Inhalation spray-drying

Stevenson, C. Hastedt, J.E. Lehrman, S.R. Chiang, H.S. Bennett, D.B. Lesikar, D. Yang, B. Gong, D. Cabot, K. Inhaleable spray dried 4-helix bundle protein powders having minimized aggregation. US patent 6,569,406, Aug 7, 2001, Nektar Therapeutics San Carlos, CA. 

MT Vidgren, PA Vidgren, TP Paronen. Comparison of physical and inhalation properties of spray-dried and mechanically micronized disodium cromoglycate. Int J Pharm 35 139-144, 1987. 

M Sacchetti, MM Van Oort. Spray-drying and supercritical fluid particle generation techniques. Inhalation Aerosols Physical and Biological Basis for Therapy 1996 337-384. 

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

Inhalation drug products include inhalation aerosols (metered dose inhalers) inhalation solutions, suspensions, and sprays (administered via nebulizers) inhalation powders (dry powder inhalers) and nasal sprays. The CMC and preclinical considerations for inhalation drug products are unique in that these drug products are intended for respiratory tract-compromised patients. This is reflected in the level of concern given to the nature of the packaging components that may come in contact with the dosage form or the patient. 

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. 

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... 

Maa, Y., Nguyen, P., Sweeney, T., et al. Protein inhalation powders Spray drying vs. spray freeze drying. Pharm. Res. 16(2) 249-254, 1999. 

Maa et al. [3.84] used spray drying and spray freeze-drying (see Chapter 5, [5.13, 5.14]) to produce protein powders for inhalation from deoxyribonuclease (rhDNase) and anti-IgE monoclonal antibody (anti-IgE Mab) with lactose as carrier. Spray freezedrying produced light and porous protein particles with superior aerosol performance. 

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

Fig. 3. SEM images of various dry powders for inhalation, (a) Spray-dried particles (see Subheading 3.1.)- Reproduced from ref. 5. (b) Particles prepared by emulsification techniques (see Subheading 3.2.1.), Reproduced from ref. 10. (c) Particles prepared by supercritical C02 swelling (see Subheading 3.2.2.), The particles in panel b were the starting material for these particles. Reproduced from ref. 10. (d) TI particles (see Subheading 3.4.2.),...

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. 

Many of these techniques involve particle formation from solution formulations that contain novel excipients. Spray drying is the most advanced of these technologies and has been used to produce the powder formulation in the Exubera inhaler [175], Various modifications of this basic technique, including co-spray drying with novel excipients, have been employed. 

SAFETY PROFILE Moderately toxic by ingestion, inhalation, and skin contact. A severe skin and eye irritant. A very dangerous fire hazard when exposed to heat or flame can react vigorously with oxidizing materials. To fight fire, use alcohol foam, mist, spray, dry chemical. See also AMINES. 

To date, the two most successful ways for making powders for inhalation are spray drying and solvent precipitation. 

Spray drying involves converting the atomized liquid droplets into dry powders by hot air. This one-step process is capable of making particles of size suitable for inhalation.The particle size and size distribution of the powder can be manipulated by the concentration of the feed solution, the spray temperature, cyclone efficiency, and chemical nature of the feed. ... 

Pulmosphere. Pulmosphere (Inhale Therapeutic Systems, San Carlos, California, U.S.A.) particles are also prepared by spray drying, in which the feed comprises an aqueous solution containing dissolved or dispersed active drug, and a fluorocarbon-in-water emulsion, stabilized by a monolayer of phospholipid (such as dipalmitoylphosphatidylcholine). Being hollow and porous, Pulmosphere particles have a... 

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