title: Design and development of intraocular polymeric implant systems for long-term controlled-release of clindamycin phosphate for toxoplasmic retinochoroiditis.
abstract: BACKGROUND
  The release of the anti-toxoplasmosis drug, clindamycin phosphate, from intraocular implants of the biodegradable polymers poly (D, L-lactic acid) (PLA) and poly (D, L-lactide-co-glycolide) (PLGA) has been studied in vitro.
  
  
  METHODS
  The preparation of the implants was performed by a melt-extrusion method. The developed extrudates were characterized and compared in in-vitro release profiles for elucidating the drug release mechanism. The formulations containing up to 40% w/w of drug were prepared. Release data in phosphate buffer (pH 7.4) were analyzed by high performance liquid chromatography. The release kinetics were fitted to the zero-order, Higuchi's square-root, first order and the Korsmeyer-Peppas empirical equations for the estimation of various parameters of the drug release curves. Degradation of implants was also investigated morphologically with time (Scanning Electron Microscopy).
  
  
  RESULTS
  It was observed that, the release profiles for the formulations exhibit a typical biphasic profile for bulk-eroding systems, characterized by a first phase of burst release (in first 24 hrs), followed by a phase of slower release. The duration of the secondary phase was found to be proportional to the molecular weight and monomer ratio of copolymers and also polymer-to-drug ratios. It was confirmed that Higuchi and first-order kinetics were the predominant release mechanisms than zero order kinetic. The Korsmeyer-Peppas exponent (n) ranged between 0.10 and 0.96. This value, confirmed fickian as the dominant mechanism for PLA formulations (n ≤ 0.45) and the anomalous mechanism, for PLGAs (0.45 < n < 0.90).
  
  
  CONCLUSIONS
  The implant of PLA (I.V. 0.2) containing 20% w/w of clindamycin, was identified as the optimum formulation in providing continuous efficient in-vitro release of clindamycin for about 5 weeks.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Lana
authors.initials: L
authors.lastname: Tamaddon
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: S Abolfazl
authors.initials: SA
authors.lastname: Mostafavi
authors.affiliation: Department of Ophthalmology, Eye Research Center, Farabi Eye Hospital, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Karkhane
authors.affiliation: Department of Ophthalmology, Eye Research Center, Farabi Eye Hospital, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Riazi-Esfahani
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farid Abedin
authors.initials: FA
authors.lastname: Dorkoosh
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Rafiee-Tehrani
keywords: Clindamycin phosphate; PLA; PLGA; intraocular implant