Effects of Diluents on Physical and Chemical Stability of Phenytoin and Phenytoin Sodium.

The focus of the present work was to investigate compatibility between commonly used diluents and the drug (salt and acid form of the phenytoin). Lactose monohydrate (LMH), lactitol hydrate (LCT), and mannitol (MNT) were selected based on commercial products information of phenytoin sodium (PS) and phenytoin acid (PHT). Binary mixtures of the drug-diluent were stored at 60°C and 40°C/75% RH. Similarly, two commercial products, namely Product-A and Product-B, were also investigated in in-use stability. Color of PS-LMH changed from white to yellowish-brown and pH dropped by 3.4 units after 4 weeks exposure. FTIR, XRPD, and NIR chemical images indicated disproportionation in PS-LMH and PS-LCT mixtures stored at 40°C/75% RH. Furthermore, PS-LMH also indicated chemical interactions as indicated by distortion of LMH peaks. PHT-diluent mixture did not exhibit any physical and chemical modifications. Product-A changed color, increased weight, dropped pH value, and exhibited disproportionation and chemical reactions. The dissolution of Product-A decreased from 83.3 ± 1.4 to 7.1 ± 4.4% on 8 weeks exposure to 30°C/75% RH. On the other hand, Product-B did not change; however, dissolution decreased by 15%. In conclusion, PS showed disproportionation and chemical reactions with LMH. Therefore, LMH should be avoided in PS formulations.