Physicochemical compatibility of nebulizable drug mixtures containing dornase alfa and ipratropium and/or albuterol.
Patients suffering from cystic fibrosis (CF) often need to inhale multiple doses of different nebulizable drugs per day. Patients attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. The objective of this experimental study was to determine whether mixtures of Pulmozyme inhalation solution with Atrovent or Sultano are physicochemically compatible. Drug combinations were prepared in accordance with the product information and clinical practice by mixing the content of one respule Pulmozyme with 2 mL Atrovent LS and 0.5 mL Sultanol Inhalationslösung (inhalation solution) or with one respule of either Atrovent 500 microg/2 mL Fertiginhalat (unit dose formulation) or Sultanol forte Fertiginhalat. Test solutions were stored at room temperature and exposed to light. Dornase alfa activity was determined by a kinetic colorimetric DNase activity assay. Ipratropium bromide and albuterol concentrations were investigated by a stability-indicating HPLC assay with ultraviolet detection. Physical compatibility was determined by visual inspection and measurements of pH and osmolality. Ipratropium bromide and albuterol concentrations were not affected by mixing the drug products. Dornase alfa activity is affected by benzalkonium chloride, used as excipient in Atrovent"LS and Sultanol'Inhalationsl6öung, and disodium edetate used as an excipient in AtroventfLS. Patients should be advised not to mix Pulmozymelwith Atrovent1LS and/or Sultanol"Inhalationsldöung, because of the incompatibility reaction. Mixtures of Pulmozyme with Atrovent 500 microg/2 mL Fertiginhalat or Sultanol forte Fertiginhalat can be designated as compatible for a limited period of time.
Krämer
I
I
Department of Pharmacy, Johannes Gutenberg-Universität Mainz, Germany. Kraemer@apotheke.klinik.uni-mainz.de
Schwabe
A
A
Lichtinghagen
R
R
Kamin
W
W
D000280:Administration, Inhalation; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000737:chemistry*; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003850:Deoxyribonuclease I / Q000008:administration & dosage / Q000737:chemistry*; D004338:Drug Combinations; D004344:Drug Incompatibility; D006863:Hydrogen-Ion Concentration; D009241:Ipratropium / Q000008:administration & dosage / Q000737:chemistry*; D009330:Nebulizers and Vaporizers; D009994:Osmolar Concentration; D019999:Pharmaceutical Solutions
D018927:Anti-Asthmatic Agents; D004338:Drug Combinations; D019999:Pharmaceutical Solutions; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I; D009241:Ipratropium; D000420:Albuterol