Freeze Thaw: A Simple Approach for Prediction of Optimal Cryoprotectant for Freeze Drying |
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Authors: | Praveen V Date Abdul Samad Padma V Devarajan |
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Institution: | (1) Department of Pharmaceutical Sciences and Technology (Deemed University), Institute of Chemical Technology, N.P. Marg, Matunga (E), Mumbai, 400019, Maharastra, India;(2) Bombay Veterinary College, Parel, Mumbai, 400012, India; |
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Abstract: | The present study evaluates freeze thaw as a simple approach for screening the most appropriate cryoprotectant. Freeze–thaw
study is based on the principle that an excipient, which protects nanoparticles during the first step of freezing, is likely
to be an effective cryoprotectant. Nanoparticles of rifampicin with high entrapment efficiency were prepared by the emulsion-solvent
diffusion method using dioctyl sodium sulfosuccinate (AOT) as complexing agent and Gantrez AN-119 as polymer. Freeze–thaw
study was carried out using trehalose and fructose as cryoprotectants. The concentration of cryoprotectant, concentration
of nanoparticles in the dispersion, and the freezing temperature were varied during the freeze–thaw study. Cryoprotection
increased with increase in cryoprotectant concentration. Further, trehalose was superior to fructose at equivalent concentrations
and moreover permitted use of more concentrated nanosuspensions for freeze drying. Freezing temperature did not influence
the freeze–thaw study. Freeze-dried nanoparticles revealed good redispersibility with a size increase that correlated well
with the freeze–thaw study at 20% w/v trehalose and fructose. Transmission electron microscopy revealed round particles with a size ∼400 nm, which correlated with
photon correlation spectroscopic measurements. Differential scanning calorimetry and X-ray diffraction suggested amorphization
of rifampicin. Fourier transfer infrared spectroscopy could not confirm interaction of drug with AOT. Nanoparticles exhibited
sustained release of rifampicin, which followed diffusion kinetics. Nanoparticles of rifampicin were found to be stable for
12 months. The good correlation between freeze thaw and freeze drying suggests freeze–thaw study as a simple and quick approach
for screening optimal cryoprotectant for freeze drying. |
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