Influences of Sodium Carbonate on Physicochemical Properties of Lansoprazole in Designed Multiple Coating Pellets

Abstract

Lansoprazole (LSP), a proton-pump inhibitor, belongs to class II drug. It is especially instable to heat, light, and acidic media, indicating that fabrication of a formulation stabilizing the drug is difficult. The addition of alkaline stabilizer is the most powerful method to protect the drug in solid formulations under detrimental environment. The purpose of the study was to characterize the designed multiple coating pellets of LSP containing an alkaline stabilizer (sodium carbonate) and assess the effect of the stabilizer on the physicochemical properties of the drug. The coated pellets were prepared by layer-layer film coating with a fluid-bed coater. In vitro release and acid-resistance studies were carried out in simulated gastric fluid and simulated intestinal fluid, respectively. Furthermore, the moisture-uptake test was performed to evaluate the influence of sodium carbonate on the drug stability. The results indicate that the drug exists in the amorphous state or small (nanometer size) particles without crystallization even after storage at 40°C/75% for 5 months. The addition of sodium carbonate to the pellet protects the drug from degradation in simulated gastric fluid in a dose-dependent manner. The moisture absorbed into the pellets has a detrimental effect on the drug stability. The extent of drug degradation is directly correlated with the content of moisture absorption. In conclusion, these results suggest that the presence of sodium carbonate influence the physicochemical properties of LSP, and the designed multiple coating pellets enhance the drug stability.

Eudragit L/HPMCAS Blend Enteric-Coated Lansoprazole Pellets: Enhanced Drug Stability and Oral Bioavailability

“…The drug-layered pellets were prepared by layering the drug suspensions on nonpareil pellets, achieving 20% drug content (22,23). Before an enteric film coating, a HPMC sub-coating with 40% weight gain was layered onto the pellets.…”

“…The blend-coated pellets, regardless of the blend ratio, significantly improved the drug stability. It was ascribed to the decreased moisture absorption that played a key role in the stability of LSP in formulations (13,23). The enteric polymers, due to presence of an ester structure, were susceptible to hydrolysis in the conditions of humidity, affecting the enteric protection in acid medium.…”

Enhanced Dissolution and Stability of Lansoprazole by Cyclodextrin Inclusion Complexation: Preparation, Characterization, and Molecular Modeling

“…In addition, LSP/CD inclusion complexes still got degraded in stress tests although with significantly enhanced stability. Due to highly sensitive to heat and light, a large quantity of alkaline stabilizers, occupying up to 10% (w/w) of LSP, is usually added to the LSP formulations to keep the stability, which, however, can affect the physicochemical properties of LSP (34). Incorporating of additional alkaline agents in the drug layer of the inclusion complex pellets will further increase the stability of the preparation, while the needed amount will be cut down due to the synergistic protective effects of CDs.…”

Preparation and evaluation of enteric coated tablets of hot-melt extruded lansoprazole

“…Also, the presence of the alkalizer in the formulation reduces moisture absorption which further affects its stability. 1 All further studies were performed based on the drug content of each formulation.…”

“…1–3 It is crystalline in nature 4 and sensitive to acid, heat, and light. 5, 6 Solid dispersion is an approach to enhance the solubility of poorly soluble molecules, which involves conversion of the drug from the crystalline to the amorphous phase.…”