Preparation, Physicochemical Properties, and Structural Characterization of Resistant Starch-Aspirin-Loaded Microspheres.

BACKGROUND Resistant starch is a novel type of dietary fiber that can be considered as a natural polymer carrier with potential development prospects in the field of oral colonic release preparations since it can be degraded by bacteria in the large intestine. MATERIAL AND METHODS In this study, oral resistant starch-drug-loaded microspheres were prepared by spraydrying, and the response surface method was used to optimize the process based on the encapsulation efficiency. RESULTS The optimal preparation process conditions for the resistant starch-aspirin-loaded microspheres were as follows: core material: wall material ratio of 1: 1.98, chitosan solution concentration of 1.98%, and spray drying air inlet temperature of 130.45°C resulted in a reliable entrapment efficiency of 68.96%. Infrared spectroscopy analysis indicated that the encapsulated aspirin-starch microspheres did not differ significantly from the original resistant starch material. The ultrastructure of the drug-loaded microspheres was evenly wrapped with the capsule core and appeared as smooth spheres. The combination of resistant starch, aspirin, and chitosan resulted in a cross-linking reaction that reduced the overall gelatinization temperature compared with the original starch material alone. The light transmittance of the drug-loaded microspheres was slightly higher than that of the original resistant starch, while digestibility was similar to that of the resistant starch, indicating that the release would exist in the environment of the large intestine. CONCLUSIONS This study provides pivotal insights into the development of resistant starch in the field of colonic release preparations.

Tailor-made amino acid-derived pharmaceuticals approved by the FDA in 2019.

Amino acids (AAs) are among a handful of paramount classes of compounds innately involved in the origin and evolution of all known life-forms. Along with basic scientific explorations, the major goal of medicinal chemistry research in the area of tailor-made AAs is the development of more selective and potent pharmaceuticals. The growing acceptance of peptides and peptidomimetics as drugs clearly indicates that AA-based molecules become the most successful structural motif in the modern drug design. In fact, among 24 small-molecule drugs approved by FDA in 2019, 13 of them contain a residue of AA or di-amines or amino-alcohols, which are commonly considered to be derived from the parent AAs. In the present review article, we profile 13 new tailor-made AA-derived pharmaceuticals introduced to the market in 2019. Where it is possible, we will discuss the development form drug-candidates, total synthesis, with emphasis on the core-AA, therapeutic area, and the mode of biological activity.

Large-Scale Asymmetric Synthesis of Fmoc-(S)-2-Amino-6,6,6-Trifluorohexanoic Acid.

Here we report the first large-scale synthesis of Fmoc-(S)-2-amino-6,6,6-trifluorohexanoic acid via asymmetric alkylation of chiral Ni(II)-complex of glycine Schiff base with CF3(CH2)3I. The synthesis was performed on over 100 g scale and can be recommended as the most advanced procedure for reliable preparation of large amounts of enantiomerically pure Fmoc-(S)-2-amino-6,6,6-trifluorohexanoic acid for protein engineering and drug design. Chiral auxiliary used in this protocol can be >90 % recovered and reused.

Effect of substituents on the configurational stability of the stereogenic nitrogen in metal(II) complexes of α-amino acid Schiff bases.

Herein, we report a general method for quantitative measurement of the configurational stability of the stereogenic nitrogen coordinated to M (II) in the corresponding square planar complexes. This stereochemical approach is quite sensitive to steric and electronic effects of the substituents and shown to work well for Ni(II), Pd(II), and Cu(II) complexes. Structural simplicity of the compounds used, coupled with high sensitivity and reliability of experimental procedures, bodes well for application of this approach in evaluation of chemical stability and stereochemical properties of newly designed chiral ligands for general asymmetric synthesis of tailor-made amino acids.