Nasal preparations

Intal, Nasalcrom Prophylaxis of severe bronchial asthma prevention of exercise-induced asthma (BA) Nasal preparations prevention and treatment of allergic rhinitis Dizziness, headache, nausea, dry and irritated throat, rash, joint swelling and pain... 

The provision of optimal drug action from topical administration sites (such as ointments, creams, transdermal patches, ophthalmic, ear, and nasal preparations)... 

Do not use nasal preparations for >3-5 days to prevent rebound congestion... 

If disturbances of gastrointestinal function prevent the use of oral sustained-release morphine, the fentanyl transdermal system (fentanyl patch) can be used over long periods. Furthermore, buccal transmucosal fentanyl can be used for short episodes of breakthrough pain (see Alternative Routes of Administration). Administration of strong opioids by nasal insufflation has been shown to be efficacious, and nasal preparations are now available in some countries. Approval of such formulations in the USA is growing. In addition, stimulant drugs such as the amphetamines have been shown to enhance the analgesic actions of the opioids and thus may be very useful adjuncts in the patient with chronic pain. 

Nafarelin is available as Synarel, a nasal preparation. The head should be tilted back and 30 seconds allowed to elapse between each spray. Nafarelin is rapidly absorbed by the nasal mucosa. Maximum serum levels occur in 10-40 minutes. Rhinitis is a common side effect. Sneezing should be avoided after administration. Nasal decongestants must not be used for 2 hours following each dose. 

GRAS listed. Accepted for use in Europe as a food additive. Included in the FDA Inactive Ingredients Guide (aerosol formulation for nasal preparations IM and IV injections). Included in the Canadian List of Acceptable Non-medicinal Ingredients. 

Sensitization reactions may follow the prolonged application of strong solutions to the skin, although patch tests have shown that chlorocresol is not a primary irritant at concentrations up to 0.2%. Cross sensitization with the related preservative chloroxylenol has also been reported. " "" At concentrations of 0.005% w/v, chlorocresol has been shown to produce a reversible reduction in the ciliary movement of human nasal epithelial cells in vitro and at concentrations of 0.1% chlorocresol produces irreversible ciliostasis therefore it should be used with caution in nasal preparations. " However, a clinical study in asthma patients challenged with chlorocresol or saline concluded that preservative might be used safely in nebulizer solution. ... 

Nasal preparations contain anti-inflammatory, sympathomimetic decongestant or... 

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. 

Batts, A. H., C. Marriott, G. P. Martin, and S. W. Bond. 1989. The effect of some preservatives used in nasal preparations on mucociliary clearance./. Pharm. Pharmacol. 41 156-159. 

Drugs are frequendy applied topically to the eye, ear, and mucus membranes of the nose. In these instances ointments, suspensions, and solutions are generally employed. They are generally not employed for systemic effects. Nasal preparations may be absorbed and a systemic effect may be seen. 

Nasal preparations are usually solutions or suspensions administered by drops or as a fine mist from a nasal spray container, which could include an aerosol with a metered valve. 

This chapter deals with preparations for nasal administration, with a local or a systemic effect. Classical nasal preparations were always associated with local ailments, but nowadays the interest in the nasal route for systemi-cally acting substances and direct nose to brain delivery is increasing. Fast absorption, the possibility of high blood levels and a patient friendly dosage form are the reasons. Nasal administration of medicines with local effect is the first choice for the treatment of topical nasal disorders. It is also an attractive route for low dose active substances with a systemic effect, such as peptides or benzodiazepines (e.g. midazolam). When compared to parenteral administration nasal administration is more easily applied and causes less risk of infection. 

Nasal preparations can be formulated as liquid, semisolid or solid preparations and can contain one or more active substances. Whether intended for local or systemic action, the mucociliary function of the nose should be disturbed as httle as possible by the preparation However, it is well known that active substances as weU as excipients may have a negative influence on the mucociliary clearance, in other words may be cdiotoxic. In the formulation of nasal preparations one should take into consideration the possible damage to the cilia in relation to the indication and the period of use. 

Ciliotoxic Mucociliary clearance Nasal preparation Local effect Systemic effect Preparation Formulation... 

Active substances formulated as nasal preparations are traditionally used in the treatment of local ailments such as allergy, congestion and infections. Nasal preparations that are prepared in the pharmacy are mainly intended for the inner part of the nose. In addition nasal drops are often applied in diseases of the middle ear, in order to keep the Eustachian tube open (see Sect. 9.1). 

Examples of nasal preparations with local action are given in Table 8.1. 

Table 8.1 Nasal preparations with local action (examples)...

Generally speaking active substances with a systemic therapeutic action can be formulated as nasal preparations under the following conditions high water-solubUity (required dose must fit in 25-150 microlitres vehicle), sufficient chemical stability, no unpleasant smell or taste, favourable nasal absorption parameters, minimal nasal irritation and clinically important properties such as fast onset of therapeutic action, low dosage (normally less than 25 mg per dose), and no toxic metabolites [3, 8]. 

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