Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 495

10.6.3 Vehicles to Improve Absorption
Transportation of peptides across the membrane is improved by the use of different
solvent compositions. Peptides are given in soluble or in dispersed form, and these
vehicles increase solubility of peptides in the membrane. This effect is due to a change
in concentration gradients and a change in partition of peptide between vehicle and
mucosa. Due to the presence of such solvents, partitioning of peptides in lipoidal
mucosa is increased. Examples of such solvent system include the use of 10% lauric
acid in propylene glycol to improve insulin absorption [150] and ethanol at different
concentrations (5% and 30%) to improve absorption of various peptides [145,151] .
Two or more absorption enhancers can be utilized to get a synergistic effect [152] .
10.6.4 Bioadhesive Formulations
The most successful approach for mucosal delivery of peptides has been a bioadhe-
sive formulation. Bioadhesive systems enhance peptide absorption by increasing con-
tact time with the mucosa. To avoid rapid removal of the drug delivery system from
the GI tract, mucoadhesive delivery systems are gaining much more attention and are
being widely investigated for sustained oral delivery of a variety of molecules [153-
156] . Mucoadhesive systems adhere to the GI tract mucosa and release the drug for
a longer period of time; this will increase the overall time period of drug absorption.
Researchers have also been successful in developing delivery systems where bioad-
hesion occurs at a particular site of the GI tract. Bioadhesion of such delivery system
depends on mucous turnover in the particular region of the GI tract. Low turnover of
mucous in the colon and cecum makes these regions best suited for adhesive systems
[157] . Bioadhesive polymers, such as polycarbophil, have also been shown to stabi-
lize peptides by inhibiting proteolytic activity [158-160] . Carbopol 934P, 971P, and
974P strongly inhibited proteolysis of insulin, calcitonin, and IGF-I [65] .
The properties and characteristics of materials used to develop such bioadhesive
drug delivery systems are depicted in Table 10.5 [160] .
Various bioadhesive polymers have been extensively studied for oral delivery of
a wide variety of peptide drugs. Polycarbophil and chitosan derivatives have been
reported to improve the permeation of the peptide drug 9-desglycinamide, 8-arginine
vasopressin (DGAVP) across the mucosa [161] . Advantageous properties such as
good bioadhesion, permeation enhancement, and protease inhibition is imparted in
commonly used polymers by chemical modifications, for example, ethylene diamine
tetra acetate (EDTA)-conjugated chitosan.
10.6.4.1 Bioadhesive Tablets
To avoid the disadvantages associated with conventional tablets, adhesive tablets
have been developed that allow drinking and speaking without major discomfort.
Two techniques are utilized to develop bioadhesive tablets: monolithic and multilay-
ered formulation [162] .
In monolithic tablets, the core is either prepared by direct compression or by wet
granulation followed by coating the core with water impermeable materials on all the