TY - JOUR
T1 - Optimization and validation of stability indicating RP-HPLC method for the quantification of gefitinib in bulk drug and nanoformulations
T2 - An application towards in vitro and ex vivo performance evaluation
AU - Kumar, Pankaj
AU - Mangla, Bharti
AU - Beg, Sarwar
AU - Afzal, Obaid
AU - Saleh Altamimi, Abdulmalik
AU - Almalki, Waleed H.
AU - Nasar Mir Najib Ullah, Shehla
AU - Aggarwal, Geeta
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/12
Y1 - 2022/12
N2 - Gefitinib (GFB) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used primarily to treat non-small cell lung cancer (NSCLC), but it also works by lowering AKT and MAPK phosphorylation, which makes it effective against the breast cancer cells. A high-performance liquid chromatography (HPLC) method was developed for detecting gefitinib by C18 analytical column with mobile phase containing acetonitrile and 1 % w/v ammonium acetate in water with ratio of 60:40. Box-Behnken design was used to optimize the chromatographic conditions, and method was validated for accuracy, precision, linearity, robustness, ruggedness, limit of detection, and limit of quantification. The developed method was found to be useful in estimating gefitinib in conventional marketed tablet dosage forms and nanoformulations such as SLNs and liposomes. With a calibration curve, linearity was attained in the drug concentration range of 8–56 µg/mL (r2 = 0.9996), and sensitivity was found to be 1.3 and 3.9 µg/mLas LOD and LOQ, respectively. All the validation criteria for the method were within the acceptable limits. The drug content in the conventional tablet formulation was found to be 99.99 %. The HPLC analysis indicated that gefitinib was highly soluble in Precirol ATO5 as solid lipid and tween 80 as surfactant. Drug entrapment efficiency was found to be 83.1 % and 80.5 % for SLNs and liposomes respectively. In vitro release data revealed that 30 % of drug was released from plain suspension and more than 77 % released from both nanoformulations after 24 h at pH 7.4 respectively. By applying kinetic fit, data was most appropriately fitted into first order as compared to other. The apparent permeability of gefitinib from plain suspension, SLNs and Liposomes was found to be 3.98 × 10−4 cm/min, 1.35 × 10−4 cm/min and 1.79 × 10−4 cm/min.
AB - Gefitinib (GFB) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used primarily to treat non-small cell lung cancer (NSCLC), but it also works by lowering AKT and MAPK phosphorylation, which makes it effective against the breast cancer cells. A high-performance liquid chromatography (HPLC) method was developed for detecting gefitinib by C18 analytical column with mobile phase containing acetonitrile and 1 % w/v ammonium acetate in water with ratio of 60:40. Box-Behnken design was used to optimize the chromatographic conditions, and method was validated for accuracy, precision, linearity, robustness, ruggedness, limit of detection, and limit of quantification. The developed method was found to be useful in estimating gefitinib in conventional marketed tablet dosage forms and nanoformulations such as SLNs and liposomes. With a calibration curve, linearity was attained in the drug concentration range of 8–56 µg/mL (r2 = 0.9996), and sensitivity was found to be 1.3 and 3.9 µg/mLas LOD and LOQ, respectively. All the validation criteria for the method were within the acceptable limits. The drug content in the conventional tablet formulation was found to be 99.99 %. The HPLC analysis indicated that gefitinib was highly soluble in Precirol ATO5 as solid lipid and tween 80 as surfactant. Drug entrapment efficiency was found to be 83.1 % and 80.5 % for SLNs and liposomes respectively. In vitro release data revealed that 30 % of drug was released from plain suspension and more than 77 % released from both nanoformulations after 24 h at pH 7.4 respectively. By applying kinetic fit, data was most appropriately fitted into first order as compared to other. The apparent permeability of gefitinib from plain suspension, SLNs and Liposomes was found to be 3.98 × 10−4 cm/min, 1.35 × 10−4 cm/min and 1.79 × 10−4 cm/min.
KW - Breast cancer
KW - Experimental design
KW - Gefitinib
KW - Marketed tablet
KW - Method validation
KW - Permeationstudy
UR - http://www.scopus.com/inward/record.url?scp=85140782267&partnerID=8YFLogxK
U2 - 10.1016/j.arabjc.2022.104333
DO - 10.1016/j.arabjc.2022.104333
M3 - Article
AN - SCOPUS:85140782267
SN - 1878-5352
VL - 15
JO - Arabian Journal of Chemistry
JF - Arabian Journal of Chemistry
IS - 12
M1 - 104333
ER -
