title: 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® RL 100 entrapped mucoadhesive microspheres. Microspheres containing Eudragit® 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 alloxan-induced 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® 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® 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.
authors.affiliation: a Drug Delivery Research Unit, Department of Pharmaceutics , University of Nigeria , Nsukka , Enugu State , Nigeria.
authors.forename: Mumuni A
authors.initials: MA
authors.lastname: Momoh
authors.affiliation: a Drug Delivery Research Unit, Department of Pharmaceutics , University of Nigeria , Nsukka , Enugu State , Nigeria.
authors.forename: Franklin C
authors.initials: FC
authors.lastname: Kenechukwu
authors.affiliation: a Drug Delivery Research Unit, Department of Pharmaceutics , University of Nigeria , Nsukka , Enugu State , Nigeria.
authors.forename: Petra O
authors.initials: PO
authors.lastname: Nnamani
authors.affiliation: a Drug Delivery Research Unit, Department of Pharmaceutics , University of Nigeria , Nsukka , Enugu State , Nigeria.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Umetiti
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D005260:Female; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D054327:Lubricants / Q000737:chemistry*; D008297:Male; D008863:Microspheres; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013229:Stearic Acids / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D054327:Lubricants; D011109:Polymethacrylic Acids; D013229:Stearic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C031183:stearic acid; D048271:Chitosan
keywords: Blood glucose reduction; Eudragit RL 100; insulin; magnesium stearate; microspheres; oral administration