Effects of carriers and storage of formulation on the lung deposition of a hydrophobic and hydrophilic drug from a DPI

• Published in: International journal of pharmaceutics 2003-09, Vol.263 (1), p.151-163
• Main Authors: Harjunen, Päivi, Lankinen, Tapio, Salonen, Heikki, Lehto, Vesa-Pekka, Järvinen, Kristiina
• Format: Article
• Language: English
• Subjects: Albuterol - pharmacokinetics; Biological and medical sciences; Budesonide; Budesonide - pharmacokinetics; Chemistry, Pharmaceutical; Drug Carriers - analysis; Drug Carriers - pharmacokinetics; Drug Carriers - pharmacology; Drug Storage; General pharmacology; Glucose; Glucose - pharmacokinetics; Glucose - pharmacology; Hydrophobic and Hydrophilic Interactions; In Vitro Techniques; Inhalation powder; Lactose; Lung - metabolism; Mannitol; Mannitol - pharmacokinetics; Mannitol - pharmacology; Medical sciences; Nebulizers and Vaporizers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Powders - analysis; Powders - pharmacokinetics; Powders - pharmacology; Respiratory system; Salbutamol sulphate
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(03)00357-0

The effects of carriers, the drug:carrier ratio and a 1 month storage period of a formulation in permeable polystyrene tube at 40 °C/75% RH on the in vitro pulmonary deposition of model drugs from dry powder inhaler (DPI) were evaluated. Budesonide (hydrophobic) and salbutamol sulphate (hydrophilic) were used as model drugs. Mannitol and glucose were used as the carriers. In addition, lactose 110 M was used as the carrier for budesonide. The novel multiple dose Taifun ® was used as a DPI; Taifun ® is a breath-actuated inhaler that contains the powder formulation in a reservoir chamber. The respirable fractions (RF%) values of the drugs were determined by the “Andersen” sampler. The RF% values of salbutamol sulphate increased with an increase in the drug:carrier ratio before storage, whereas the drug:carrier ratio did not affect the RF% values after storage. In the case of budesonide, the drug:carrier ratio did not affect the RF% values before storage, instead the RF% values of budesonide increased with an increase in the drug:carrier ratio after storage. The RF% values of salbutamol sulphate decreased after storage of the formulation, this was not dependent on the carrier and the drug:carrier ratio. However, with budesonide the effect of the storage on its RF% values was dependent on which carrier was used and also the drug:carrier ratio. Overall, storage had less effect on the RF% values of budesonide than those of salbutamol sulphate. The highest RF% values of budesonide were obtained when mannitol was used as the carrier. Furthermore, the RF% values of salbutamol sulphate tended to be higher when mannitol was used as the carrier instead of glucose.