Investigations on the Humidity-Induced Transformations of Salbutamol Sulphate Particles Coated with l-Leucine

• Published in: Pharmaceutical research Vol. 25; no. 10; pp. 2250 - 2261
• Main Authors: Raula, Janne, Thielmann, Frank, Kansikas, Jarno, Hietala, Sami, Annala, Minna, Seppälä, Jukka, Lähde, Anna, Kauppinen, Esko I.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2008; Springer; Springer Nature B.V
• Subjects: Albuterol - chemistry; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Bronchodilator Agents - chemistry; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Crystallization; Drug Stability; General pharmacology; Humidity; Leucine - chemistry; Medical Law; Medical sciences; Microscopy, Electron, Scanning; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Powders; Process engineering; Research methodology; Research Paper; Rheology; Technology, Pharmaceutical - methods; Temperature; Water - chemistry; crystallization; humidity; leucine coating; salbutamol sulphate; stability; Agonist; L-leucine coating; Stability; Pharmaceutical technology; Bronchodilator; Crystallization; β2-Adrenergic receptor; β-Adrenergic receptor agonist; Leucine; Aminoacid; Humidity; Coated particle; Salbutamol; Coating; Physicochemical properties
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-008-9613-4

Purpose The crystallization and structural integrity of micron-sized inhalable salbutamol sulphate particles coated with l -leucine by different methods are investigated at different humidities. The influence of the l -leucine coating on the crystallization of salbutamol sulphate beneath the coating layer is explored. Methods The coated particles are prepared by an aerosol flow reactor method, the formation of the l -leucine coating being controlled by the saturation conditions of the l -leucine. The coating is formed by solute diffusion within a droplet and/or by vapour deposition of l -leucine. The powders are humidified at 0%, 44%, 65% and 75% of relative humidity and the changes in physical properties of the powders are investigated with dynamic vapour sorption analysis (DVS), a differential scanning calorimeter (DSC), and a scanning electron microscope (SEM). Results Visual observation show that all the coated particles preserve their structural integrity whereas uncoated salbutamol sulphate particles are unstable at 65% of relative humidity. The coating layer formed by diffusion performs best in terms of its physical stability against moisture and moisture-induced crystallization. The degree of crystallization of salbutamol in the as-prepared powders is within the range 24–35%. The maximum degree of crystallization after drying ranges from 55 to 73% when the salbutamol crystallizes with the aid of moisture. In addition to providing protection against moisture, the l -leucine coating also stabilizes the particle structure against heat at temperatures up to 250°C. Conclusion In order to preserve good flowability together with good physical stability, the best coating would contain two l -leucine layers, the inner layer being formed by diffusion (physical stability) and the outer layer by vapour deposition (flowability).