Solid-State Stability Profiling of Ramipril to Optimize Its Quality Efficiency and Safety

High global expenditure on out-of-label-date drugs, along with safety concerns associated with the accumulation of degradation impurities, justify the need for stability profiling. In this article, a comprehensive study on the solid-state stability of ramipril (RAM) was performed via isothermal methods under stress conditions. A validated stability-indicating HPLC protocol was used. The effects of various factors on the rate of RAM degradation were investigated, including: temperature, relative air humidity (RH), excipients (talc, starch, methylcellulose and hydroxypropyl methylcellulose), mode of tablet storage, and immediate packaging. The degradation impurities were also identified by HPLC–MS. It was found that RAM was unstable, and temperature accelerated its degradation. RAM was also vulnerable to RH changes, suggesting that it must be protected from moisture. The reaction followed first-order kinetics. The studied excipients stabilized RAM as a pure substance. The tableting process deteriorated its stability, explaining the need for appropriate immediate packaging. RAM in the form of tablets must be stored in blisters, and it cannot be crushed into two halves. The degradation impurities were ramiprilat and the diketopiperazine derivative.

Physicochemical Properties of Poly-vinyl Polymers and Their Influence on Ketoprofen Amorphous Solid Dispersion Performance: A Polymer Selection Case Study

When developing an amorphous solid dispersion (ASD), a prudent choice of polymer is critical to several aspects of ASD performance including: processability, solid state stability and dissolution rate. However, there is little guidance available to formulators to aid judicious polymer selection and a “trial and error” approach is often taken. This study aims to facilitate rational polymer selection and formulation design by generating ASDs using a range of poly-vinyl polymers and ketoprofen as a model active pharmaceutical ingredient (API) and evaluating several aspects of their performance. The molecular weight of the polymer and the ratio of vinyl pyrrolidone to vinyl acetate in the polymer were found to influence the relative humidity at which the relative humidity induced glass transition occurred, as well as the extent of ketoprofen supersaturation achieved during dynamic solubility testing. Interestingly, ASD tablets containing polymers with the vinyl pyrrolidone functional group exhibited higher tensile strengths than those without. This points towards the binder functionality of vinyl pyrrolidone. In conclusion, the physicochemical properties of poly-vinyl polymers greatly influence ketoprofen ASD performance and due regard should be paid to these properties in order to develop an ASD with the desired attributes.

Determination and Data Correlation of Solubility of Sofosbuvir Polymorphs in Ethyl Acetate + Toluene and Methyl tert-Butyl Ether Binary Solvents at the Temperature Range from 268.15 to 308.15 K

A gravimetric method was used to experimentally determine the (solid + liquid) equilibrium of sofosbuvir of crystalline forms A and B in both ethyl acetate + toluene and methyl tert-butyl ether (MTBE) + toluene binary solvents systems at atmosphere pressure. Experiments were carried out at a temperature range of 268.15−308.15 K. Results show that the solubility of sofosbuvir increases with temperature, and the solubility of form B was higher than that of form A. The modified Apelblat model, the CNIBS/Redlich–Kister model, and the combined version of Jouyban–Acree model were employed to correlate the measured solubility data, respectively. Furthermore, an examination of the solid-state stability of the two polymorphs was conducted, finding that form A and form B exhibit good solid-state stability under high temperature, high humidity, and strong light exposure conditions.

Potentiating bisphosphonate-based coordination complexes to treat osteolytic metastases

The phase-inversion hydrothermal synthesis of alendronate and Ca(ii) promotes the formation of a coordination complex whose solid-state, stability, particle size and cytotoxicity were assessed and optimized to potentiate its biomedical applications.

Fluorine-Substituted Arylphosphine for an NHC-Ni(I) System, Air-Stable in a Solid State but Catalytically Active in Solution

Monovalent NHC-nickel complexes bearing triarylphosphine, in which fluorine is incorporated onto the aryl groups, have been synthesized. Tris(3,5-di(trifluoromethyl)-phenyl)phosphine efficiently gave a monovalent nickel bromide complex, whose structure was determined by X-ray diffraction analysis for the first time. In the solid state, the Ni(I) complex was less susceptible to oxidation in air than the triphenylphosphine complex, indicating greatly improved solid-state stability. In contrast, the Ni(I) complex in solution can easily liberate the phosphine, high catalytic activity toward the Kumada–Tamao–Corriu coupling of aryl bromides.