Nasal preparations absorption enhancers

Since the concentrations of insulin to be administered in the sheep model would have been large, the insulin-loaded chitosan nanoparticles were not investigated in that model. However, the pharmacodynamics and pharmacokinetics of various insulin-chitosan preparations were compared with postloaded insulin-chitosan nanoparticles. It was found that chitosan solution and chitosan powder formulations were far better, with the chitosan powder formulation showing a bioavailability of 17% as against 1.3 and 3.6% for the chitosan nanoparticles and chitosan solution [72], The effects of the concentration and osmolarity of chitosan and the presence of absorption enhancers in the chitosan solution on the permeation of insulin across the rabbit nasal mucosa in vitro and in vivo were investigated, and the same... 

Chitosan microspheres were shown to enhance nasal bioavailability of several peptide drugs such as insulin and goserelin. A simple chitosan-insulin powder formulation provided about 20% of absolute insulin bioavailability in sheep [96], Improved bioavailability (of 44%, in rats) was obtained when insulin was loaded into chitosan microspheres prepared with ascorbyl palmitate as cross-linking agent [91]. Chitosan microspheres have also been shown to improve nasal goserelin absorption providing about 40% bioavailability relative to goserelin intravenous application [9],... 

Nasal drug absorption can be accomplished by use of prodrugs, chemical modification of the parent molecule, and use of physical methods of increasing permeability. Special excipient used in the nasal preparations comes into contact with the nasal mucosa and may exert some effect to facihtate the drug transport. The mucosal pores are easier to open than those in the epidermis. The following characteristics should be considered in choosing an absorption enhancer ... 

The combined effect of (3-CyD with absorption enhancers such as sodium glycocholate or Azone on the nasal absorption of human fibroblast interferon- 3 in powder form in rabbits has been described. HP- 3-CyD was useful as a biocompatible solubilizer for lipophilic absorption enhancers involved in the nasal preparations of peptides.When insuUn was admiifistered nasally to rats, simultaneous use of an oily penetration enhancer, HPE-101, (l-[2-(decylthio)-ethyl]azacyclopentane-2-one) or oleic acid solubilized in HP-(3-CyD showed a marked increase in serum immuno-reactive insulin levels and marked hypoglycemic (Figure 40.11). The potentiation of the enhancing effect of HPE-101 by HP-(3-CyD can be explained by the facilitated transfer of HPE-101 into the nasal mucosa. Studies on the release of membrane proteins and scanifing electron microscopic observations of rat nasal mucosa indicated that the local mucosal damage due to the combination with HP- 3-CyD may not be serious obstacles to their safe use. 

Me, T., Abe, K., Adachi, H. et al. Potential use of 2-hydroxypropyl-(3-cyclodextrin in designing nasal preparations of insulin involving lipophilic absorption enhancer HPE-101. Drug Deliver. Syst. 1992, 7, 91-95. 

Section 16.2.6 discusses biopharmaceutics of nasal preparations fi om a general biopharmaceutics viewpoint. This subsection adds some more specific details, first on the nasal absorption and then on the many investigations on absorption enhancing substances. The interest for nasal absorption is predominantly raised by the desire to find an alternative administration route for systemically acting active substances. 

In short term studies cyclodextrins caused less histological changes of the nasal epithelium in rats than for instance benzalkonium chloride [24], Other studies in rats showed that dimethyl betacyclodextrin, methylated betacyclodextrin and hydroxypropylbetacyclodextrin are safe and efficient enhancers of nasal absorption [8, 25, 26], These results suggest that cyclodextrins (see also Sect. 18.1.4) can be used in nasal preparations, but more research is still needed. 

Ahsan, E., ]. ]. Arnold, E. Meezan, and D. ]. Pillion. Sucrose cocoate, a component of cosmetic preparations, enhances nasal and ocular peptide absorption. Int J Pharm 2003 251(1-2) 195-203. 

Similar experiments were carried out using sucrose esters in nasal insulin formulations (Figure 7). It was observed that tetradecanoylsucrose and tridecanoylsucrose were more effective in stimulating insulin absorption as compared with decanoyl-sucrose and dodecanoylsucrose. But—compared with TDM at concentrations of 0.03%—the sucrose esters were less effective in promoting nasal absorption [66], Sucrose cocoate (SL-40) is produced by the chemical esterification of coconut oil with sucrose it has frequently been used in cosmetic and dental preparations as an excipient. When this excipient was formulated with insulin at 0.125,0.25, and 0.5% concentrations, the associated plasma levels of insulin increased rapidly whereas there was no enhancement of insulin plasma levels when insulin in saline was admin-... 

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