PRİYA SHARMA, RAVNEET KAUR RANA, ARTİ R THAKKAR
Journal of Research in Pharmacy - 2023;27(6):2535-2547
Voriconazole is a well-accepted and effective antifungal agent belonging to BCS class II. Voriconazole is a highly intriguing drug with considerably variable pharmacokinetics among adults and children primarily attributed to the drug-metabolizing enzymes. Additionally, bile salts enhance the absorption of lipophilic drugs in the GI fluids. Since voriconazole has limited solubility, age-related fluctuations in bile salts may affect the drug’s pharmacokinetics. Therefore, the purpose of this study is to assess whether age-associated changes in the GI fluid composition and fluid volume may play a role in affecting the dissolution behavior of voriconazole. Based on that, the solubility and in-vitro dissolution studies of voriconazole were carried out in biorelevant media using 900 ml and 500 ml as GI volumes for adults and pediatrics respectively. Additionally, employing variations in the bile salt concentrations for the dissolution medium to act as a surrogate representing various age-specific cohorts. The results demonstrated that changes in GI volume had a negligible impact on the in-vitro dissolution profiles of voriconazole. However, as anticipated, there were some notable impacts of bile salt changes on the in-vitro dissolution profiles of voriconazole. Furthermore, it can be inferred that other factors, such as variations in the expression and maturation of enzymes, may have a comparatively profound impact on the disparate pharmacokinetics of voriconazole in adults and children besides bile salts alone. Since pharmacopoeial buffers are unable to mimic actual in-vivo conditions, leading to misinterpretation of the results. Therefore, in-vitro dissolution investigations carried out in biorelevant media are preferable.
