In nasal formulations

The most serious adverse reaction to mineral oil is lipoid pneumonia caused by aspiration of the oil. Mineral oil can enter the bronchial tree without eliciting the cough reflex.With the reduction in the use of mineral oil in nasal formulations, the incidence of lipoid pneumonia has been greatly reduced. However, lipoid pneumonia has also been associated with the use of mineral oil-containing cosmetics and ophthalmic preparations. It is recommended that products containing mineral oil not be used in very young children, the elderly, or persons with debilitating illnesses. 

Penetration enhancers are often used to improve peptide bioavailability in nasal formulations. A variety of different enhancers have been tried, and they work by one or several combined mechanisms. Some act by increasing the membrane fluidity and reducing the viscosity of the mucus layer, thereby increasing membrane permeability. Others act by transient loosening of the tight junctions between epithelial cells. The types of penetration enhancers discussed in the research literature include the following. 

Benzalkonium chloride is so far the most widely used preservative, but thiomersal, chlorobutanol, phenylethanol, and parabens can also be found in nasal formulations. 

Fig. 17.13. Electropherograms obtained for the analysis of a nasal formulation for the determinations of benzalkonium chloride (BC) in the presence of active pharmaceutical ingredient (R91274) and other placebo ingredients. Conditions 75 mM sodium phosphate buffer, pH = 2.3, 35 cm fused silica capillary (effective length 28.5 cm) x 75 pm I.D., injection 10 s at 35mbar, 20°C, 15 kV (positive polarity) resulting in a current of approximately 95 pA, detection UV 215 nm.

Nasal formulations of modern sympathicomimet-ics like oxymetazoline and xylometazoline are effective. Rebound nasal congestion after withdrawal of sympathicomimetic-containing nose sprays or drops is a common phenomenon and patients should be advised to use these medicaments no longer than 3-5 days. Older per oral drugs like ephedrine and pseudo-ephedrine have no place in the therapy of rhinitis due to the risk of serious adverse reactions which are not in proportion to the indication. 

Ethylene glycols Formulation aid for nasal delivery Single and repeat-dose nasal toxicity (up to 14 days— intranasal rabbit) Mild local toxicity likely to be acceptable in clinical nasal formulations for short-term use 35... 

Solution-based systems are common to both nebulizers and nasal formulations. In general, water will form the greatest fraction of the formulation, but, in some cases, cosolvents such as ethanol and propylene glycol may be added for increased stability. Acidifying and alkalizing excipients may also be added to optimize pH from the perspective of the drug stability as well as the physiological effect on the airways. Similarly, iso-osmotic and iso-tonic solutions are preferred. 

Major determinants of the efficiency of mucociliary clearance are cilia density, periciliary fluid, and composition of mucus. Some drugs and excipients, such as preservatives in drug formulations, may diminish the ciliary movement in the nasal cavity and trachea. A suggested adverse effect of ciliostasis (permanently or momentarily arrest or impairment of ciliary activity) is lower respiratory tract infection as a result of impaired nasal microbiological defense. 

Chitosan is a cationic polysaccharide produced from the deacetylation of chitin, a component of crab and shrimp shells [7,57,58], Chitin is composed of units of 2-deoxy-2-(acetylamino) glucose joined by glycosidic bonds that form a linear polymer. Ilium et al. [7,57,58] demonstrated the ability of chitosan to increase the bioavailability of insulin and other small peptides and polar macromolecules in different animal models. In both the sheep and rat models, the addition of chitosan at concentrations of 0.2%-0.5% to nasal formulations of insulin resulted in significant increases in plasma insulin and reductions in blood glucose. Reversibility studies indicated that the effect of chitosan on the nasal absorption of insulin... 

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... 

---