Formulation inhaled

Sodium sulfite is used as an antioxidant in applications similar to those for sodium metabisulfite It is also an effective antimicrobial preservative, particularly against fungi at low pH (0.1% w/v of sodium sulfite is used). Sodium sulfite is used in cosmetics, food products, and pharmaceutical applications such as parenteral formulations, inhalations, oral formulations, and topical preparations. 

Higgins et aL [2] assessed the effects of three concentrations of inhaled nebulized fentanyl citrate solution given for post operative pain relief. Among the 30 studied patients, the patients inhaling a more concentrated solution of fentanyl citrate over 9 minutes showed a moderate analgesic response within 5 min of inhalation. In this study inhaled fentanyl did not prove more effective than the other parenteral formulations. Inhalation of 300 pg of fentanyl from the nebuhzer produced a peak concentration of 0.4 ng/mL at 2 min and a plateau concentration of 0.1 ng/mL at 15 min, while with inhalation of 100 pg, blood levels remained stable at 0.02 ng/mL. 

Pharmaceutical powder aerosols have more stringent requirements placed upon the formulation regarding moisture, particle size, and the valve. For metered-dose inhalers, the dispensed product must be deflvered as a spray having a relatively small (3—6 -lm) particle size so that the particles can be deposited at the proper site in the respiratory system. On the other hand, topical powders must be formulated to minimize the number of particles in the 3—6-p.m range because of the adverse effects on the body if these materials are accidently inhaled. 

Improvements in asthma treatment include the development of more effective, safer formulations of known dmgs. The aerosol adrninistration of P2-agonists or corticosteroids results in a decrease in side effects. Also, the use of reUable sustained release formulations has revolutionized the use of oral xanthines which have a very narrow therapeutic index (see Controlled release technology). For many individuals, asthma symptoms tend to worsen at night and the inhaled bronchodilatots do not usually last through an entire night s sleep (26,27). 

Formulation(s) cps. for inhalation 12 jig (as fumarate dihydrate) powder inhaler 6 pg/puff, 12 pg/puff... 

Formulation(s) aerosol inhalation 20 fig/metered inhalation, 40 pg/metered inhalation inhalation sol. 250 pg/... 

In a case-control study of pesticide factory workers in Brazil exposed to methyl parathion and formulating solvents, the incidence of chromosomal aberrations in lymphocytes was investigated (De Cassia Stocco et al. 1982). Though dichlorodiphenyltrichloroethane (DDT) was coformulated with methyl parathion, blood DDT levels in the methyl parathion-examined workers and "nonexposed" workers were not significantly different. These workers were presumably exposed to methyl parathion via both inhalation and dermal routes however, a dose level was not reported. The exposed workers showed blood cholinesterase depressions between 50 and 75%. However, the baseline blood cholinesterase levels in nonexposed workers were not reported. No increases in the percentage of lymphocytes with chromosome breaks were found in 15 of these workers who were exposed to methyl parathion from 1 week to up to 7 years as compared with controls. The controls consisted of 13 men who had not been occupationally exposed to any chemical and were of comparable age and socioeconomic level. This study is limited because of concomitant exposure to formulating solvents, the recent history of exposure for the workers was not reported, the selection of the control group was not described adequately, and the sample size was limited. 

Two neuraminidase inhibitors (oseltamivir carboxylate and zanamivir) are approved for prevention and treatment of infections with both influenza A and B viruses as discussed in chapter by Itzstein and Thomson, this volume. Oseltamivir carboxylate (OC) has gained most use because it can be taken orally, whereas the current formulation of zanamivir has to be inhaled. In addition, the WHO reconunends oseltamivir for treatment of clinically confirmed cases of H5N1 and for post-exposme prophylaxis to control recent H5N1 avian influenza outbreaks. 

In occupational settings, exposure to endosulfan is mainly via the dermal and inhalation routes. Although workers involved in the manufacture and formulation of pesticide products containing endosulfan are potentially exposed to high concentrations of the compound, actual exposure is probably limited by the use of engineering controls and personal protection equipment. The highest documented dermal and inhalation exposures have been reported for agricultural workers involved in the spray... 

In light of the information presented, it appears that liposomes have much to offer as an improved delivery system for inhaled bronchodilators as they can provide sustained release, solubilization, stability, and safety in an inhalable formulation. 

Fielding, B. (1989). Drug delivery to the lungs and systemic circulation by inhalation of liposome based formulations, in Proc. 32nd Annual Meeting Western Pharmacology Society. Brecken-ridge, Colorado, January 1989. In Press. 

Besides the inhalative use, the development of a drug formulation for A9-THC has to address other bioavailabihty questions. A major problem is the hpophiUcity and poor solubiUty in water, hmiting oral uptake when given orally. Because of this, other parenteral routes of apphcation are imder investigation like puhnonal uptake by vaporization, subUngual or intranasal administration, and apphcation by injection of A9-THC incorporated in hpo-somes. 

Applicators, mixers, loaders, and others who mix, spray, or apply pesticides to crops face potential dermal and/or inhalation exposure when handling bulk quantities of the formulated active ingredients. Although the exposure periods are short and occur only a few times annually, an estimate of this exposure can be obtained by quantifying the excreted polar urinary metabolites. Atrazine is the most studied triazine for potential human exposure purposes, and, therefore, most of the reported methods address the determination of atrazine or atrazine and its metabolites in urine. To a lesser extent, methods are also reported for the analysis of atrazine in blood plasma and serum. 

Nebulized colistin using the IV formulation may be an option in patients with tobramycin-resistant strains or intolerance to inhaled tobramycin. Due to an increased risk of bronchoconstriction after colistin inhalation, patients should pre-treat with albuterol and administer the first doses under medical observation.1,5... 

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