liberman HA (2009). The Theory and Practice of Industrial Pharmacy. 3 rd edition. pp-183-193. Patrick M and Sinko J (2009). Physical Pharmacy and Pharmaceutical science. B.I. Publication Pvt. Ltd, 5th edition, pp-232. Prajapati BG and Ratnakar N (2009). A Review on recent Patents on Fast Dissolving Drug Delivery System. Int J Pharm Tech Res, 1(3): 790-798. Radha M, Kanaka DD and Prameela R (2010). Preparation and Characterization of Zafirlukast -Cyclodextrin Complexes using Solid Dispersion Techniques.Int J Pharm Sci Res, 4(1): 88-93. Singh SK, Borkhataria CH, Seth NR, Patel RP, Singh S, and Parmar G (2009). Formulation and in vitro Evaluation of Lansoprazole Micro pellets. Int J Pharm Tech Res, 1(4): 1530-1540. Subrahmanyam CVS (2000). Text Book of Physical Pharmaceutics, 2 nd edition. pp- 51-84. Widjaja B and Setyawan D (2013). Development of Piroxicam Orally Disintegrating Tablets by Freeze Drying Method. Int J Pharm Pharm Sci, 5: 795-798. Address correspondence to: Dr. Sudarshan Singh, Assistant Professor, Dept. of Pharmaceutics, H.S.B.P.V.T, Group of Institutions, College of Pharmacy, Kashti, Ahmednagar 414701, Maharashtra, India. Ph: +91-9765593639; E-mail: sudarshansinghi10@gmail.com