Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 503

faces except the face which is in contact with the mucosa. Water-impermeable materials
include Teflon, ethyl cellulose, cellophane, hydrogenated castor oil, and so on. Such a
system begins unidirectional drug flow toward the mucosa and avoids drug loss [163] .
Multilayered tablets are prepared by compressing the tablet layer by layer. They
are generally composed of an adhesive layer that faces the mucosa, a rate-controlling
layer, and a drug layer, with the drug layer sandwiched between the adhesive layer
and rate-controlling layer. The drug is also incorporated into the adhesive layer to
give drug release direct to the mucosa. This approach is useful to deliver drugs either
systemically or locally [164] .
10.6.4.2 Bioadhesive Patches
Mucoadhesive intestinal patches have also been investigated for oral delivery of
conventional drug molecules [165] . Similar to methods employed with bioadhesive
tablets, monolithic, and multilayered techniques are utilized to develop bioadhesive
patch formulation. Methods to manufacture such patches include solvent casting and
direct milling, where direct milling may or may not utilize the solvent. The backing
membrane is applied to the monolithic or multilayer sheet to get unidirectional drug
release and to avoid deformation and disintegration after application. In solvent cast-
ing, the bioadhesive solution is casted on the backing membrane, which is mounted
on stainless steel. Here the drug can either be incorporated into the adhesive layer or
sandwiched between the adhesive layer and the backing membrane. Casting is fol-
lowed by drying and cutting the patches. On the other hand, direct milling involves
uniform mixing of the drug and an adhesive polymer, followed by compressing the
mixture to get desired thickness and cut to appropriate size [165-167] .
10.6.4.3 Bioadhesive Gels
Adhesive gels may also be tried to deliver drugs via the mucous membranes of the GI
tract. Adhesive gels prolong the residence time of the delivery system to the site and
thus improve drug absorption. Site-specific gelling polymers are utilized to get the
drug release at the desired location or at the absorption window of the drug [168-170] .
Such a site-specific approach can be utilized to protect the peptide drug from
enzymes and an acidic environment.
10.6.5 Penetration Enhancers
Absorption of proteins and peptides is improved by the use of different penetra-
tion enhancers. Penetration enhancers affect the mechanism by which the drug is
absorbed through the mucosa. Transcellular or paracellular pathways of drug absorp-
tion are significantly affected by the use of penetration enhancers in the formulation.
Penetration enhancers may enhance the absorption of drugs preferentially in some
specific region of the GI tract [171] . By changing the lipid orientation and arrange-
ment within the cell wall, surfactants and fatty acids ease the transport of peptides
and proteins through the membrane. Penetration enhancers may act by increasing
the thermodynamic activity of peptide drugs. This may be affected by the vehicle