Preparation and evaluation of oral multiparticulate formulations of acid-labile drugs

Acid-labile drugs are easily degraded in acidic medium, which have been mainly formulated as enteric-coated dosage forms for oral administration. The objective of this study was to prepare oral multiparticulate formulations of acid-labile drugs, using ilaprazole, lansoprazole and rabeprazole sodium as model drugs. The influence of drug solubility and core type on drug layering, swelling, acid resistance, and drug release of the delayed-release pellets and pellet-tablets was investigated using lansoprazole and rabeprazole sodium as drug pair. The influence of subcoat on water vapor sorption, acidic medium seeping, acid resistance of the delayed-release pellets and pellet-tablets, as well as the influence of top-coat on pellet compression were investigated using ilaprazole as the model drug. 

Three commercially-available cores (CP-102, Nonpareil-105, and PF 053) and one laboratory made cores were used in the study with MCC% w/w in the cores in descending order of CP-102 (100% MCC) > laboratory made cores (45% MCC) > Nonpareil-105 (30% MCC) > PF 053 (0% MCC). Rabeprazole sodium was more influenced by a decreasing pH of the medium than lansoprazole. Rabeprazole sodium was dissolved in the binder solution with higher dissolved content (15.67%) and viscosity (92.05 mPa.s), compared with lansoprazole, which was insoluble in the drug suspension with 4.86% of dissolved content and viscosity of 80.24 mPa.s. The coating levels of rabeprazole sodium drug pellets with 45% MCC cores and 0% MCC cores were lower than those of lansoprazole drug pellets made in the same cores, and much lower than those of both drug pellets from 100% MCC cores and 30% MCC cores, which implied that the 45% MCC cores had the least mechanical strength, and that 0% MCC cores were strong enough for layering of lansoprazole, but not strong enough for layering rabeprazole sodium. When the core loss dominated, the coating level by weight decreased while the actual coating level increased. When drug loss dominated, the coating level by weight decreased and actual coating level also decreased. The decrease in coating level / actual coating level reflected an increase in core loss. The visible dents, broken parts, and cracks on the surface of rabeprazole sodium drug pellets layered from 0% MCC cores and 45% MCC cores provided sufficient evidence for core crumbling or breakage. 

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Preparation and evaluation of oral multiparticulate formulations of acid-labile drugs
Thesis FANG HUANG 2017
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