Author(s): Rajesh Kumar1, DK.Majumdar1*, AK. Panda2 and DP. Pathak3
Composite polymeric human insulin loaded microparticles were prepared using triple emulsion solvent evaporation technique with 1% PVA as a stabilizer and 0.1% w/v hydrophilic chitosan in the external aqueous phase, PLGA in internal organic phase and 4-6% w/v Eudragit in external organic phase. The mean diameter of the microparticles was in the range of 1-6 μm. Higher amount of Eudragit polymer provided the maximum drug encapsulation. IVR profile showed that Eudragit L 100 particles have more initial burst release (19.75%) in1 hr. in and % cumulative release (85.15%) in PBS pH 6.8 than Eudragit S 100 particles showing initial burst release (10.31%) in1 hr.and % cumulative release (74.56%). Eudragit L 100: Eudragit S 100 (1:1) particles at pH 6.8 throughout 12 hr. showed more initial burst release (18.45%) in1 hr.and % cumulative release (84.14%) than Eudragit L 100 : Eudragit S 100 (1:1) particles at pH 6.8 in first 1 hr. and remaining 11 hr. at pH 7.4. Eudragit L 100 : Eudragit S 100 (1:1) particles at pH 7.4 throughout 12 hr. showed less initial burst release (10.66%) in 1 hr. and % cumulative release (78.94%). IR spectra suggest the entrapment of insulin in composite polymeric microparticles. CD spectra suggesting maintenance of secondary structure of insulin. SDS-PAGE confirmed that the structural integrity of the drug was maintained during encapsulation. Stability studies results showed that insulin loaded particles stored at 4?C were more stable than particles stored at 25 ?C and at -20 ?C. In-vitro caco-2 cell line studies show that % viability was more for particles than pure insulin solution. TEER values of caco-2 cell monolayer was found to be more for particles at pH 6.8 than particles at pH 7.4.