Application of HPLC to assess the compatibility of bisoprolol fumarate with selected excipients in mixtures by isothermal stress testing.

In the present study, the compatibility between bisoprolol fumarate and selected excipients (ascorbic acid, citric acid anhydrous, butylated hydroxyanisole, polyvinylpyrrolidone, glycerol, mannitol and sorbitol) in mixtures (1:10 ratio of drug and excipient) was investigated by subjecting the samples to isothermal stress conditions (90 °C for 48 h). A new HPLC method was developed, validated and employed for determining the drug content of the stressed compatibility samples. Results of HPLC revealed that major degradation of bisoprolol fumarate was observed with butylated hydroxyanisole (89.4%), citric acid anhydrous (89%), mannitol (77%) and glycerol (61.9%).

Forced degradation studies, and effect of surfactants and titanium dioxide on the photostability of paliperidone by HPLC.

Forced degradation study of paliperidone under hydrolytic, oxidative, thermal and photolytic stress conditions was conducted using HPLC. The drug was found to be labile under hydrolytic, oxidative and photolytic stress conditions; whereas, it was stable under dry heat stress conditions. Effect of anionic, cationic and non-ionic surfactants applied to the concentration exceeding critical micellar concentration on the photostability of paliperidone was also studied by exposing the samples to sunlight for 72h. Major degradation of the drug was found in presence of cationic and non-ionic surfactants. Effect of titanium dioxide on the photo-degradation of paliperidone in solution state was also studied and it was found that 53% of the drug was degraded after 72h of exposure to sunlight. A common degradation peak was observed in oxidative and TiO2 photocatalysed samples. This peak may be due to the generation of N-oxide of paliperidone. The same degradation peak was also observed in all other photostability samples. Chromatographic separation of drug and its degradation products was achieved on an Alltima C8 (250mm×4.6mm, 5µm) analytical column, using a mobile phase consisting of acetonitrile-ammonium acetate buffer with 0.2% triethylamine (pH 3.5; 20mM) (60:40, v/v) at a flow rate of 1mL/min. Quantification was performed with UV detection at 280nm. The method was validated as per ICH guidelines.