Insulin inhalation spray

In the not too distant future, Insulin intake will become even easier. Thanks to a new insulin inhaler, by Generex, insulin injections may become relics of the past. The inhaler sprays insulin out into the mouth like a mist, which coats the membranes of the mouth, throat and tongue. The insulin then passes quickly through the membranes into the bloodstream. The new insulin inhaler is in phase two clinical trials. If all goes well, the Food and Drug Administration could put it on a fast track for approval, making it available on the market in less than two years. 

Maltesen M.J. Bjerregaard S. Hovgaard L. Havelund S. van de Weert M. Quality by design - Spray drying of insulin intended for inhalation. 

Ipratropium Atrovent HFA, Atrovent Nasal) [Bronchodilotor/ Anticholinergic] Uses Bronchospasm w/ COPD, rhinitis, rhinorrhea Action Synthetic anticholinergic similar to atropine antagonizes acetylcholine receptors, inhibits mucous gland secretions Dose Adults Feds >12 y. Nebuliza-tion 500 meg in 2.5-3.0 mL NS Feds. Nebulization 125-250 meg in 2.5-3.0 mL NS Caution [B, +/-] w/ inhal insulin Contra Allergy to soya lecithin/related foods Disp HFAmet-dose inhal 18 meg/dose inhal soln 0.02% nasal spray 0.03,... 

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. 

Alternative routes for administering insulin are also being considered.51 In particular, a form of insulin (Exubera) has been developed that can be administered by inhalation or nasal spray, thus precluding the need for subcutaneous injection.88,104 Other modifications of the insulin molecule or use of chemical enhancers can increase the permeability of this hormone so that insulin can be administered through the skin (transcu-taneously) or even via oral or buccal routes.2,35 Technologic and practical advancements in insulin delivery continue to be explored, and methods for administering insulin may be safer and more convenient in the future. 

A recent application of particle formation by solvent evaporation and spray-drying techniques is based on the concept of the aerodynamic diameter. According to Eq. (8.5), the aerodynamic diameter dAer is correlated with the true particle diameter dP and the particle density pp° 5. It is evident that particles formed in a particle-formation process can be much bigger, provided that their density is very small. Increased bioavailability of such large porous insulin particles (Fig. 8.14) has been demonstrated on inhalation by rats and has been correlated with a... 

Key Words Dry powder inhalers (DPI) Pulmonary drug delivery Insulin Particle engineering Spray drying Liposomes Aerosol solvent extraction system (ASES) Technosphere insulin. 

Stahl, K., et al. (2002) The effect of process variables on the degradation and physical properties of spray dried insulin intended for inhalation. International Journal of Pharmaceutics, 233 p. 227-237. 

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. ... 

Bi R, Shao W, Wang Q, Zhang N. Spray-freeze-dried dry powder inhalation of insulin-loaded liposomes for enhanced pulmonary delivery. /Drug Target. 2008 16(9) 639-48. 

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