title: Enhancement of oral bioavailability of insulin in humans.
abstract: OBJECTIVE
  The purpose of this study is to investigate oral absorption of 1, 2 and 3 U/kg oral insulin five test products with different particle sizes in comparison with 0.1 U/kg subcutaneous reference formulation.
  
  
  METHODS
  Twenty five healthy volunteers participated in five studies using a two-phase, two-sequence crossover design with washout period of one day. Mean disposition kinetics was determined by non-compartmental analysis using Kinetica program. Absorption kinetics of insulin products were then determined using SIMCYP simulator utilizing ADAM model.
  
  
  CONCLUSIONS
  Dimensional analysis results showed the superiority of formula 4:2 U/kg oral dose with 57 nm particle size over other oral formulations when compared with subcutaneous route. Optimized intestinal permeability coefficients (x10(-4)) of insulin best test and reference formulations were 0.084 and 0.179 cm/sec respectively. Total fraction of insulin dose absorbed (Fa) for the test and reference products were 3.0% and 19% respectively. Subcutaneous product exhibited higher absorption rate and extent than oral insulin. Yet that was compensated by the increase in other factors such as Fa*, Peff* and oral dose, leading to similar insulin plasma levels and similar effect on glucose infusion rates. Oral insulin bioavailability was shown promising for the development of oral insulin product.
authors.affiliation: Jordan Pharmaceutical Manufacturing Co., PO Box 94, Naor, Jordan.
authors.forename: Adnan
authors.initials: A
authors.lastname: Badwan
authors.forename: Mayas
authors.initials: M
authors.lastname: Remawi
authors.forename: Nidal
authors.initials: N
authors.lastname: Qinna
authors.forename: Amani
authors.initials: A
authors.lastname: Elsayed
authors.forename: Tawfiq
authors.initials: T
authors.lastname: Arafat
authors.forename: Munther
authors.initials: M
authors.lastname: Melhim
authors.forename: Omar Abu
authors.initials: OA
authors.lastname: Hijleh
authors.forename: Nasir M
authors.initials: NM
authors.lastname: Idkaidek
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002138:Calibration; D002626:Chemistry, Pharmaceutical / Q000592:standards; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage; D012015:Reference Standards; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin