Parenteral formulation of an anticancer drug candidate – Tackling poor solubility
1 Introduction
Cancer is the number one cause of death in Singapore , and has been on an increasing trend over the years . Hence, the search for anti-cancer drugs and better treatment regimens are widely studied but there are many challenges. One potential cancer treatment strategy is to induce apoptosis in cancer tissues by the modulation of nitric oxide production .
Nitric oxide is a reactive, gaseous molecule formed from the catalytic oxidation of L-arginine to L-citrulline by the nitric oxide synthase (NOS). It has been shown to be associated with the development and progression of cancer by mediating tumour angiogenesis and metastasis3. Hence, inhibiting …show more content…
With low drug solubility but high intravenous dose required, there is a problem in the preparation of L-NNA as a parenteral product.
The incorporation of highly soluble adjuvants can improve the solubility of L-NNA. The types of adjuvants and conditions for improving the solubility of L-NNA will be studied by first screening adjuvants for their potential to improve the solubility of …show more content…
All measurements were carried out at room temperature with a 1.0 cm × 1.0 cm quartz glass cuvette. Prior to measurements, each sample was diluted accordingly such that absorbance fall within linear range of the calibration curve (R2 = 0.9999). All the data presented represent the mean of, at least, three determinations.
3.5 High Performance Liquid Chromatography
Monitoring of stability of L-NNA was performed using HPLC on a Shimadzu (Kyoto, Japan) system that was equipped with a SIL-10AD auto injector, DGU-20A5 degasser, LC-20AT …, SPD-M10A diode array detector and CTO-10AC column oven. A 5µm, C8 4.6 mm x 250 mm column (…) was used, controlled at 40C. Gradient elution was used with 95% acetonitrile and 5% acidified MilliQ water (titrated to pH 2.5 using hydrochloric acid) from 0 – 10 min, 1% acetonitrile and 95% acidified MilliQ water from 11 – 20 min and 95% acetonitrile and 1% MilliQ water from 21 – 35 min. The flow rate was set at 0.5 mL/min and a wavelength of 269 nm was used. Sample solutions were injected at a volume of 1µL. The HPLC was calibrated with standard solutions of 0.5 – 2.5 mg/mL of L-NNA dissolved in MilliQ water (R2 = 0.9954). All the data presented represent the mean of, at least, three
1 Introduction
Cancer is the number one cause of death in Singapore , and has been on an increasing trend over the years . Hence, the search for anti-cancer drugs and better treatment regimens are widely studied but there are many challenges. One potential cancer treatment strategy is to induce apoptosis in cancer tissues by the modulation of nitric oxide production .
Nitric oxide is a reactive, gaseous molecule formed from the catalytic oxidation of L-arginine to L-citrulline by the nitric oxide synthase (NOS). It has been shown to be associated with the development and progression of cancer by mediating tumour angiogenesis and metastasis3. Hence, inhibiting …show more content…
With low drug solubility but high intravenous dose required, there is a problem in the preparation of L-NNA as a parenteral product.
The incorporation of highly soluble adjuvants can improve the solubility of L-NNA. The types of adjuvants and conditions for improving the solubility of L-NNA will be studied by first screening adjuvants for their potential to improve the solubility of …show more content…
All measurements were carried out at room temperature with a 1.0 cm × 1.0 cm quartz glass cuvette. Prior to measurements, each sample was diluted accordingly such that absorbance fall within linear range of the calibration curve (R2 = 0.9999). All the data presented represent the mean of, at least, three determinations.
3.5 High Performance Liquid Chromatography
Monitoring of stability of L-NNA was performed using HPLC on a Shimadzu (Kyoto, Japan) system that was equipped with a SIL-10AD auto injector, DGU-20A5 degasser, LC-20AT …, SPD-M10A diode array detector and CTO-10AC column oven. A 5µm, C8 4.6 mm x 250 mm column (…) was used, controlled at 40C. Gradient elution was used with 95% acetonitrile and 5% acidified MilliQ water (titrated to pH 2.5 using hydrochloric acid) from 0 – 10 min, 1% acetonitrile and 95% acidified MilliQ water from 11 – 20 min and 95% acetonitrile and 1% MilliQ water from 21 – 35 min. The flow rate was set at 0.5 mL/min and a wavelength of 269 nm was used. Sample solutions were injected at a volume of 1µL. The HPLC was calibrated with standard solutions of 0.5 – 2.5 mg/mL of L-NNA dissolved in MilliQ water (R2 = 0.9954). All the data presented represent the mean of, at least, three