Hydrophilic versus hydrophobic porogens for engineering of poly(lactide-co-glycolide) microparticles containing risedronate sodium.

OBJECTIVE: The aim of this study was to investigate the effect of two mechanistically different porogens, namely: the hydrophilic hydroxy-propyl-ß-cyclodextrin and the hydrophobic porogens (mineral oil and corn oil) in producing open/closed pored engineered polylactide-co-glycolic-acid microspheres suitable for pulmonary delivery of risedronate sodium (RS). MATERIALS AND METHODS: Surface morphology of the microspheres was studied and they were characterized for entrapment efficiency (%EE), particle size, and porosity as well as aerodynamic and flow properties. Selected formulae were investigated for in vitro drug release and deposition behavior using next generation impactor. Furthermore, the safety of the free drug and the selected prepared systems was assessed by MTT viability test performed on Calu-3 cell line. RESULTS AND DISCUSSION: The current work revealed that HP-ß-CD produced open-pored microspheres, while oils produced closed pored microspheres. Modulation of preparation parameters generated porous RS microspheres with high %EE, sustained drug release profile up to 15 days, suitable geometric and aerodynamic particle sizes and excellent flow properties. The safety of HP-ß-CD systems was higher than the systems utilizing oil as porogen. CONCLUSION: Porogen type affected the behavior of the microspheres as demonstrated by the various characterization experiments, with microspheres prepared using HP-ß-CD being superior to those prepared using oils as porogens.

A reliable predictive factorial model for entrapment optimization of a sodium bisphosphonate into biodegradable 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 µm. 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.

Different modalities of NaCl osmogen in biodegradable microspheres for bone deposition of risedronate sodium by alveolar targeting.

Risedronate sodium was formulated into polylactide-co-glycolic acid microspheres for pulmonary delivery using the w/o/w double emulsion technique. Sodium chloride was used as osmogen in either the internal or external aqueous phase to surface-engineer the particles to achieve favorable properties. The prepared microspheres were characterized for the surface morphology, entrapment efficiency, in vitro release behavior, particle size, surface area, aerodynamic as well as powder flow properties. Furthermore, the safety of the drug and the selected formula were assessed by MTT viability test performed on Calu-3 cell line as well as histopathological lung tissue examination. A novel in vivo approach based on the radiolabeling of risedronate sodium with I(125) was developed in order to assess its deposition in the bones of male albino rats. The majority of the prepared microspheres exhibited high entrapment efficiency, sustained release profile up to 15 days, suitable geometric and aerodynamic particle sizes as well as good flow properties. The safety of the drug and the selected formula were proven by the high cell viability percentage of Calu-3 cells as well as the normal lung histology after intra-tracheal administration. The in vivo study showed high bone deposition for risedronate sodium following the pulmonary route, suggesting that it could be utilized as an alternative route of administration for delivery of bisphosphonates.