title: Nebulization of mycophenolate mofetil inhalation suspension in rats: comparison with oral and pulmonary administration of Cellcept®.
abstract: In this study, a suspension of mycophenolate mofetil (MMF) suitable for inhalation was developed using the emulsion template process and characterized for particle size and aerosolization performance. To evaluate the benefits of this suspension over a solution, the IV Cellcept(®) solution was also characterized in vitro. Both formulations exhibited excellent aerosolization performance. The aerodynamic diameters for the solution and the suspension were within the respirable range (below 5μm) and their fine particle doses were nearly equivalent, suggesting the same drug exposure during in vivo experiments. Single dose 24-h pharmacokinetic studies following inhalation of the formulations and oral administration of oral Cellcept(®) were performed in rats. Following oral administration, MMF was completely and rapidly metabolized into its active metabolite, mycophenolic acid (MPA) and partial metabolism was observed following pulmonary administration. Inhaled MMF suspension displayed more favorable pharmacokinetics than inhaled IV Cellcept(®) solution, but the MPA drug levels in each compartment were much lower than those obtained with oral Cellcept(®). The dose normalized MPA levels in the lung, thymus gland and plasma following inhalation of the MMF suspension with the oral control suggested that pulmonary delivery of a MMF suspension could be beneficial in preventing lung allograft rejection.
authors.affiliation: College of Pharmacy, Pharmaceutics Division, The University of Texas at Austin, TX, USA. hdugas@utexas.edu
authors.forename: Hélène L
authors.initials: HL
authors.lastname: Dugas
authors.forename: Jay I
authors.initials: JI
authors.lastname: Peters
authors.forename: Robert O
authors.initials: RO
authors.lastname: Williams
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D004655:Emulsions; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid