Pyrazinamide

The present study was undertaken to determine the forced degradation of Pyrazinamide, performed by various conditions such as acid, alkali, oxidation, thermal and photolytic. The study includes both Pyrazinamide in bulk and tablet formulation. The study based on available guidelines and main reference .Pyrazinamide has a Pyrazine nucleus. It is easily hydrolyzed by acid and alkali. The assay value of degraded products measured by intraday (30mins, 60mins, 90mins) and interday (1st, 3rd, 5th day) by UHPLC. Extensive degradation was observed in alkali hydrolysis method, and the degraded products were analysed by using UHPLC. At 90mins of intraday study using 0.1M NaOH, the degradation assay value of bulk and formulation were found to be 84.50% and 83.40% respectively. Intraday study, the degradation of bulk and formulation was observed on 1st day with the assay value of 23.62% and 25.42% respectively. However complete degradation of Pyrazinamide was observed on 3rd day and 5thday. It was determined that Pyrazinamide was found to be extremely unstable under alkali condition.

Pyrazinamide being a 1st line of defense against tuberculosis is very effective for the first 2 to 3 months of treatment and helps to eradicate a major portion of the strain. But due to its increased use, there are adverse effects such as hepato-toxicity and other dose related side effects. The amount of drug used in formulation is high i.e. 500mg to 1gm. Another major disadvantage is resistance of the bacteria leading to DR-TB (drug resistant tuberculosis). The main objective of this study is to decrease the amount of drug needed for formulation and to avoid hepato-toxicity. Pyrazinamide drug formulation was prepared into a niosomal dosage form by modified ether injection method, using various concentrations of polymer and keeping cholesterol content constant. Characterization was carried out and vesicle size determination showed that the formulated vesicles were in the range of 110-350nm. FTIR results showed that drug and polymers were compatible. Drug content and entrapment efficiency were calculated using UV-spectroscopy at 268nm. In-vitro release studies were carried out for all formulations and it was seen that Span-80 formulation had the highest percentage release when compared to other formulations. The drug release was subjected to various kinetic models and it was observed that all formulations followed zero order kinetics. It can be concluded that all these polymers can be used for the successful formulation of Pyrazinamide niosomes and the surfactant that is most apt was found to be Span-80 in the ratio 1:3 as compared to other polymers in various ratios.