Abstract

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Purpose: lansoprazole has been found to form inclusion complexes with Hp-β- cyclodextrin (Hp-β-CD) in solid state. The present study was undertaken to determine a suitable method for scaling up lansoprazole Hp -β-CD inclusion complex formation and to evaluate the effect of some parameters on the efficiency of complexation. Method: The solid inclusion complexes of lansoprazole and Hp-β-cyclodextrin were prepared at a molar ratio of 1:1 and 1:2 by mixing, kneading, on small and large scales. Characterization was performed using infrared spectroscopy, X-ray diffractometry, and dissolution studies. In vitro release studies were carried out in phosphate buffer (pH 6.8). Result: Kneading methods of preparation of complexes were found to be useful in increasing the solubility of lansoprazole except mixing method where the rise in solubility was not significant. Both kneading and co-precipitation methods in 1:2 molar ratios were found to be equally effective in improving the solubility of lansoprazole. The formation of inclusion complexes was evident in these formulations as shown by IR and XRD studies. But when carried out on a large scale. Moreover percent recovery of complexes in the kneading method was found to be 98.76% . Conclusion: Drug content studies, IR spectroscopic studies, X-Ray diffractometry studies and in vitro dissolution study data indicated that inclusion complexes prepared by kneading method in 1:2 molar ratios were suitable for improving the solubility of lansoprazole. The same formulation was prepared at large scale and optimum formulation conditions were established. Keywords: lansoprazole, Inclusion complexes,Hp- β-cyclodextrin, Kneading method.

One of the most important tasks in drug discovery and development is to enhance the oral bioavailability by improving the dissolution of poorly water soluble drugs. The formulation of hydrophobic drugs as solid dispersions is a significant area of research aimed at improving their dissolution and thus enhancing the bioavailability [16].4]. it need to be protected from the destructive effects of gastric acid when administered orally. drug-induced ulcers [7]. LPZ is unstable in the stomach.2.2-trifluoroethoxy)-pyridine. solubilization. Cyclodextrins (CDs) are cyclic oligosaccharides. gastric acid. CDs have been found to be very useful in enhancing the solubility of poorly water-soluble drugs owing to the formation of inclusion complex of the drug in its hydrophobic cavity2-6.2]. the solubility of drug can be improved by changing drug crystallinity to an amorphous state and reducing particle size for better wettability [17].4. but they all delay LPZ absorption [10–12]. Various types of enteric coating have been developed to protect LPZ. symptoms of gastroesophageal reflux disease [5]. This is not only attributed to the genotype of CYP2C19 involved in the metabolism of LPZ in the patients [14. including peptic ulcers (duodenal and gastric) [3. LPZ belongs to class II drugs of the Biopharmaceutical Classification System (BCS) characterized by practically high permeability. is a proton pump inhibitor that acts on the membrane H+/K+-ATPase in gastric parietal cells [1. It has a hydrophobic central cavity and a hydrophilic outer surface1. oral administration of LPZ has been known to show a marked individual variation of absolute bioavailability in human subjects [13]. and solid dispersion formation are the approaches most often used to reach this goal. poor solubility. However. i.INTRODUCTION. In addition. Salt formation. the presence of the carrier might also cause the creation of a microenvironment in which the drug solubility is improved [18. hypersecretory syndromes like Zollinger–Ellison [8] and Helicobacter pylori infection [9]. there is a possibility that it is not well dissolved in the small intestine from which most drugs are absorbed into the systemic circulation [8]. β- .2-pyridinyl] methyl] sulfinylsulphinyl]-1H-benzimidazole).linkages produced by the action of the cyclodextrintrans-glycosidase enzyme on a medium containing starch. particle-size reduction. On the other hand. (2-[[[3-methyl-4-(2.19].e. LPZ can come as a tablet. even if it is protected from the destruction of gastric acid. In fact. but also to the gastric degradation. an oral suspension and a disintegrating capsule [10]. The most common natural CDs are α-cyclodextrin. Therefore. containing a minimum of six D-(+)glycopyranose units attached by α-1. Lansoprazole (LPZ). In the solid dispersion system.15].. the dissolution and limited solubility of LPZ in water [8]. erosive esophagitis [6]. It has been widely used for the treatment of a variety of acid-related disorders.

The resultant dispersion complex was pulverized. Potassium dihydrogen phosphate (35. which was then dried under vacuum at room temperature.10 but cost and toxicity factors poses limitation in their use. and sieved through 0.. Preparation of solid dispersion complex Dispersion complexes of LSP withHP β-CD containing 1:1 ratio was prepared by the kneading method. collected and stored in a closed container away from the light and humidity until use. . EXPERIMENTAL Materials Hydroxy propyl β. Method Preparation of physical mixtures The physical mixtures of lansoprazole withHP β-CD were prepared by mixing appropriate amounts (1:1 ratio) in a mortar using the geometric dilution technique. The resulting mixtures were sieved through 0.Cyclodextrin gifted by glain mark mumbai and Lansoprazole was received from Cipla private Ltd. Amongst the various available CDs. β-cyclodextrins (βCD) are the cheapest and are nontoxic for oral use11.25mm sieve and stored in a closed container away from the light and humidity until use.cyclodextrin and γ-cyclodextrin. and eight glucose units. seven.8 which may produce better solubility when complexed9.084 g) and disodium hydrogen phosphate (28.8. Indore. India. Appropriate amount of β-CD and HPC were added to DMP in a mortar and the powder mixture was wetted with a minimum volume of water and kneaded thoroughly with a pestle to obtain a paste. which are formed by six. respectively. and double distilled water was used.80 g) were dissolved in 1000 ml of water to produce phosphate buffer of pH 6. as gift samples. All the reagents and solvents were analytical grade.25mm sieve. Apart from these naturally occurring CDs. various derivatives are also available7.