Solutions nasal formulations

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. 

Since the introduction of metered-dose inhalers, nasal solutions have increasingly been formulated as nasal sprays. Initially, aerosol-based systems containing chloro-fluorocarbons were employed however, the Montreal Protocol put an end to this. Thereafter, mechanical pumps or actuators were employed to deliver nasal formulations as sprays. These devices, using actuators, can precisely deliver as little as 25 pL and as much as 200 pL of a formulation. However, various factors must be considered in formulating the spray these include viscosity, particle size, and surface tension, all of which may affect the accuracy of the dose administered. 

Diazepam As mentioned earlier, because of shortcomings of rectal administration, the nasal delivery of diazepam has gained interest. The nasal bioavailability of diazepam in sheep was estimated and further compared with results obtained earlier in humans and rabbits [106] in this study, human and rabbit nasal bioavailability for the first 30min was reported to be 37 and 54%, respectively [113]. Diazepam solubilized in PEG 300 was used for nasal administration via a modified nasal device, a Pfeiffer unit dose (Princeton, NJ). The sheep received the nasal formulations in a fixed standing position such that the head was slightly tilted back. It was found that the serum concentration after administration of a 7-mg solution of diazepam was... 

Solutions, nasal Solutions of drugs for instilling in the nose rather than spraying are generally a modern development. The first nasal solutions were formulated with menthol and thymol dissolved in light mineral oil. Later isotonic aqueous solutions were designed as drops. ... 

The route of administration depends on the disease being treated and the physicochemical, pharmacologic, and pharmacokinetic properties of the drug (Table 33.1). The clinically available adrenocorticoids may be administered by IV injection, oral tablets or solutions, topical formulations, intra-articular administration, and oral or nasal inhalation (Table 33.2). Only a handful of... 

Numerous reports concerning the stability of neomycin in various dosage forms have been published. Simone and Popino298 studied the stability of neomycin in liquid dosage forms such as nasal drops, mouth washes and tinctures. The antibiotic was stable in all the formulations tested, except Dobells solution (a mouth wash), for at least 6 months at 20°C. Some formulations were stable for considerably longer. 

Additional factors influencing nasal peptide absorption include particle residence time and formulation pH and osmolarity. Ohwaki et al (10) measured the effect of solution pH and osmolarity on the intranasal absorption of secretin, a 27 amino acid peptide, in rats. Nasal secretin absorption, as measured by pancreatic secretion rates, was maximal at a formulation pH of 3.0 almost eight times greater than at neutral pH. Solution osmolarity had less effect overall on secretin absorption, maximal absorption occurring in a hyperosmolar saline solution of 0.462 M. 

Drags to be administered to the nasal cavity are generally formulated as nasal drops, which deposit a film of drag solution, or nasal sprays which deposit an aerosol of particles, droplets or particles suspended in droplets. For absorption of aerosol formulations, deposition of the aerosol must occur followed by dissolution of solid particles if applicable. 

Increasing the viscosity of solutions administered to the nasal cavity with, for example, methylcellulose, hyaluronan etc., has been shown to increase the time the formulation is retained in the nasal cavity and to enhance the absorption of certain drugs. It is thought that, up to an optimum viscosity, higher viscosity solutions give a more localized deposition in the anterior portion of the nose (i.e. low clearance site). As viscosity can affect droplet size by altering the surface tension of the solution, the more localized deposition in the anterior of the nose may be due to viscosity-related changes in the particle size of the delivered droplets. 

Topical dosage forms such as creams, emulsions, gels, lotions, ointments, pastes, and powders may be marketed in plastic materials. Topical dosage formulations are for local (not systemic) effect and are generally applied to the skin or oral mucosal surfaces. Some vaginal and rectal creams and nasal, otic, and ophthalmic solutions may be considered for topical drug products. 

Both the type of drug delivery system and the specific type of delivery device can affect drug absorption via the nasal route. The choice of delivery system depends mainly on the physiochemical properties of the drug, its desired site of action, and, more importantly, patient compliance and marketing aspects. The formulations most commonly used in nasal delivery are solutions, suspensions, gels, dry powders, and, most recently, nanoparticulate formulations. 

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