Nasal drug absorption application

Fig. 4 Variable factors influencing nasal drug absorption, and related key points for practical application.

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],... 

In Fig. 3, a standard experimental system in rats is shown. Drug solutions of 3-20 mL are continuously circulated through the nasal cavity of anesthesized rats, whereas the drug concentration in the solution is periodically determined by standard analytical procedures. The obtained disappearance kinetics can be used for predicting the in vivo rate of drug absorption. The method is also applicable to the assessment of the damaging effects of absorption enhancers on the nasal mucosa. 

The nasal application of drugs is an area of growing interest (21) and a number of publications has shown that simple molecules as well as more complex species (eg calcitonin, insulin etc) can be well absorbed by this route, either directly or in the presence of so-called absorption enhancers. One problem with such materials could be too rapid clearance of the delivery system from the nasal cavity through the efficient action of the mucociliary system. For this reason Ilium has considered the use of microsphere systems. 

It has been shown in a number of studies that the incorporation of drug in o/w nanosized emulsions significantly increased the absorption of the drug when compared with the equivalent aqueous solution administered orally [132-135], However, the use of emulsions for oral application is limited since other attractive alternatives, such as self-emulsifying oil delivery systems, which are much less sensitive and easy to manufacture, are available [136,137], Thus the potential of nanosized emulsions after administration with parenteral and traditional nonparenteral topical routes such as ocular, percutaneous, and nasal is covered in this section. 

All routes of drug administration can affect ocular structures and functions. OADRs have been associated with topical ophthalmic administrations as well as local injections. Systemically, oral drug administration has been implicated most frequently in the development of OADRs. However, parenteral as well as inhaled or nasally applied drugs have also produced OADRs. Topical application to the skin, particularly if it is abraded or burned, may result in sufficient systemic absorption to lead to ocular side effects. Dermatologic use of antibiotics has resulted in ocular hypersensitivity reactions. 

The lack of activity after oral administration for most peptides and proteins resulted in the past besides parenteral application into the utilization of nonoral administration pathways, for example, nasal, buccal, rectal, vaginal, percutaneous, ocular, or pulmonary drug delivery [27]. Drug delivery via these administration routes, however, is also frequently accompanied by presystemic degradation processes. Bioavailability of numerous peptides and proteins is, for example, markedly reduced after subcutaneous or intramuscular administration compared to their intravenous administration. The pharma-cokinetically derived apparent absorption rate constant is thus the combination of absorption into the systemic circulation and presystemic degradation at the absorption... 

Factors limiting the drug uptake after nasal application are the limited absorption area of 160 cm and the short contact time of 20 min due to cilliaric transport (sa). Furthermore, there are proteases and peptidases located in the mucus of the nasal tissue, however, at concentrations that are easily saturable in many cases. 

Medicinal products administered at a specific site to obtain a local effect should preferably not be absorbed systemically. However, significant amounts of active substance can be absorbed, e.g. after application on the skin. Removal of locally acting active substances from the site of action by systemic absorption may result in systemic effects that can be considered as adverse effects. After nasal, ocular, pulmonary and rectal administration of active substances for a local effect, absorption into the systemic circulation is likely to occur. This may cause adverse effects and limit the duration of the desired drug effect. Conversely it should be realised that the systemic route is often also the main route for clearance of the active substance from the site of administration. The bioavaUability of locally acting medicines is, of course, not determined by the amount of active substance that reaches the systemic circulation. As an alternative the fraction of the active substance that is dissolved in the aqueous fluids at the site of application is usually taken as a measure for the bioavailability. 

A lipid system of biosomes composed of PC from soybean and medium-chain mono-acylglycerol and low-molecular-weight heparin (LMWH), used in the treatment and prevention of thromboses, was reported (56). Heparin is known as having poor oral absorption. The system is applicable for oral and parentral administration as well as for enhancing dermal, rectal, and nasal absorption of other drugs. 

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