Eudragit S100 Entrapped Insulin Microspheres for Oral D...

Eudragit S100 Entrapped Insulin Microspheres for Oral Delivery

Eudragit S100 Entrapped Insulin Microspheres for Oral Delivery
January 21, 2005
Deepti Jain1, A.K.Panda2 and D.K. Majumdar1
1Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences & Research (formerly College of Pharmacy) University of Delhi, Pushp Vihar, Sector-III, New Delhi-110017, India.
2 National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
? AAPS PharmSciTech.
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ABSTRACT
The purpose of this research was to investigate whether Eudragit S100 microspheres have the potential to serve as an oral carrier for peptide drugs like insulin. Microspheres were prepared using water-in oil-in water (w/o/w) emulsion - solvent evaporation technique with polysorbate 20 as dispersing agent in the internal aqueous phase and PVA/PVP as stabilizer in the external aqueous phase. Employment of smaller internal aqueous phase volume (50 ?l) and external aqueous phase volume (25 ml) containing PVA, in the manufacturing process resulted in maximum encapsulation efficiency (81.8?0.9%). PVA-stabilized microspheres having maximum drug encapsulation, released 2.5 % insulin at pH 1.0 in 2 hours. In phosphate buffer (pH 7.4) microspheres showed an initial burst release of 22 % in 1 hr with additional 28 % release in the next 5 hrs. The smaller the volumes of internal and external aqueous phase, the lower the initial burst release. The release of drug from microspheres followed Higuchi kinetics. Scanning electron microscopy of PVA stabilized microspheres demonstrated spherical particles with smooth surface and laser diffractometry revealed a mean particle size (Vm) of 32.51?20 microns. Oral administration of PVA stabilized microspheres in normal albino rabbits (equivalent to 6.6 I.U. insulin /kg of animal weight) demonstrated a 24% reduction in blood glucose level, with maximum plasma glucose reduction i.e. Cmax of 76?3.0 % in 2 hrs and effect continuing up to 6 hrs. The AUC was 93.75% red.h. Thus our results indicate that Eudragit S100 microspheres on oral administration can protect insulin from proteolytic degradation in the GI tract and produce hypoglycaemic effect.
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