58. Thakur, Ranjit; Gupta, Ram B.. Formation of phenytoin nanoparticles using rapid expansion of
supercritical solution with solid cosolvent (RESS-SC) process. International Journal of Pharmaceutics (2006), 308(1-2),
Nanoparticles are of significant importance in drug
expansion of supercrit. soln. (RESS) process can produce pure and
high-quality drug particles. However, due to extremely low soly. of
polar drugs in supercrit. CO2 (s.c. CO2), RESS has limited com.
applicability. To overcome this major
limitation, a modified process rapid expansion of supercrit. soln. 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 soly. in pure s.c.
CO2 is only 3 mmol/mol but when
menthol solid cosolvent is used the soly. is enhanced to 1302 mmol/mol, at 196 bar and 45 °C.
This 400-fold increase in the soly. 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 av. particle
size of phenytoin in conventional RESS process is 200 nm whereas, with RESS-SC
process, the av. particle size is 120 nm, at 96 bar and 45 °C.
Similarly at 196 bar and 45 °C,
105 nm av. particles were obtained by RESS and 75 nm av. particles were
obtained in RESS-SC process. The
particles obtained were characterized by Fourier-transform IR spectroscopy
(FTIR), x-ray diffraction (XRD), dynamic light scattering (DLS) and
differential scanning calorimetry (DSC) analyses. Phenytoin nanoparticle prodn. rate in RESS-SC
is about 400-fold more in comparison to that in RESS process.
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