The authors focus on the long-term
consistency of dissolution profiles of generic pharmaceutical products. By
analyzing a vast dataset of 1675 products across 127 ingredients, the study
uncovers the intricate factors influencing changes in dissolution profiles
post-approval. It emphasizes the significance of co-development in the increase
of dissimilar dissolution products, the pivotal role of API particle size in poorly
soluble drugs, and the impact of acidic or basic residues on dissolution changes
at specific pH levels. These findings highlight the necessity for proper
development that consider formulation and process variables to ensure the
sustained bioequivalence of generic drugs.
Kopsiyunnanine B was isolated from Yunnan Kopsia arborea and
possesses a unique folded and complex pentacyclic structure containing six
contiguous chiral centers. In this article, the authors reported the asymmetric
total synthesis of Kopsiyunnanine B, along with their originally proposed
biosynthetic pathway. The key transformation is an impressive cascade reaction
that constructs three ring structures and three chiral centers in one step.
Following the stereoselective reduction of the β-acrylate and oxidation to
oxindole, the natural product is synthesized over 14 steps. Their careful
consideration of the biosynthetic hypothesis has resulted in an exceptionally
efficient synthesis with a minimal number of steps.
Given
the spread of antimicrobial-resistant bacteria (AMR), there is an urgent need
for the ongoing search for novel antibacterial natural products. The authors discovered
five new viridogrisein congeners from Streptomyces niveoruber with potent
antibacterial activities against Gram-positive bacteria. Additionally,
co-treatment with griseoviridin, another natural product from the same producer,
enhanced the activity. Biosynthetic studies have revealed that SgvY, encoded in
the viridogrisein biosynthetic gene cluster, detoxifies viridogrisein against Staphylococcus
aureus by linearization, suggesting its role in the self-resistance system
in S. niveoruber. These results could facilitate the understanding of antimicrobial-resistant
mechanism for developing the countermeasures against AMR.
The
Kawakita equation has been used for estimating yield pressure and porosity of
compressed powder in the die. This equation assumes the compression pressure is
homogeneously distributed. However, in actual powders, it is not homogeneously
distributed due to the friction on the die wall. The authors extended the
Kawakita equation by accounting for the inhomogeneous distribution of
compression pressure. The extended Kawakita equation theoretically explained
the powder behavior yielding sequentially from the loading punch to fixed punch
due to the spatial limitation of particle rearrangement. Therefore, the
extended Kawakita equation advances understanding of powder compaction in die.
While the addition of cellulose
nanofiber (CNF) to tablet formulations during direct compression has attracted
increasing attention as a means for enhancing tablet strength and
disintegration, they are also known to increase the variation in tablet weight
and drug content. This study evaluated the effect of pulverized CNF on the
variation in tablet weight and drug content. The pulverized CNF reduced both
weight and drug content variation to a larger extent than untreated CNF.
Further, either CNF achieved sufficient tablet strength and short
disintegration time. Thus, the authors provided evidence that CNF is useful as
a multifunctional additive.
Computational
screening is a powerful technique for drug discovery today. In this work, a virtual
screening was performed to find SARS-Cov-2 PL protease inhibitors, utilizing a
chemical database consisting of approved and investigational drugs. A key issue
for successful virtual screening is the accuracy of computational predictions
for the binding pose and score of each compound to the target. The authors
applied their original software program, Chem. Pharm. Bull., 2017, 65, 461, for
calculating the score. Their approach identified five inhibitory compounds
against the PL protease. The inhibitory activities were evaluated by an
enzymatic assay with the FRET technique.