Formation of phenytoin nanoparticles using rapid expansion of supercritical solution with solid cosolvent (RESS-SC) process

• Published in: International journal of pharmaceutics 2006-02, Vol.308 (1), p.190-199
• Main Authors: Thakur, Ranjit, Gupta, Ram B.
• Format: Article
• Language: English
• Subjects: Anticonvulsants - chemistry; Biological and medical sciences; Carbon Dioxide - chemistry; Crystallization; General pharmacology; Medical sciences; Menthol - chemistry; Microscopy, Electron, Scanning; Nanoparticle; Nanostructures; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phenytoin; Phenytoin - chemistry; Pressure; RESS; RESS-SC; Solubility; Solvents - chemistry; Spectroscopy, Fourier Transform Infrared; Supercritical; Surface Properties; Technology, Pharmaceutical - instrumentation; Technology, Pharmaceutical - methods; Temperature; X-Ray Diffraction
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2005.11.005

Nanoparticles are of significant importance in drug delivery. Rapid expansion of supercritical solution (RESS) process can produce pure and high-quality drug particles. However, due to extremely low solubility of polar drugs in supercritical CO 2 (sc CO 2), RESS has limited commercial applicability. To overcome this major limitation, a modified process rapid expansion of supercritical solution with solid cosolvent (RESS-SC) is proposed which uses a solid cosolvent. Here, the new process is tested for phenytoin drug using menthol solid cosolvent. Phenytoin solubility in pure sc CO 2 is only 3 μmol/mol but when menthol solid cosolvent is used the solubility is enhanced to 1302 μmol/mol, at 196 bar and 45 °C. This 400-fold increase in the solubility can be attributed to the interaction between phenytoin and menthol. Particle agglomeration in expansion zone is another major issue with conventional RESS process. In proposed RESS-SC process solid cosolvent hinders the particle growth resulting in the formation of small nanoparticles. For example, the average particle size of phenytoin in conventional RESS process is 200 nm whereas, with RESS-SC process, the average particle size is 120 nm, at 96 bar and 45 °C. Similarly at 196 bar and 45 °C, 105 nm average particles were obatined by RESS and 75 nm average particles were obtained in RESS-SC process. The particles obtained were characterized by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS) and differential scanning calorimetery (DSC) analyses. Phenytoin nanoparticle production rate in RESS-SC is about 400-fold more in comparision to that in RESS process.