Formulations nasal products

Hodges NA, Denyer SP, Hanlon GW, Reynolds JP. Preservative efficacy tests on formulated nasal products reproducibility and factors affecting preservative activity. ] Pharm Pharmacol 1996 48 1237-1242. 

Since a comprehensive listing of every potential peptide and macromolecule that could be delivered nasally is not possible, this section will focus on (1) the drugs currently in use as nasal products in humans, (2) drugs currently in use as injectables in humans that will gain increased utilization if and when they can be formulated for nasal delivery, and (3) drugs that are currently in development for utilization in humans (Table 20.2). 

Many of the points raised in this section have been mentioned in the earlier sections on formulation and device. A Guidance for Industry document in draft form was issued by the FDA during 1999, Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products Chemistry, Manufacturing and Controls Documentation (FDA 1999). This document provides a plethora of information on issues the FDA will consider in submitted documentation supporting the approval of nasal products. There are over 1,600 lines in the document, and industry comments have been invited. Whilst the final document has yet to be issued, the draft is still an important reference. A brief review of the content of this draft document follows. 

A range of nasal peptides such as desmopressin, buserelin, nafarelin and oxytocin, have been formulated into licensed nasal products. However, none of them contains a nasal absorption enhancer. Even though these nasal products are characterised by low peptide bioavailability they are efficacious, as low systemic levels are needed to exert a therapeutic effect. However, developing of novel safe and efficient nasal absorption enhancers is of great interest to improve bioavailability of presently marketed peptides and to provide sufficient nasal permeability of less potent biologicals [22]. 

For nebulizer and other aqueous aerosol products that use suspension systems, excipients are used to influence particle physical and chemical stability (e.g., microcrystalline cellulose for nasal sprays). The suitability of the physicochemical properties of these critical excipients should be thoroughly investigated and documented (12). Far more excipients have been included in formulations designed for nasal administration (Table 4). 

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... 

Several peptide products used in the treatment of diabetes mellitus, in addition to insulin, are currently administered by subcutaneous injection and these drugs are candidates for development of nasal formulations. Glucagon-like peptide-1 (GLP-l)-related peptides stimulate the insulin response to glucose and diminish the release of glucagon after a meal. These effects diminish the excessive postprandial increase in glucose observed after a meal in persons with type 2 diabetes mellitus. GLP-1-related peptides must be administered by subcutaneous injection before meals in order to be effective. This requirement for injection before each meal is likely to impact the utilization of these products by persons with type 2 diabetes. Exendin-4 is a GLP-1-related peptide with a molecular mass of 4.2 kDa. The development of a GLP-1-related peptide nasal formulation containing an absorption enhancer would allow patients to scll-administer one of these drugs just before a meal without the need for a subcutaneous injection. 

Epoetin alfa, recombinant erythropoietin, is a glycoprotein that simulates erythrocyte production. Epoetin alfa is administered three times weekly subcutaneously or intravenously. Epoetin is used to treat anemia in patients with chronic renal failure, HIV infection, and patients receiving chemotherapy [104]. Development of a safe, effective nasal formulation of epoetin alfa, containing an absorption enhancer could once again improve the efficacy of epoetin alfa therapy, and reduce the number of injections required in these sensitive patient populations. 

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. 

To get a better idea of how to formulate the nanosized emulsion delivery systems suitable for parenteral, ocular, percutaneous, and nasal uses, the reader is referred to more detailed descriptions of methods of nanosized emulsion preparation [6, 116], A hot-stage high-pressure homogenization technique or combined emulsification technique (de novo production) is frequently employed in order to prepare nanosized emulsions with desired stability even after subjection to autoclave sterilization. Therefore, the steps involved in this technique in making blank anionic and cationic emulsions were arranged in the following order ... 

Pesticide poisoning has become common among farm workers, pesticide applicators, mixers, loaders, and handlers. This has been traced to the users ignorance, carelessness, and lack of elementary knowledge about taking the proper precautions before handling toxic chemicals. The symptoms of pesticide poisoning are not common to all the products, but vary with each product and its formulation. Some of the symptoms include headache, nausea, muscle aches, irritation of eyes and nasal and... 

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