Efavirenz related compounds preparation by hydrolysis procedure: Setting reference standards for chromatographic purity analysis

Correlation between microstructure and bioequivalence in Anti-HIV Drug Efavirenz

“…In general, it is expected that smaller d [4,3] values correspond to higher values of dissolution profile and DE [26], a correlation actually verified for batches 1 and 6, which lay at the two extremes of both size and DE ranges. However, contrary to this expectation, batch 2 shows a higher DE ($70%) than batches 3, 4, and 5, all below 66% (see Table 1).…”

“…A volume of 100 ml water was used as the dispersion medium and the mixture was stirred at 2.000 rpm. This technique provides d [3,2], d [4,3] and the Span values: the former is the surface-weighted mean size, directly related to the surface area; d [4,3] is the volume-weighted mean size, or mass moment mean diameter, whereas Span is a measure of the size distribution width (the narrower the distribution the smaller the Span). The Span definition used in this paper was given by Glover et al [26] as the difference in particle diameters at 10% and 90% of the cumulative volume, d(0.1) and d(0.9) respectively, divided by the volume median diameter d(0.5): Span = [d(0.9) À d(0.1)]/d(0.5).…”

“…Batch 1 presents the lowest value of average particle size. d [4,3] values for batches 2-6 are higher, although still acceptable in a pharmaceutical micronization routine process.…”

“…However, contrary to this expectation, batch 2 shows a higher DE ($70%) than batches 3, 4, and 5, all below 66% (see Table 1). It is important to highlight that, even if the mean particle size of batch 1 (bioequivalent) is smaller than batch 5 (not bioequivalent), the latter has a d [4,3] value well within the acceptable range. Therefore, neither morphology nor particle size characteristics can account for the in vitro differences and in vivo assays.…”

“…Efavirenz (EFV) was approved for the treatment of human immunodeficiency virus type 1 infection (HIV-1) in 1998 [2][3][4]. In the High Activity Antiretroviral Therapy (HAART), it is considered the best choice in the treatment of adults and children [5].…”