Formulation Development, Process Optimization, and In Vitro Characterization of Spray-Dried Lansoprazole Enteric Microparticles.

Chintan Vora

doi:10.3797/scipharm.1501-08

Abstract

This research focuses on the development of enteric microparticles of lansoprazole in a single step by employing the spray drying technique and studies the effects of variegated formulation/process variables on entrapment efficiency and in vitro gastric resistance. Preliminary trials were undertaken to optimize the type of Eudragit and its various levels. Further trials included the incorporation of plasticizer triethyl citrate and combinations of other polymers with Eudragit S 100. Finally, various process parameters were varied to investigate their effects on microparticle properties. The results revealed Eudragit S 100 as the paramount polymer giving the highest gastric resistance in comparison to Eudragit L 100-55 and L 100 due to its higher pH threshold and its polymeric backbone. Incorporation of plasticizer not only influenced entrapment efficiency, but diminished gastric resistance severely. On the contrary, polymeric combinations reduced entrapment efficiency for both sodium alginate and glyceryl behenate, but significantly influenced gastric resistance for only sodium alginate and not for glyceryl behenate. The optimized process parameters were comprised of an inlet temperature of 150°C, atomizing air pressure of 2 kg/cm2, feed solution concentration of 6% w/w, feed solution spray rate of 3 ml/min, and aspirator volume of 90%. The SEM analysis revealed smooth and spherical shape morphologies. The DSC and PXRD study divulged the amorphous nature of the drug. Regarding stability, the product was found to be stable under 3 months of accelerated and long-term stability conditions as per ICH Q1A(R2) guidelines. Thus, the technique offers a simple means to generate polymeric enteric microparticles that are ready to formulate and can be directly filled into hard gelatin capsules.

Highlights

Lansoprazole (LSP), a BCS Class II compound, belongs to the category of compounds called proton pump inhibitors (PPIs)
We have employed neutralized by the addition of sodium hydroxide (NaOH) to solubilize the enteric polymer for the preparation of microparticles [13]
With mounting awareness of spray drying techniques for the preparation of drug microparticles commercially, the usefulness of it has prudently entered into the realms of research and industry for understanding the process or formulation variable rationally

Summary

Introduction

Lansoprazole (LSP), a BCS Class II compound, belongs to the category of compounds called proton pump inhibitors (PPIs). LSP has an inhibitory effect against Helicobacter pylori which contributes in augmenting the effect of antibiotics in the treatment of infection [4, 5] Regarding their mechanism, PPIs get converted into the active sulfenamide metabolite by the acidic environment of parietal cells which further reacts with cysteins of the enzyme H+/K+ ATPase. PPIs get converted into the active sulfenamide metabolite by the acidic environment of parietal cells which further reacts with cysteins of the enzyme H+/K+ ATPase This causes inactivation of the sulphydryl group of the proton pump, thereby reducing the hydrogen ion concentration. This conversion of LSP into the active form should occur inside the gastric cells, it should be absorbed in an intact form from the intestinal tract [1, 3, 6]

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Conclusion