Nasal dosage forms

Uses W/o emulsifier, emulsion stabilizer, bioavailabilily enhancer in penetration aid in topical formulations used in tablets, periodontal dmg delivery fems, nasal dosage forms... 

The use of a bioadhesive, polymeric dosage form for sustained dehvery raises questions about swallowing or aspirating the device. The surface area is small, and patient comfort should be addressed by designing a small (less than 2 cm ), thin (less than 0.1 mm (4 mil) thick) device that conforms to the mucosal surface. The buccal route may prove useful for peptide or protein dehvery because of the absence of protease activity in the sahva. However, the epithelium is relatively tight, based on its electrophysiological properties. An average conductance in the dog is 1 mS/cm (57) as compared to conductances of about 27 and 10 mS/cm in the small intestine and nasal mucosa, respectively (58,59) these may be classified as leaky epitheha. 

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. 

Solid dosage forms based on mucoadhesive polymers are used mainly for buccal delivery of drugs, whereas micro- or nanoparticulate formulations are preferred for the delivery of therapeutics in the nasal and intestinal tract [5]. 

Nakamura et al. [54] deseribe a mieropartieulate dosage form of budesonide, consisting of novel bioadhesive and pH-dependent graft copolymers of polymethacrylic acid and polyethylene glycol, resulting in elevated and constant plasma levels of budesonide for 8 hr after nasal administration in rabbits. 

The inclusion of the a routine microbial limit test in a marketed product stability protocol depends on the pharmaceutical dosage form. Typically, the test would be used only for nonsterile products, especially oral liquids, nasal sprays, and topical liquids, lotions, and creams that have sufficient water activity to support the growth of microorganisms. In contrast, tablets, powder- and liquid-filled capsules, topical ointments, vaginal and rectal suppositories, nonaqueous liquids and inhalation aerosols with a water activity too low to allow for the product to support the growth of microorganisms would not be routinely tested. 

Dosage Forms for Oral, Ocular, and Nasal Applications... 

Dosage form Two versions of Synarel are available Synarel Nasal Solution for Central Precocious Puberty and Synarel Nasal Solution for Endometriosis. They appear to be the same except for package and labeling. Each 0.5 ounce bottle contains 8 ml Synarel Nasal Solution 2mg/ml (as nafarelin base). Each bottle is supplied with a metered spray pump that delivers 200 pg of nafarelin per spray. 

The major limitation to developing therapeutic proteins in nonparenteral dosage forms is the poor permeability of these water-soluble and hygroscopic macromolecules across the tissue layers at the site of drug administration. These tissue layers include the epithelium of the gastrointestinal tract, the stratum corneum of the skin, and the epithelium lining of the alveoli and nasal cavity. 

In the general chapter on microbial attributes of nonsterile pharmaceutical products, the guidance suggests that the presence of microbial contaminants in nonsterile products [25] can reduce or inactivate the therapeutic activity of the product and has the potential to adversely effect the health of the patients and recommends manufacturers to ensure that contamination levels are as low as possible for finished dosage forms. Microbial enumeration limits for raw materials (total aerobic microbial count and total combined yeasts and molds count) and finished dosage forms are described. For inhalation, nasal, and topical routes of administration, tests for total aerobic microbial count and total combined and yeast and mold count,... 

Inhalation drug products include inhalation aerosols (metered dose inhalers) inhalation solutions, suspensions, and sprays (administered via nebulizers) inhalation powders (dry powder inhalers) and nasal sprays. The CMC and preclinical considerations for inhalation drug products are unique in that these drug products are intended for respiratory tract-compromised patients. This is reflected in the level of concern given to the nature of the packaging components that may come in contact with the dosage form or the patient. 

Certain kinds of improvements are possible in almost every dosage form. Besides oral and injectable formulations, CD inclusion has been shown to improve bioavailability of compounds administered by other routes, including ocular, topical, nasal, and rectal routes (Uekama et al., 1994 Marttin et al., 1998 Bary et al., 2001 Loftsson and Masson, 2001 Rode et al., 2003). Some important applications particularly applicable for insoluble compounds are summarized below. 

Nagai, T., and Y. Machida. 1990. Bioadhesive dosage forms for nasal administration, in Bioadhesive drug delivery systems, eds. V. Lenearts, and R. Gurny, 169. Florida CRC Press, chap. 9. 

Nagai, T., et al. 1984. Powder dosage form of insulin for nasal administration. J Control Release 1 15. 

Ando, T., et al. 1998. Nasal insulin delivery in rabbits using soybean-derived sterylglucoside and sterol mixtures as novel enhancers in suspension dosage forms. Biol Pharm Bull 21 862. 

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