title: Taste-masked tacrolimus-phospholipid nanodispersions: dissolution enhancement, taste masking and reduced gastric complications.
abstract: Through the integration of orthogonal central composite design and desirability function, this work aimed to explore the potential of quality by design in understanding the formulation of phospholipid-stabilized tacrolimus nanodispersions by microfluidization. The influence of homogenization pressure, microfluidization time and phospholipid concentration (X1-X3) on nanodispersion performance was studied. Nanodispersions were characterized by differential scanning calorimetric (DSC), X-ray diffractometer (XRD) and Fourier transform infrared (FTIR) analysis. Moreover, masking the unpalatable taste of tacrolimus and reducing the gastric complications were also evaluated. FTIR analysis indicated its interaction with phospholipid. DSC and XRD analysis revealed the amorphous transformation of tacrolimus within nanodispersions. The dissolution was enhanced by 35 folds and 15 folds after 0.5 and 2 h, respectively. Maximum tacrolimus content, yield, polydispersity index, percentages dissolved after 0.5 and 2 h of 99.3%, 100%, 0.864, 39.7% and 95.3%, respectively, with particle size of 160 nm were obtained at X1, X2 and X3 values of 20 000 psi, 6 min and 30%, respectively. The Euclidean distance values demonstrated masking the unpalatable taste and taste perversion to stimuli of tacrolimus in its optimized nanodispersion. Moreover, the ulcerative indices following raw tacrolimus and its optimized nanodispersion oral administration were 6.73 and 2.45, respectively, to indicate that nanodispersion was significantly less irritating to the gastric mucosa.
authors.affiliation: a Department of Pharmaceutics and Industrial Pharmacy , Faculty of Pharmacy, King Abdulaziz University , Jeddah , Saudi Arabia and.|b Department of Pharmaceutics and Industrial Pharmacy , Faculty of Pharmacy, Zagazig University , Zagazig , Egypt.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Zidan
mesh_terms: D000818:Animals; D004339:Drug Compounding / Q000379:methods*; D062609:Electronic Nose; D005079:Excipients / Q000737:chemistry*; D041981:Gastrointestinal Tract / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012995:Solubility; D016559:Tacrolimus / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D013649:Taste / Q000187:drug effects; D055697:Taste Perception / Q000187:drug effects*
chemical_list: D005079:Excipients; D007166:Immunosuppressive Agents; D010743:Phospholipids; D016559:Tacrolimus
keywords: Gastroprotection; microfluidization; nanodispersion; tacrolimus; taste masking