Preparations And Studies Of Orally Disintegrating Tablet Of Lansoprazole

Objectives:Lansoprazole,a proton pump inhibitor used for the treatment of ulcer,is one of the effective drugs in the clinical treatment of digestive disease.It has a poor water solubility and is sensitive to humidity and thermal,unstable in the acid.So Lansoprazole often comes as an enteric-coated capsules and lyophilized preparation.Orally disintegrating tablet is a novel immediate-release solid dosage form.It could disintegrate into small particles in the oral cavity rapidly,which enter the body by swallowing.This study would like to make Lansoprazole orally disintegrating tablets,which would improve the compliance to those patients who have difficulty in swallowing with peptic ulcer.Methods:1 In this prescription,pellet cores were prepared by the method of extrusion-spheronization,using microcrystalline cellulose as diluents,sodium carboxymethyl starch as disintegrants,aqueous solution of povidone with tween-80 was used as adhensives.Then investigated the pellet in accordance with the standards of immediate-release granules and took the cumulate release rate within 45 minute in PBS as an index.At last selected the best prescription of pellet through L9（33）orthogonal experiment design.And Lansoprazole enteric-coated particles were prepared by spraying the coating at the bottom fluidized bed,using 3% HPMC aqueous ethanol solution（80%）as barrier coating material,L30D-55 aqueous dispersion as enteric-coated material,which contains X as plasticizer.In order to determine the coating process optimization,investigated the fluidized bed coating process from the single factor,such as the temperature of inleting air,the pressure of spraying and the speed of spray;Investigate the weight gain of the isolation layer and enteric layer with the indicators contained cumulative release in buffer solution and acid resistance.2 Mix the enteric-coated granules with appropriate excipients,and tablet directly with microcrystalline cellulose as diluents,PVPP as the disintegrant,magnesium stearate as the lubricant,and aspartame as the flavoring agent.Selected the best prescription of pellet through single-factor affecting the disintegration time analysis and L9（33）orthogonal experiment design.In the meanwhile established suitable method of determinating vitro disintegration time for Lansoprazole orally disintegrating tablets.3 The quality control study of Lansoprazole orally disintegrating tablets: establish HPLC methods for the content uniformity,determination of content and related substance.Investigated the release of enteric-coated granules and orally disintegrating tablets with the methods about Lansoprazole enteric-coatde capsules in the New Drug Official Standard.In the meantime,carried out the related methodological study,prepare Lansoprazole orally disintegrating tablets in accordance with the best prescription,and then study the stability of preparation by the influencing factor test and accelerate test with the indexes of dissolution,content and the related substance.4 Beagles for test animals,commercial preparations for the reference,a single-dose,two-treatment,two-sequence and randomized crossover study was carried out on four adult beagle dogs.Establish HPLC method to determine Lansoprazole in the plasma of beagle dogs,calculate the pharmacokinetic parameter of Lansoprazole and study the relative bioavaibility and the bioequiavailability.Results:1 The best formula of the pellet cores is selected through the single factor test and orthogonal test design: Lansoprazole 17 mg,microcrystalline cellulose 68 mg,M 6 mg,anhydrous sodium carbonate 4 mg,PVP aqueous solution（15%）containing Tween-80（1%）;Isolation layer coating liquid is identified as HPMC（3%）ethanol water solution（80%）,coating technology;Temperature of in air 40℃,pressure of spray 0.03 MPa,spray speed 0.7 mL·min-1;Enteric layer coating liquid composition is as follow: Eudragit L30D-55,X,talcum powder,coating technology: temperature of in air 35℃,pressure of spray 0.03 MPa,spray speed 1 mL·min-12 Through the single factor study and orthogonal experiment with the indexes of disintegration time and friability,the optimal prescription of orally disintegrating tablet of Lansoprazole was determined as follows: Lansoprazole enteric-coated granules 50%,MCC30%,PVPP15%,aspartame1%,mannitol 3.7%,magnesium stearate 0.3%.First mixed the excipients mentioned above,then mixed with the enteric-coated granules,and tabletted the powder directly to prepare the Lansoprazole oral disintegrating tablet.The hardness of the tablets was 3-3.5kg.3 Established the methond of determinating release of pellet cores,enteric-coated granules and Lansoprazole oral disintegrating tablet with UV.And the wavelength was 284 nm where without any interference from excipients and solvents.This methond was verified to determinat the dissolution of Lansoprazole orally disintegrating tablets by methondology.4 Established the methond of determinating content,uniformity of content and related substances of Lansoprazole,wavelengths were 284 nm.This methond was verified as simple,accurate and sensitive,and suitable for the quality control of Lansoprazole,without interference from excipients and solvents.The specificity test was also carried out for the determination of the related substances.The impurities produced by the damages of acid,alkali,light,high temperature and oxidation didn’t interfere the determination of main drug.5 In the influence factor test,the samples were absorbent seriously and the release slowed down after placed for ten days in the relative humidity of 92.5% and 75.0%.The granules in the tablet grew dark,the impurities increased obviously,the content reduced significantly with the irradiating glare as 4500 Lx,the relative humidity as 92.5% and the temperature as 60℃.The content and related substances didn’t change obviously in the temperature of 40℃ for ten days.The stability tests showed this preparation was unstable to moist,heat and light,therefore the tablets should be stored in low temperature and avoidance of light and moist.6 Established an HPLC method for the determination of Lansoprazole blood drug concentration,wavelength was 284 nm.Blank plasma was no interference on determination of main drug.Compared with reference formulation,AUC_0→∞ of self-made tablets was increased,the relative bioavailability of tested formulation was 116.30%.Conclusion: The prescription of Lansoprazole orally disintegrating tablets and preparation process is simple,feasible,good reproducibility,rapid disintegration in the oral cavity and possible to improve patient compliance.The determination methonds built for disintegration time,dissolution,content and related substances provide safeguard for the quality of the preparation.