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Phani Ratna Prasanth.G, et al. / International Journal of Advances in Pharmaceutical Research dosing is thus necessary to maintain stable plasma concentration. MATERIALS AND METHODS Materials Dexlansoprazole, a gift sample from labs of Alkem, sugar spheres, PVP K 30, HPMC E5, dibasic sodium phosphate, Light magnesium carbonate, sodium lauryl sulphate, Mannitol, Eudragit L 100 55, HPMC P 55 PEG 4000, Triethyl citrate, diethyl phthalate, cetyl alcohol, talc, titanium dioxide, iso propyl alcohol were obtained as a gift sample from Alkem research center. Methods Preparation of Dexlansoprazole 30 mg Delayed release Pellets 6, 7, 8, 9 Drug loading Weigh all the ingredients as per the given formula in table 1 and prepare the drug solution. Take 500 ml of purified water in beaker and kept for stirring under mechanical stirrer. Specified quantities of PVP K30, HPMC E5, dibasic sodium phosphate, Magnesium carbonate and SLS were added slowly and stir it for a uniform suspension. Then drug was added in the above solution and stirring was continued for 30 mins to form a vortex of the solution. Now pass the dispersion using Nylon cloth of mesh no 200. The solution is now ready for drug loading. Finally the drug is loaded using the dispersion over sugar spheres in the chamber of FBP. Barrier coating: (Sub coating) 5 Sub coating was done to protect and also for increasing the stability of a drug. Mechanical strength of pellets is also increased. In order to prevent interaction with functional groups contained in the enteric film coat, it is one of the advantages to combine enteric coatings with sealing coats made up of cellulose derivatives. 500gm water is taken in a beaker and kept it for stirring, specified quantities of PVP K30, HPMC E5, dibasic sodium phosphate, magnesium carbonate and mixed well for 30 min. Add slowly mannitol to the coating solution under stirring for 15 min. After formation of a suspension the solution is ready for sub coating and the drug loaded pellets were coated by using Fluidized bed coater. Enteric Coating 10 Step I: 300ml of IPA and 900 ml of acetone were taken in a beaker and kept for stirring under a mechanical stirrer. Step II: All the ingredients should be weighed accurately and should be passed through 200# for proper formation of dispersion. Step III: In another portion of solution add talc and titanium dioxide and stir it. Step IV: Now step II form was added slowly to step I and stirring was done for 20 min until it forms a uniform mixture. Add plasticizer to the above dispersion. Step V: Add dispersion step IV to step III under continuous stirring to form a homogenized mixture. Now filter through a nylon cloth. Now the filtered solution is ready for enteric coating and check the pH of the solution. Step VI: enteric coating using the dispersion of step V over the barrier coated pellets with the help of fluidized bed coater. Wurster insert and a bottom spray gun. Spread of the solution was carried out at at atomization pressure of 2 kg/cm 2 , an inlet temperature of 35 o C, spray rate of 6 ml/min and a fan speed of 7 to 9. Up on completion of spraying, the various loading on sugar spheres were further dried at 60 o C inlet temperature for 5 min and the in process parameters were given in table 1. The final end product was then sieved on top of a 20-mesh screen to eliminate fines. Evaluation of Pellets 1,12 Evaluation of pellets must be done to obtain product performances. Evaluation at different stages during manufacturing process were as follows Acid resistance: amount of drug resisted after 2 hr in acid was 99.75%. Pellets size analysis: Formulated Dexlansoprazole delayed release pellets size change during different stages such as drug loading, Barrier coating and enteric coating of pellets were shown in table no 3 Particle size distribution: This was done for proper coating. Particle size was determined by using SEM. Samples of F9 formulation were mounted on metal tubes and SEM photograph was taken as shown in figure 5. Determination of drug contents: Enteric coated pellets of Dexlansoprazole 30 mg were transferred to 100 ml vol. flask, added 70 ml of methanol and sonicate for 15 min with intermittent shaking and dilute to volume with methanol. Filter through 0.45µ filter and further dilute 5 ml of this solution to 100 ml with mobile phase. Results were tabulated in table 4. Invitro dissolution studies: An invitro dissolution study for the finished product formulation was carried out using dissolution USP method I (basket) for Dexlansoprazole delayed release pellets. The dissolution medium consisted of 900 ml of pH 1.2 buffer maintained at a temp of 37+0.5 o C and was run for 2 hr initially and release should not be more than 10%. Transfer the weighed pellets equivalent to 30 mg of Dexlansoprazole in to each of six jars. After 2 hrs the previous acid medium was replaced with 900 ml of pH 6.8 buffer and release study was done. IJAPR / May. 2012/ Vol. 3 / Issue. 5 / 907 - 913 908
Phani Ratna Prasanth.G, et al. / International Journal of Advances in Pharmaceutical Research Calculations: % of Dexlansoprazole A T W Std 5 900 P Dissolved = -----×-------×------×------×------×100 A s 100 50 LC 100 Where, A T : average of the area counts of the Dexlansoprazole peak obtained from the chromatograms of Test preparation A s: average of the area counts of the Dexlansoprazole peak obtained from the chromatograms of the standard preparation W std : Weight of Dexlansoprazole working standard in mg P: potency of Dexlansoprazole working standard (% on as is basis as dexlansoprazole) LC: label claim of Dexlansoprazole mg per capsule. Volume with drawal: 5 ml and replaced at same temp Dilution Factor: 100 Bath volume: 900 ml After specified interval withdraw sample from a zone midway between the surface of the medium and top of the rotating blade and not less than 1 cm from the vessel wall and filter through 0.45 micron membrane filter. Differential Scanning calorimetry studies: 11 DSC scan of about 5 mg using an automatic thermal analyzer system performed accurately weighed of Dexlansoprazol, API and polymers Eudragit and HPMC of 1:1 in ratio respectively. Figure no 2, 3, 4 shows the DSC thermographs of pure drug of Dexlansoprazole and polymers. Thermographs obtained by DSC studies revealed that the melting point of pure drug is 145 O C and that the polymer and pure drug shows sharp endothermic peak at 142.3 O C. Eudragit shows sharp endothermic peak at 138 o C. From this it may be concluded that the drug is in the formulation without interacting with the polymer and excipients. Stability studies: The stability studies of the optimized capsule formulation F9 were carried out according to ICH guide lines at 40+2 o C/75+5 % RH for two months by storing the sample in stability chamber (thermo lab). Samples were collected at 15 days interval. RESULTS & DISCUSSION In the present study delayed drug delivery of Dexlansoprazole were successfully developed by enteric polymers which offer a suitable and practical approach in serving desired dissolution characteristics with increased bioavailability. The enteric coated pellets size was found to be increased during drug loading, barrier coating and enteric coating of pellets as shown in table 3. Among all the formulations F9 shows invitro dissolution profile within acceptable official limit. Particle size distribution was also determined for proper coating and the micrograph of formulation F9 was shown in figure 5. DSC studies with other excipients revealed that there was no interaction and also selected formulation was stable after stability studies. DISCUSSION In coating process the enteric coating was done with the percentage build up of 25-28% with 8% sub coating. Acid resistance test failed up to 26% but at 28% build up acid resistance test passed. But for safer side we coated up to 30% with 8% sub coating. Based on the results Formulation F9 was found to be satisfactory as it has excellent release properties where it has shown an excellent stability. There was no significant change in invitro release profile. It shows that the formulation F9 was stable. Also from the stability studies it was confirmed that it was stable under the desired conditions which was shown in fig 6 CONCLUSION The aim of the present study was to formulate and evaluate delayed release pellets of Dexlansoprazole by enteric coating. It is an acid liable drug so it is degraded at acidic pH of stomach. So an attempt was made to stabilize the drug and by using alkaline agent magnesium carbonate. Finally enteric coating was given to bypass the stomach. The enteric coating was carried out by using enteric polymer HPMC P 55 S. the core pellets were prepared using suspension layering technique in fluid bed process. Sub coating was given to core pellets to avoid direct contact of drug with enteric coating materials. An average weight build up of 8% w/w was given to core pellets. Enteric coating was given to sub coated pellets at an average weight build up of 30% w/w of sub coated pellets and the acid resistance profile is seen. Stability studies were also conducted for 2 months and it was concluded that the drug release from F9 formulation was best suitable formulation. ACKNOWLEDGEMENTS The authors wish to thanks the principal Dr. Y.Haribabu; I place on record my gratitude to Dr.K.Santhi, Dr. C.I.Sajeeth and management of Gracecollege of pharmacy, Kerala for continuous support, encouragement and excellent facilities. Very special thanks to management of Alkem Research centre group for gift samples of drug and providing excellent research facilities. IJAPR / May. 2012/ Vol. 3 / Issue. 5 / 907 - 913 909
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