title: Physicochemical characterization of sildenafil-loaded solid lipid nanoparticle dispersions (SLN) for pulmonary application.
abstract: For the development of any colloidal system, thorough characterization is extremely essential. This article discusses the physicochemical characterization of sildenafil-loaded solid lipid nanoparticle dispersions (SLN) including stability analysis over 6 months time period for possible pulmonary administration for the treatment of pulmonary arterial hypertension (PAH). SLN consisting of phospholipid and triglycerides were manufactured using a novel microchannel homogenization method. These sildenafil-loaded SLN were then subjected to physicochemical characterization namely, particle size and distribution over shelf life, differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and analysis of nebulization performance of these SLN by the means of next generation impactor (NGI). Additionally, the morphology of nebulized particles was assessed by transmission electron microscopy using negative staining technique. The solubility of sildenafil citrate and base in the lipid matrix was determined and was 0.1% w/w and 1% w/w, respectively. From the particle size measurements, it was observed that SLN without sildenafil demonstrated consistent particle sizes over 6 months. For the sildenafil-loaded SLN, increased particle sizes were found after manufacturing and further increased within weeks. From WAXD studies, after 6 months high intensity reflections corresponding to the stable β modification were observed. From DSC results, the peak minimum temperatures increased upon storage, hinting at a transformation to the stable β modification of triglycerides in the case of sildenafil-loaded SLN. Hence, it can be concluded that even small drug concentration influences particle size and stability.
authors.affiliation: Institut für Pharmazeutische Technologie, TU Braunschweig, Mendelssohnstr.1, 38106 Braunschweig, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Paranjpe
authors.affiliation: Institut für Pharmazeutische Technologie, TU Braunschweig, Mendelssohnstr.1, 38106 Braunschweig, Germany; Institut für Partikeltechnik, TU Braunschweig, Volkmaroder Str. 5, 38104 Braunschweig, Germany.
authors.forename: J H
authors.initials: JH
authors.lastname: Finke
authors.affiliation: Institut für Mikrotechnik, TU Braunschweig, Alte Salzdahlumer Str. 203, 38124 Braunschweig, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Richter
authors.affiliation: Institut für Partikeltechnik, TU Braunschweig, Volkmaroder Str. 5, 38104 Braunschweig, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Gothsch
authors.affiliation: Institut für Partikeltechnik, TU Braunschweig, Volkmaroder Str. 5, 38104 Braunschweig, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kwade
authors.affiliation: Institut für Mikrotechnik, TU Braunschweig, Alte Salzdahlumer Str. 203, 38124 Braunschweig, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Büttgenbach
authors.affiliation: Institut für Pharmazeutische Technologie, TU Braunschweig, Mendelssohnstr.1, 38106 Braunschweig, Germany. Electronic address: c.mueller-goymann@tu-braunschweig.de.
authors.forename: C C
authors.initials: CC
authors.lastname: Müller-Goymann
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D004356:Drug Storage; D008055:Lipids / Q000737:chemistry*; D008168:Lung / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D010316:Particle Size; D058986:Phosphodiesterase 5 Inhibitors / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D010879:Piperazines / Q000008:administration & dosage* / Q000737:chemistry; D011687:Purines / Q000008:administration & dosage / Q000737:chemistry; D000068677:Sildenafil Citrate; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry; D014280:Triglycerides / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D008055:Lipids; D058986:Phosphodiesterase 5 Inhibitors; D010743:Phospholipids; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D014280:Triglycerides; D000068677:Sildenafil Citrate
keywords: Microchannel homogenization; Next generation impactor (NGI); Physicochemical characterization; Pulmonary administration; Sildenafil; Solid lipid nanoparticles (SLN)