Inhalation formulation

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. 

Hardy, J.G., Everard, M L., Coffiner, M., and Fossion, J., Lung deposition of a Nacystelyn metered dose inhaler formulation, J. Aerosol Med., 6 37-44 (1993). 

Table 3.5. Different issues to consider for peptide or protein inhalation formulations.

Ribavirin is contraindicated in patients with sickle cell anemia and other hemoglobinopathies because of its propensity to cause anemia. Similarly, persons with coronary disease should not use ribavirin, because anemia may cause deterioration of cardiac function. Oral ribavirin should not be given to individuals with severe renal impairment no dosage adjustment is necessary for the inhaled formulation. However, patients with hepatic impairment may require dosage adjustment. 

Johnson KA. Interfacial phenomena and phase behavior in metered-dose inhaler formulations. In Hickey AJ, ed. Inhalation Aerosols. New York Marcel Dekker, 1996 385-415. 

Crowder TM, Rosati JA, Schroeter JD, Hickey AJ, Martonen TB. Fundamental effects of particle morphology on lung delivery predictions of Stokes law and the particular relevance to dry powder inhaler formulation and development. Phanna Res 2002 19 239-245. 

Buckton G. Characterization of small changes in the physical properties of powders of significance for dry powder inhaler formulations. Adv Drug Delivery Rev 1997 26 17-27. 

Williams RO III, Brown J, Liu J. Influence of micronization method on the performance of a suspension triamcinolone acetonide pressurized metered-dose inhaler formulation. Pharm Dev Technol 1999 4(2) 167-179. 

Protein-based drugs have been formulated mainly as stable liquids or in cases where liquid stability is limiting as lyophilized dosage forms to be reconstituted with a suitable diluent prior to injection. This is because their delivery has been limited primarily to the parenteral routes of intravenous (IV), subcutaneous (SC), or intramuscular (IM) administration. There are a few drugs that have been developed for pulmonary delivery, such as rhDNase (Pulmozyme ) and an inhalable formulation of insulin (e.g., Exubra ). However, even such drugs have been formulated as either liquid or lyophilized or spray-dried powders. This chapter will focus only on excipients that are applicable to liquid and lyophilized protein formulations. 

Borgstrom L. Local versus total systemic bioavailability as a means to compare different inhaled formulations of the same substance. J Aerosol Med 1998 ll(l) 55-63. 

Fewer than 12 different excipients in MDI products have been formulated into metered aerosols. The availability of established FDA-approved excipients limits the formulator to a select few such ingredients. Table 1 lists excipients and the approximate amounts of some of these excipients that are currently used in MDIs. Metered-dose inhalers formulated with CFCs contain propellant 12, propellant 12/11, propellant 12/114, or propellant 12/114/11. These propellant... 

Schultz, R. K., Miller, N. K., Christensen, J. D. Method for evaluation of suspension characteristics relevant to metered dose inhaler formulations. Pharm Res 7(9, suppl.) 5 - S (1990). 

Several other therapeutic effects of sodium channel blockers have been suggested. Most of these stem from clinical activities of approved anticonvulsants and antiarrhythmics with sodium channel blocking activity. Beneficial effects of sodium channel blockers for the treatment of bipolar disease are suggested by clinical data with lamotrigine [63-67], phenytoin [68], topiramate [69], and carbamazepine [70,71]. In addition, clinical studies with lidocaine suggest efficacy in the treatment of tinnitus [72] and, as an inhaled formulation, in the suppression of cough [73,74]. 

Schering-Plough has developed a once-daily nasal spray formulation of momethasone furoate for the treatment and prevention of seasonal and perennial allergic rhinitis. Inhalation formulations have also been developed. Schering-Plough has developed an inhaled powder formulation for asthma maintenance treatment. 

Salbutamol is available as tablets, inhalers, nebuliser solution and intravenous injection. In the management of asthma at step 1 and 2 the inhaled formulation is the best option since it targets the drug and minimises side-effects. Oral tablets of salbutamol are rarely used and there is limited evidence of their effectiveness. 

Begat, P., Morton, D. A., Staniforth, J. N., and Price, R. (2004), The cohesive-adhesive balances in dry powder inhaler formulations I Direct quantification by atomic force microscopy, Pharm. Res., 21,1591-1597. 

El-Sabawi, D., Price, R., Edge, S., and Young, P. M. (2006), Novel temperature controlled surface dissolution of excipient particles for carrier based dry powder inhaler formulations, Drug Dev. Ind. Pharm., 32,243-251. 

Many corticosteroids undergo metabolism via CYP3A4 and are substrates of P-gp. They are used to suppress inflammation in the respiratory tract, reducing mucosal oedema and decreasing bronchial secretions. They are employed both to prevent acute exacerbations of chronic airways disease and to treat acute flare-ups. They may be subject to interactions when administered orally, but interactions with high-dose inhaled formulations are thought to occur due to steroid that is deposited in the oropharynx, swallowed and absorbed via the gastrointestinal tract. 

Mackin, L.A. Rowley, G. Fletcher, E.J. An investigation of carrier particle type, electrostatic charge and relative humidity on in-vitro drug deposition from dry powder inhaler formulations. Pharm. Sci. 1979, 3, 583-586. 

Clarke, J.G. Wicks, S.R. Earr, S.J. Surfactant mediated 42. effects in pressurized metered dose inhalers formulated as suspensions. I. Drug/surfactant interactions in a model propellant systems. Int. J. Pharm. 1993, 93, 221-231. 

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