Absorption nasal mucosa

Inhalation (IH) The administration of volatile gases and vapours, followed by drug absorption in the lungs or nasal mucosa. Examples include general anaesthetics like nitrous oxide, nicotine from the tar droplets in tobacco smoke, cannabinoids from cannabis leaf smoke and various opiates from burning opium resin. 

Topical decongestants are applied directly to swollen nasal mucosa via drops or sprays (Table 79-3). They result in little or no systemic absorption. 

In addition to peptide-based studies, degradation and absorption kinetics of a homologous series of acyclovir ester prodrugs have been studied using the in situ perfusion model [25, 26], The studies showed that due to high esterase activity of the rat nasal mucosa (96% disappearance of hexanoate prodrug of acyclovir in 960 min), the rat in situ model is an acceptable model to screen the nasal absorption of prodrugs. 

Wadell C, Bjork E, Camber O (2003) Permeability of porcine nasal mucosa correlated with human nasal absorption. Eur J Pharm Sci 18 47-53. 

Wang J, Sakai S, Deguchi Y, Bi D, Tabata Y, Morimoto K (2002) Aminated gelatin as a nasal absorption enhancer for peptide drugs evaluation of absorption enhancing effect and nasal mucosa perturbation in rats. J Pharm Pharmacol 54 181— 188. 

This refers to the transport across the epithelial cells, which can occur by passive diffusion, carrier-mediated transport, and/or endocytic processes (e.g., transcytosis). Traditionally, the transcellular route of nasal mucosa has been simply viewed as primarily crossing the lipoidal barrier, in which the absorption of a drug is determined by the magnitude of its partition coefficient and molecular size. However, several investigators have reported the lack of linear correlation between penetrant lipophilicity and permeability [9], which implies that cell membranes of nasal epithelium cannot be regarded as a simple lipoidal barrier. Recently, compounds whose transport could not be fully explained by passive simple diffusion have been investigated to test if they could be utilized as specific substrates for various transporters which have been identified in the... 

The existence of a carrier-mediated transport in nasal mucosa was first suggested by Kimura et al. [34], P-glycoprotein, organic cation transporter, dopamine transporter, and amino acid transporters have all been identified in the nasal mucosa, especially in the olfactory mucosa [31, 32, 35, 36], These transporters determine the polarized absorption and excretion of their substrates including amino acids, amines, and cations. 

Ilium et al. [49] evaluated chitosan solutions as delivery platforms for nasal administration of insulin to rats and sheep. They reported a concentration-dependent absorption-enhancing effect with minimal histological changes of the nasal mucosa in all concentrations applied. 

The difficulty with HLB as an index of physicochemical properties is that it is not a unique value, as the data of Zaslavsky et al. (1) on the haemolytic activity of three alkyl mercaptan polyoxyethylene derivatives clearly show in Table 1. Nevertheless data on promotion of the absorption of drugs by series of nonionic surfactants, when plotted as a function of HLB do show patterns of behaviour which can assist in pin-pointing the necessary lipophilicity required for optimal biological activity. It is evident however, that structural specificity plays a part in interactions of nonionic surfactants with biomembranes as shown in Table 1. It is reasonable to assume that membranes with different lipophilicities will"require" surfactants of different HLB to achieve penetration and fluidization one of the difficulties in discerning this optimal value of HLB resides in the problems of analysis of data in the literature. For example, Hirai et al. (8 ) examined the effect of a large series of alkyl polyoxyethylene ethers (C4,C0, Cj2 and C 2 series) on the absorption of insulin through the nasal mucosa of rats. Some results are shown in Table II. 

Stabilization of mast cells. Cromolyn prevents IgE-mediated release of mediators, although only after chronic treatment. Moreover, by interfering with the actions of mediator substances on inflammatory cells, it causes a more general inhibition of allergic inflammation. It is applied locally to conjunctiva, nasal mucosa, bronchial tree (inhalation), intestinal mucosa (absorption almost nil with oral intake). Indications prophylaxis of hay fever, allergic asthma, and food allergies. 

Pharmacokinetics Onset of action is about 10 min and duration of action is 7 hr or more. Absorption occurs from the nasal mucosa and can produce systemic effects, primarily following overdose or excessive use. Excreted mostly in the urine as well as the feces. Half-life 5-8 hr. 

Also in the case of nasal IT, no direct absorption through the nasal mucosa could be detected [52]. The allergen sprayed into the nose is slowly transported towards the pharynx by the mucociliary clearance and then swallowed, although a relevant fraction persists on the nasal mucosa for hours. 

The nasal epithelium possesses selective absorption characteristics similar to those of a semipermeable membrane, i.e., it allows a rapid passage of some compounds while preventing the passage of others. The process of transportation across the nasal mucosa involves either passive diffusion, via paracellular or transcellular mechanisms, or occurs via active processes mediated by membrane-bound carriers or membrane-derived vesicles involving endo- or transcytosis. 

Drug permeability, metabolism, and toxicity can be evaluated in vitro using models of the nasal epithelial in preparation for in vivo experiments. Human nasal epithelial cell cultures and animal nasal mucosa mounted in Ussing chambers provide convenient, simple systems in which drug targeting and absorption mechanisms can be investigated under defined, controlled conditions [45],... 

Hirai, S., et al. 1981. Absorption of drugs from the nasal mucosa of rats. Int J Pharm 7 317. 

Calcitonin is a peptide hormone produced in the thyroid gland that serves to lower serum calcium and phosphate levels by inhibiting bone resorption. Calcitonin has been used in the treatment of a variety of diseases, such as primary hyperparathyroidism, Paget s disease, and postmenopausal osteoporosis [99,100]. Salmon calcitonin has a longer half-life than human calcitonin. Salmon calcitonin, 3.6 kDa, is available as a nasal formulation that contains only benzalkonium chloride as a preservative, without an absorption enhancer, and as a parenteral product for injection. The direct effect of benzalkonium chloride on the nasal mucosa is under... 

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