Excipient powder aerosol formulations

Although excipients are the non-active ingredients, they are indispensable for the successful production of acceptable solid dosage forms. The important roles played by excipients in tablets and capsules, freeze-dried, and spray-dried powders, as well as powder aerosol formulations, were discussed. Some recent applications of excipients in controlled, release formulations for biologicals were also highlighted. Finally, incompatibility problems attributable to excipients were considered with an emphasis on the indirect role of excipients through moisture distribution. 

Such small particles usually are generated by air-jet micronization and less frequently by controlled precipitation or spray drying. As bulk powder, they usually tend to be very cohesive and exhibit poor flow and insufficient dispersion because of large interparticle forces such as van der Waals and electrostatic forces (Zeng et al. 2001 Podczeck 1998 Hickey et al. 1994). The control of sufficient powder flow and deaggregation (dispersion) is thus of utmost importance to ensure efficient therapy with a dry-powder aerosol. Two different formulation approaches are used currently in marketed DPI preparations to fulfill the requirements. Most often, coarse particles of a pharmacologically inactive excipient, usually a-lactose monohydrate, are added that act as a carrier and provide sufficient powder flow to the mixture. Other carbohydrates, amino acids, and phospholipids have been suggested frequently (Crowder et al. 2001). 

The physical properties of the solid state seen in crystals and powders of both drugs and pharmaceutical excipients are of interest because they can affect both the production of dosage forms and the performance of the finished product. Powders, as Pilpel reminded us, can float like a gas or flow like a liquid but when compressed can support a weight. Fine powders dispersed as suspensions in liquids are used in injections and aerosol formulations. Both liquid and dry powder aerosols are available and are discussed in Chapter 9 some properties of compacted solids are dealt with in Chapter 6. In this chapter we deal with the form and particle size of crystalline and amorphous drugs and the effect these characteristics have on drug behaviour, especially on drug dissolution and bioavailability. 

Andya, J.D. Maa, Y.F. Constantino, H.R. Nguyen, P.A. Dosovich, N. Sweeny, T.D. Hsu, C.C. Shire, S.J. The effect of formulation excipients on protein stability and aerosol performance of spray-dried powders of recombinant humanized anti-IgE monoclonal antibody. Pharm. Res. 1999, 16, 350-358. 

In aerosols, other than those for inhalation, colloidal silicon dioxide is used to promote particulate suspension, eliminate hard settling, and minimize the clogging of spray nozzles. Colloidal silicon dioxide is also used as a tablet disintegrant and as an adsorbent dispersing agent for liquids in powders. Colloidal silicon dioxide is frequently added to suppository formulations containing lipophilic excipients to increase... 

Bosquillon C, Lombry C, Preat V, Vanbever R. Influence of formulation excipients and physical characteristics of inhalation dry powders on their aerosolization performance. J Control Release 2001 70 329-39. 

The delivery of aerosol powders by generation with minimal formulation has been an attractive prospect to many researchers. The early use of a dry powder artificial phospholipid in the treatment of neonatal respiratory distress syndrome proved very successful [181]. Because no delivery system was available to facilitate this treatment, a simple system was devised. A Laerdal neonatal resuscitation bag was modified to hold a capsule containing the artificial surfactant, as shown schematically in Fig. 11. However, where MDIs of the prescribed medication are available, both physicians and patients prefer their use. The powders themselves have to be prepared in the same way as those used in MDIs, by milling. Often, excipients are added to carry the fine powder. Lactose has been used in both cromolyn sodium and albuterol formulations. As a consequence of the interest in dry powders, a number of products have been... 

The effect of processing technique on the aerosol performance of insulin formulations prepared by DG antisolvent precipitation and spray drying has been investigated. Two types of insulin formulations were produced. They were 1 20 insulin-mannitol (IM) and 1 20 8 insulin-mannitol-citric acid (IMC). Mannitol is an excipient commonly used to improve aerodynamic performance of powders for inhalation delivery. Citric acid has been found effective in improving insulin absorption in the lungs. ... 

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