Influence of magnesium stearate on the physicochemical and pharmacodynamic characteristics of insulin-loaded Eudragit entrapped mucoadhesive microspheres

Abstract

Effective oral insulin delivery has remained a challenge to the pharmaceutical industry. This study was designed to evaluate the effect of magnesium stearate on the properties of insulin-loaded Eudragit Õ RL 100 entrapped mucoadhesive microspheres. Microspheres containing Eudragit Õ RL 100, insulin, and varying concentrations of magnesium stearate (agglomeration-preventing agent) were prepared by emulsification-coacervation method and characterized with respect to differential scanning calorimetry (DSC), morphology, particle size, loading efficiency, mucoadhesive and micromeritics properties. The in vitro release of insulin from the microspheres was performed in simulated intestinal fluid (SIF, pH 7.2) while the in vivo hypoglycemic effect was investigated by monitoring the plasma glucose level of the alloxaninduced diabetic rats after oral administration. Stable, spherical, brownish, mucoadhesive, discrete and free flowing insulin-loaded microspheres were formed. While the average particle size and mucoadhesiveness of the microspheres increased with an increase in the proportion of magnesium stearate, loading efficiency generally decreased. After 12 h, microspheres prepared with Eudragit Õ RL 100: magnesium stearate ratios of 15:1, 15:2, 15:3 and 15:4 released 68.20 ± 1.57, 79.40 ± 1.52, 76.60 ± 1.93 and 70.00 ± 1.00 (%) of insulin, respectively. Reduction in the blood glucose level for the subcutaneously (sc) administered insulin was significantly (p 0.05) higher than for most of the formulations. However, the blood glucose reduction effect produced by the orally administered insulin-loaded microspheres prepared with four parts of magnesium stearate and fifteen parts of Eudragit Õ RL 100 after 12 h was equal to that produced by subcutaneously administered insulin solution. The results of this study can suggest that this carrier system could be an alternative for the delivery of insulin.

Insulin-loaded mucoadhesive nanoparticles based on mucin-chitosan complexes for oral delivery and diabetes treatment

“…Importantly, the release profiles of the two batches (A1 and A2) were identical and there was no significant difference in the amount of drug released from the two batches of the formulation. The initial fast release could be due to the unencapsulated drug, which adhered to or near the NP surface that quickly detached or succumbed to pressure from the medium (Momoh et al, 2015;Sharma et al, 2016). Clinically, the initial release could be of immense medical advantage in treatment or management of disease, as it constitutes the loading dose of the drug and the subsequent release could serve as the maintenance dose.…”

Progress in spray-drying of protein pharmaceuticals: Literature analysis of trends in formulation and process attributes

“…[85] Finally, magnesium stearate has been applied to the production of microspheres of an oral vaccine of Actinobacillus pleuropneumoniae, [124] probably as agglomeration preventing agent. [167]…”

Novel Capra hircus-Based Miconazole Nitrate-Loaded Mucoadhesive Nanogels for Enhanced Treatment of Oral Candidiasis

“…The active ingredient (drug, MN), lipid matrix, Polysorbate 80 (Tween ® 80) (mobile surfactant), sorbitol (cryoprotectant) and distilled water (vehicle) were used to prepare the MN-loaded nanoparticulate lipospheres by the high-shear melt homogenization method. 13,14 Determination of polydispersity indices and particle size The particle size mean diameter (Z. Ave (nm) and polydispersity indices of nanoparticulate lipospheres formulations (PDI) were determined with a Zetasizer nano-ZS (Malvern Instrument, Worceshtire, UK) fortified with a 10mw He-NE laser using wavelength of 633 nm and a backscattering angle of 173 0 at 25 o C. Before photon correlation spectroscopic (PCS) analysis, deionized water was used to dilute all samples to get a suitable scattering intensity. 15…”