Biomedical Engineering Reference
In-Depth Information
Table 12.2 Absorption-Enhancing Systems Used in Rectal Drug Administration of
Proteins and Peptides
Enhancer
Protein or Peptide
Bile acids
Heparin [175,180] , insulin [178]
Ethylenediamine tetra-acetic acid
Des-enkephalin--endorphin [179]
Enamine derivatives
Lysozyme [180] , insulin [181-184]
Nonionic surfactants
Calcitonin [163]
Nitric oxide donor
Insulin [167]
Nonsteroidal antiinflammatory drugs
Insulin [188,189]
Salicylate, 5-methoxysalicylate
Erythropoietin [190] , heparin [191] , dextran
[192] , insulin [193,194]
vehicles. Hydrophilic cyclodextrins increase the bioavailability of drugs in different
administration routes by increasing the solubility, dissolution rate, and wettability of
poorly water-soluble drugs and by preventing the degradation or disposition of chem-
ically unstable drugs in GI tracts, as well as during storage. It perturbs the membrane
fluidity to lower the barrier function, which consequently enhances the absorption of
drugs, including peptide and protein drugs, through the rectal mucosa. It also releases
the included drug by competitive inclusion complex formation with third components
(bile acid, cholesterol, lipids, etc.) and inhibits P-glycoprotein-mediated efflux of the
drug from intestinal epithelial cells.
Cyclodextrins were found to enhance the permeability of proteins such as insu-
lin, recombinant human granulocyte colony-stimulating factor (rhG-CSF) [195] ,
and human chorionic gonadotropin (hCG) [170] through the rectal epithelium cells.
With respect to insulin suppository, the absorption of insulin from the rectum of
rabbits after the administration of hollow-type suppositories containing insulin and
cyclodextrins significantly increased, with a marked decrease in the glucose levels
observed. To expand the practical use of other enhancers, vital issues such as their
safety and local irritation as well as variability of the efficacy should be tackled.
Surfactants Surfactants are capable of improving various pharmaceutical proper-
ties, such as wettability, solubility, dissolution rate, and miscibility, and are useful
for improving the rectal bioavailability of impermeable drugs across biomembranes,
including p -aminobenzoic acid (PABA), sulfaguanidine, and proteins [196,197] . The
enhancing effects of surfactants on rectal absorption of proteins such as insulin and
calcitonin [163] in various formulations have been reported: BL-9 enhanced the rec-
tal insulin absorption in suppository (witepsol W35) and solution [185] . Recently,
the use of Tween 60 as an absorption enhancer for insulin suppository in rabbits
was demonstrated [198] . The mechanisms through which surfactants enhance rec-
tal absorption of poorly membrane permeable drugs are likely to be solubilization
of membrane lipids, sequestration of Ca 2 , and protein release from rectal mucosa.
Solvent drag effect in drug intestinal absorption was studied on drug and D 2 O
absorption clearances [199] .
Search WWH ::




Custom Search