Development and in vitro evaluation of polar lipid based lipospheres for oral delivery of peptide drugs

Abstract

A 32 factorial design was employed to produce oral sustained release lipospheres prepared by modified double emulsion solvent evaporation technique for Serratiopeptidase (acid-labile enzyme) using wax and polar lipid combination as retardants. The effects of formulation variables selected through preliminary trials namely peptide and stabilizer (Tween® 80) concentration was evaluated by F-test on the drug content and size of lipospheres. The results of analysis of variance tests for both effects indicated that the test is significant (p < 0.05). The effect of Tween® 80 concentration (SSY1- 41.66; SSY2 – 25.30) was found to be higher than peptide amount (SSY1- 3.94; SSY2 – 4.03) on the size and drug content of lipospheres. Characterization was carried out through photomicroscopy, scanning electron microscopy, particle size analysis and in vitro drug release study. The effect of formulation variables on the integrity of enzyme was confirmed by in vitro proteolytic activity. The drug release from lipospheres followed first-order kinetics and was characterized by the Higuchi diffusion and Ritger-Peppas model. Lipospheres having maximum drug content (11.93±0.89) released 3-4% enzyme at pH 1.2 in 4 h. In phosphate buffer, lipospheres showed an initial burst release of 20.89±1.87% to 27.89±2.03% in one hour with additional 73.22±2.36% to 94.75±2.78% in next 12 hours. Thus, peptide loaded lipospheres with desirable characters in terms of maximum peptide content and diffusion release pattern were successfully prepared with formulation optimization approach. Keywords: Cetyl alcohol, Enzyme, factorial design, Lipospheres; Peptide, Serratiopeptidase