Development and Validation of Stability Indicating RP-HPLC Method for the Determination of Process and Degradation-Related Impurities in Sugammadex Sodium Drug Substance

The aim of this study is to develop and validate a sensitive and specific stability-indicating reversed-phase high-performance liquid chromatographic (RP-HPLC) method for the quantitative determination of Sugammadex sodium together with its process and possible degradation impurities. The pKa value is 2.82. The chromatographic conditions have been optimized by the Hypersil Gold 250 mm X 4.6 mm, 3 µ RP-18 columns with gradient elution using a mobile phase composed of 0.1% phosphoric acid, acetonitrile, and methanol. The eluents were monitored at 205 nm with a flow rate of 1.0 mL/min with an injection volume of 20 µL. The optimized method produced symmetrical and sharp peaks with good separation between the process and degradation impurities. The forced degradation study was carried out under acid, base, oxidation, and thermal conditions to demonstrate the stability-indicating capability of the method. The method was validated as per the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2 (R1) and showed excellent specificity, precision, linearity, accuracy, and robustness. The developed HPLC method was precise with a value of 0.25%. The relative standard deviation of accuracy represented by the recovery studies ranged between 89.5% and 104.6%. Linearity analyses indicated a correlation coefficient value of greater than 0.996 for Sugammadex and its known impurities. The LOD and LOQ values for Sugammadex ranged from 0.017% to 0.050%, and for its related impurities, they ranged from 0.015% to 0.055%. The stability of the analytical solution was evaluated and was stable for 75 h when stored at 5 °C. No chromatographic interference was observed during the degradation studies and also in the blank chromatogram.

     

Lighting the Path: Light Delivery Strategies to Activate Photoresponsive Biomaterials In Vivo

Photoresponsive biomaterials are experiencing a transition from in vitro models to in vivo demonstrations that point toward clinical translation. Dynamic hydrogels for cell encapsulation, light-responsive carriers for controlled drug delivery, and nanomaterials containing photosensitizers for photodynamic therapy are relevant examples. Nonetheless, the step to the clinic largely depends on their combination with technologies to bring light into the body. This review highlights the challenge of photoactivation in vivo, and presents strategies for light management that can be adopted for this purpose. The authors’ focus is on technologies that are materials-driven, particularly upconversion nanoparticles that assist in “direct path” light delivery through tissue, and optical waveguides that “clear the path” between external light source and in vivo target. The authors’ intention is to assist the photoresponsive biomaterials community transition toward medical technologies by presenting light delivery concepts that can be integrated with the photoresponsive targets. The authors also aim to stimulate further innovation in materials-based light delivery platforms by highlighting needs and opportunities for in vivo photoactivation of biomaterials.     

Effect of the Twisting Motion on the Nonunifornities of Transmyocardial Fiber Mechanics and Energy Demand A Theoretical Study

The contraction of the left ventricle (LV) is manifested by a distribution of strains and strain rates throughout the muscle thickness. Using a nested shell spheroidal model of the LV, which accounts for a fiber angle distribution from + 60°at the endocardium to ?60° at the epicardium, and the radial electrical activation pattern from the endocardium to the epicardium, it can be shown that endocardial layers undergo higher strains than the epicardial layers throughout the cardiac cycle, and higher length changes characterize the endocardial sarcomeres relative to the epicardial sarcomeres. However, the calculated nonuniformities in the sarcomeres' shortening are significantly moderated when the physiological twisting motion of the LV around the longitudinal axis is accounted for. Thus, the twisting motion of the heart is a basic mechanism by which the sarcomere function is maintained within its physiological range.     

Buffering packetised data: an examination of the crossover effect

Buffer analysis has traditionally relied heavily on the use of traffic models with short range (exponentially decaying) autocorrelation, e.g. Poisson and Markov modulated Poisson processes. Recent literature has suggested the presence of traffic with slowly (hyperbolically) decaying autocorrelation functions; these sources collectively and individually seem to be exhibiting the phenomenon of long range dependence (LRD). Furthermore, it has been claimed that this sort of traffic may exhibit behaviour, when buffered, that is advantageous in that a smaller buffer may be required than would be the case with non-LRD traffic. This phenomenon has been named the crossover effect, and the authors quantify its relevance to ATM networking, using simulation studies of a homogenous mix of chaotic sources. These show that there is a crossover effect, but the key finding is that this effect is much nearer to a buffer length of zero than was predicted by previous theoretical studies, actually occurring at a value so low that it has no practical significance     

A quasiconformal dynamic property of the disk

It is known that every conformai embedding of the disk into the extended complex plane possesses a r²-quasiconformal extension across eachr-level line (the r²-property of a domain). We show here that this is a characteristic property of the disk: any simply connected domain which is not a disk does not admit ther ²-property. Supported by the RiP-program of the Volkswagen-Stiftung in the Mathematisches Forschungsinstitut Oberwolfach.     

Skew Models II

If g and G are the pdf and the cdf of a distribution symmetric around 0 then the pdf 2g(u)G(λ u) is said to define a skew distribution. In this paper, we provide a mathematical treatment of the skew distributions when g and G are taken to come from one of Pearson type II, Pearson type VII or the generalized t distribution.