Comparison of In Vitro and Dissolution of Norvir Oral Powder: Relevance of a too Rapid Dissolution Test.

Objectives: Norvir oral powder [ritonavir (RTV)] employs polyvinylpyrrolidone/vinyl acetate as the polymer to formulate an amorphous solid dispersion. Its oral absolute bioavailability is 70% in the fasted state, and it has negative food effects. The aim of this study was to perform in vitro dissolution of Norvir powder and Wagner-Nelson deconvolution of data under fasted, moderate fat, and high fat conditions in order to elucidate the relevance of dissolution testing.

Materials And Methods: dissolution of Norvir oral powder was conducted, and the human pharmacokinetic data of Norvir powder were obtained from literature, under fasted, moderate fat, and high fat conditions. Wagner-Nelson deconvolutions were performed. The absolute fraction absorbed (F) profiles were compared to the dissolution (F) profiles. Levy-Polli plot analysis was also conducted. For each pharmacokinetic condition, a scale factor was estimated to approximate the extent to which dissolution needed to be slowed down to mimic dissolution.

Results: Qualitatively, there was a large difference between and dissolution. dissolution showed 98% release in 5 minutes. Meanwhile, from Wagner-Nelson analysis, only 5.5% of the drug dissolved (and absorbed) in 5 min under fasted conditions. It was not until 2 hr that 49% of the RTV dose dissolved (and was absorbed) . , moderate fat and high fat conditions were even slower in producing a certain effect. The Levy-Polli plot exhibited a "reverse-L" profile. It was concluded that such rapid dissolution did not mimic the dissolution of RTV.

Conclusion: Biopharmaceutic consideration of dissolution, pharmacokinetics, and deconvolution analysis indicated that dissolution was "too rapid" to adequately mimic dissolution. Findings suggest greater inspection of methods for poorly water-soluble drugs, especially those drugs where absorption is expected to be rate-limited by dissolution.