title: Preparation of functional composite particles of salbutamol sulfate using a 4-fluid nozzle spray-drying technique.
abstract: A previous study on spray-drying demonstrated that it could promote the solubility of poorly water-soluble drugs using water-soluble polymers. Here, the preparation of composite particles of salbutamol sulfate (Sb) with water-insoluble polymers, such as Eudragit RS (RS) or Eudragit RL (RL) as a carrier, was examined. Despite the water insolubility of both polymers, the permeability of water was low in the former but high in the latter. We attempted to prepare controlled release composite particles by exploiting the characteristics of these carriers. The composite particles of the three components (Sb, RS, and RL) were prepared using a 4-fluid nozzle spray-dryer, and their physico-chemical and dissolution properties were compared with physical mixtures. Examination of particle morphology by scanning electron microscopy (SEM) revealed that the particles from the spray-drying process had atomized to several microns and were spherical. Analysis by X-ray diffraction and differential scanning calorimetry revealed that diffraction peaks and heat of fusion of Sb in the spray-dried samples decreased, indicating that the drug was amorphous and formed a solid dispersion. FT-IR analysis suggested that the amino group of Sb and a carbonyl group of the polymers formed a hydrogen bond. A dissolution test of Sb-RS-RL particles prepared using the 4-fluid nozzle spray-drying method showed that release rates were depressed significantly compared to the physical mixture at pH 1.2 and 6.8, and the depression was greater when RS was used instead of RL, presumably because of the permeability difference. The compression of these particles into tablets revealed that desirable controlled released dosage forms could be prepared. In addition, Sb was used to simulate an anti-asthmatic drug. For this an Andersen cascade impactor for dry powder inhalers was used to investigate delivery to the lungs.
authors.affiliation: Mintai Chemical Co., Ltd., 1142, Shin Hsing Rd, Bah-Der City, Taoyuan Hsien, Taiwan, ROC. chen@mingtai.com
authors.forename: Richer
authors.initials: R
authors.lastname: Chen
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okamoto
authors.forename: Kazumi
authors.initials: K
authors.lastname: Danjo
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000737:chemistry*; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry*; D000465:Algorithms; D002152:Calorimetry, Differential Scanning; D003890:Desiccation; D005079:Excipients; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011108:Polymers; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013607:Tablets; D014961:X-Ray Diffraction
chemical_list: D000318:Adrenergic beta-Agonists; D005079:Excipients; D011108:Polymers; D013607:Tablets; C058665:Eudragit RL; D000420:Albuterol