A Reliable Predictive Factorial Model for Entrapment Optimization of a Sodium Bisphosphonate into Biodegradable Microspheres

作者：Nasr Maha; Awad Gehanne A S; Mansour Samar; Al Shamy Abdelhamid; Mortada Nahed D^*

来源：Journal of Pharmaceutical Sciences, 2011, 100(2): 612-621.

DOI：10.1002/jps.22297

• biodegradable polymers
• encapsulation
• factorial design
• formulation
• mathematical model
• microencapsulation
• polymeric drug delivery systems
• microspheres

The aim of this work was to optimize the encapsulation of a third generation bisphosphonate (risedronate sodium RS) into polylactide-co-glycolide (PLGA) microspheres using a double emulsion technique for implant purposes. Microspheres were prepared by w/o/w double emulsion technique using PLGA in the ratio of 50:50 and 75:25. Critical process parameters namely: polymer type and amount, drug amount and internal aqueous phase volume ratio were evaluated for their effect on entrapment efficiency (EE%) of RS. Microspheres were characterized for their entrapment efficiency, morphology and particle size by UV spectrophotometry, scanning electron microscopy, and laser diffraction respectively. A 2(4) full factorial design was used for model production. High EE% exceeding 80% were obtained through the manipulation of the previously mentioned factors. Microparticles showed smooth surface with few pores and a size ranging from 1-6 mu m. The factorial mathematical model was validated by check point analysis revealing good agreement between actual and predicted values. PLGA microspheres successfully encapsulated RS at high levels with suitable size and morphology suggesting their potential use in the treatment of bone diseases as injectable implants.

• 出版日期2011-2