title: Development of meloxicam in situ implant formulation by quality by design principle.
abstract: OBJECTIVE
  The focus of this study was to develop and optimize in situ implant formulation of meloxicam by quality by design (QbD) principle for long-term management of musculoskeletal inflammatory disorders.
  
  
  METHODS
  The formulation was optimized by Box-Behnken design with polylactide-co-glycolide (PLGA) level (X1), N-methyl pyrrolidone level (X2) and PLGA intrinsic viscosity (X3) as the independent variables and initial burst release of drug (Y1), cumulative release (Y2), and dissolution efficiency (Y3) as the dependent variables. The formulation was physicochemically characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy and powder X-ray diffraction (PXRD). Pharmacokinetic studies of the optimized formulation were performed on Sprague-Dawley rats.
  
  
  RESULTS
  Y1 was significantly affected by X2 and X3. Y2 was affected by X1 and X3 while Y3 was affected by all three independent variables employed in the formulations. Responses for the optimized formulation were in close agreement with the values predicted by the model. SEM photomicrographs indicated uniform gel formulation. No chemical interaction between the components of formulation was observed by FT-IR and meloxicam was found to be present in the amorphous form in the gel matrix as revealed by PXRD. The maximum plasma concentration (Cmax), time to achieve Cmax and area under plasma concentration curve were significantly different from those of the solution formulation used as the control. Plasma concentration of meloxicam was maintained above its IC50 concentration required for COX-2 inhibition for 23 days.
  
  
  CONCLUSIONS
  Meloxicam in situ implant may provide long-term management of inflammatory conditions with improved patient compliance and better therapeutic index.
authors.affiliation: Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University Health Science Center , Kingsville, TX , USA.
authors.forename: Hany M
authors.initials: HM
authors.lastname: Ibrahim
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Ahmed
authors.forename: Muhammad D
authors.initials: MD
authors.lastname: Hussain
authors.forename: Ziyaur
authors.initials: Z
authors.lastname: Rahman
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Samy
authors.forename: Ala A
authors.initials: AA
authors.lastname: Kaseem
authors.forename: Mohammad T H
authors.initials: MT
authors.lastname: Nutan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D004343:Drug Implants; D005782:Gels; D020128:Inhibitory Concentration 50; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D000077239:Meloxicam; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011760:Pyrrolidinones / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared; D013843:Thiazines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D013844:Thiazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014783:Viscosity; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D004343:Drug Implants; D005782:Gels; D011760:Pyrrolidinones; D013843:Thiazines; D013844:Thiazoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C038678:N-methylpyrrolidone; D000077239:Meloxicam