Titre du document / Document title

Investigation into the effect of humidity on drug-drug interactions using the atomic force microscope

Auteur(s) / Author(s)

YOUNG Paul M. ⁽¹⁾ ; PRICE Robert ⁽¹⁾ ; TOBYN Michael J. ⁽¹⁾ ; BUTTRUM Mark ⁽²⁾ ; DEY Fiona ⁽²⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Pharmaceutical Technology Research Group, Department of Pharmacy and Pharmacology, University of Bath, BA2 7AY, ROYAUME-UNI
⁽²⁾ Respiratory Technology, Aventis Pharma, Holmes Chapel, CW4 8BE, ROYAUME-UNI

Résumé / Abstract

The atomic force microscope (AFM) has been used to characterize the cohesive nature of a micronized pharmaceutical powder used for inhalation therapy. Salbutamol sulfate (also referred to as albuterol sulfate), a therapeutic drug commonly delivered from dry powder inhalers (DPI), was chosen as a model system because the cohesion and subsequent de-agglomeration during inhalation are critical aspects to the efficacy of such a delivery system. Salbutamol sulfate drug particulates were mounted on V-shaped AFM cantilevers using a novel micromanipulation technique. Force-distance curves obtained from the measurements between cantilever drug probes and model compacts of salbutamol sulfate were integrated to determine separation energies. The effect of humidity (15-75% RH) on the energy required to separate a drug particle from model drug surface was determined using a custom-built perfusion apparatus attached to the AFM. Separation energy measurements over 10 x 10-μm areas of the compact surface (n = 4096) exhibited log normal distributions (apparent linear regression, R²≥0.97). Significant increases in the median separation energies (p<0.05) between the salbutamol sulfate drug probes and salbutamol sulfate model surfaces were observed as humidity was increased. This result is most likely attributed to capillary interactions becoming more dominant at higher humidities. This investigation has shown the AFM to be a powerful technique for quantification of the separation energies between micronized drug particulates, highlighting the potential of the AFM as a rapid preformulation tool.

Revue / Journal Title

Journal of pharmaceutical sciences   ISSN 0022-3549   CODEN JPMSAE 

Source / Source

2003, vol. 92, n^o4, pp. 815-822 [8 page(s) (article)] (23 ref.)

Langue / Language

Anglais

Editeur / Publisher

American Pharmaceutical Association, Washington, DC, ETATS-UNIS  (1961) (Revue)

Mots-clés anglais / English Keywords

Salbutamol ; Micronization ; Atomic force microscopy ; Powder ; Inhaler ; Humidity ; Drug interaction ;

Mots-clés français / French Keywords

Salbutamol ; Micronisation ; Microscopie force atomique ; Poudre ; Inhalateur ; Humidité ; Interaction médicamenteuse ;

Mots-clés espagnols / Spanish Keywords

Salbutamol ; Micronización ; Microscopía fuerza atómica ; Polvo ; Inhalador ; Humedad ; Interacción medicamentosa ;

Mots-clés d'auteur / Author Keywords

dry powder aerosolization ; humidity ; atomic force microscope ; force volume ;

Localisation / Location

INIST-CNRS, Cote INIST : 3209 A, 35400011792844.0100