The measurement and control of high-risk host cell proteins for polysorbate degradation in biologics formulation

Non-ionic surfactant polysorbates (PS), including PS-80 and PS-20, are commonly used in the formulation of biotherapeutic products for both preventing surface adsorption and acting as stabilizer against protein aggregation. Trace levels of residual host cell proteins (HCPs) with lipase or esterase enzymatic activity have been shown to degrade polysorbates in biologics formulation. The measurement and control of these low-abundance, high-risk HCPs for polysorbate degradation is an industry-wide challenge to achieve desired shelf-life of biopharmaceuticals in liquid formulation, especially for high-concentration formulation product development. Here, we reviewed the challenges, recent advances and future opportunities of analytical method development, risk assessment and control strategies for polysorbate degradation during formulation development with a focus on enzymatic degradation. Continued efforts to advance our understanding of polysorbate degradation in biologics formulation will help develop high-quality medicines for patients.

Effects of Different Irradiation Treatments on Total Saponins Content of Sapindus mukorossi

Sapindus mukorossi Gaertn is also known as Mu Huanzi, You Huanzi, soap tree, etc. The pericarp of Sapindus mukorossi contains many saponins, which is a type of natural non-ionic surfactant. Its extract has vigorous surface activity and biological activities such as bacteriostasis, oxidation resistance, and free radical scavenging. The Sapindus mukorossi extract is an environmentally friendly washing product that microorganisms can be rapidly decompose in nature without any environmental pollution.This study aims to investigate the effects of E-beam and Co60-γ irradiation on the total saponins content in the crude extract of the S mukorossi. The S mukorossi powder is irradiated with E-beam and Co60-γ ray at doses of 0, 4, 6, 8, 10, and 12 kGy for E-beam and 0, 50, 100, 150, and 200 Gy, respectively, for Co60-γ ray. The changes in the content of total saponins in the crude extract, total detergency, and the bacteriostatic abilities before and after the irradiation were analyzed. The results showed that the content of total saponins in samples irradiated by E-beam was significantly higher than that in non-irradiated samples. The saponins yield was the highest at a radiation dose of 6 kGy, and the detergency and bacteriostatic ability were also the strongest. After low-dose Co6-γ irradiation, the total saponins in the S mukorossi crude extract, and detergency and bacteriostatic ability had no apparent change. Conclusion: E-beam irradiation at a dose of 6 kGy can effectively improve the content of total saponins in the crude extract of S mukorossi powder. In addition, its effects on detergency and bacteriostatic abilities are relatively significant. The findings provide sufficient reference data for the further development of S mukorossi commodities.

FORMULATION AND DEVELOPMENT OF PRONIOSOMAL GEL FOR TOPICAL DELIVERY OF AMPHOTERICIN B

Objective: The present research work of Amphotericin B Proniosomal gel focuses on improving patient compliance by reducing the side effects of conventional intravenous injections and minimizing the problem of physical stability and to localize drug at site of action. Methods: Proniosomal gels are prepared by coacervation phase separation technique using different concentration of non-ionic surfactants (Span and Tween) for uniform vesicle formation, lecithin as permeation enhancer/membrane stabilizer and cholesterol as a vesicle cement providing prolonged release. Prepared gels were evaluated for their viscosity, pH, spreadability, entrapment efficiency, drug content uniformity, extrudability, in vitro drug release, permeability and stability studies. Results: Among the nine formulations, F2 (containing 10 mg drug, 250 mg Span 60, 50 mg Soya lecithin) was found to be promising. Fourier Transform infra-red (FT-IR) spectra studies represented no interaction and physicochemical characteristics were found within the limits. The percentages of drug content and entrapment efficiency were determined to be 95.16%±0.40 and 94.20%±0.20, respectively. In vitro drug release was about 95.72%±0.30. Conclusion: Proniosomal gel could constitute a promising approach for topical delivery of Amphotericin B by encapsulating it in non-ionic surfactant to provide patient compliance with cutaneous fungal infection, which was found to be safe, tolerable and efficacious.

Improvement of acid treatment with the sintanol preparation after hydro-sand blasting of wells in the conditions of ANK «Bashneft»

A sandblasting hammer is lowered into the well, setting against the selected processing interval, and hydraulic clamps are necessary for the rig to be held firmly. The displacement of the latter eliminates the possibility of selective processing. After the usual sandblasting and flushing the well from sand, without changing the position of the perforator, an acid solution is pumped into the pipes, which, entering the channel formed, is filtered through its walls into the treated section of the formation. The part of the acid that, after the end of the treatment, has accumulated in the wellbore, is forced into the reservoir by the squeezing fluid through the annular space. Increase the acid depletion time, i.e. slow down the reaction rate by adding special reagents to the solution. So, a syntanol DS-10 TU 2483-016-71150986-2012 (a non-ionic surfactant and is intended for use as an effective surfactant) is a very effective reaction rate reducer. Adding it in an amount of 0.5% (by weight of the volume of the solution) can reduce the reaction rate by 2.7 times. Keywords: speed; reaction; syntanol; processing; pressure.

Liquid-liquid phase separated microdomains of an amphiphilic graft copolymer in a surfactant-rich medium

The liquid-liquid phase separation (LLPS) of amphiphilic thermoresponsive copolymers can lead to the formation of micron-sized domains, known as simple coacervates. Due to their potential to confine active principles, these copolymer-rich droplets have gained interest as encapsulating agents. Understanding and controlling the conditions inducing this LLPS is therefore essential for applicative purposes and requires thorough fundamental studies on self-coacervation. In this work, we investigate the LLPS of a comb-like graft copolymer (PEG-g-PVAc) consisting of a poly(ethylene glycol) backbone (6 kDa) with 2-3 grafted poly(vinyl acetate) chains, and a PEG/PVAc weight ratio of 40/60. Specifically, we report the effect of various water-soluble additives on its phase separation behavior. Kosmotropes and non-ionic surfactants were found to decrease the phase separation temperature of the copolymer, while chaotropes and, above all, ionic surfactants increased it. We then focus on the phase behavior of PEG-g-PVAc in the presence of sodium citrate and a C14-15 E7 non-ionic surfactant (N45-7), defining the compositional range for the generation of LLPS microdomains at room temperature and monitoring their formation with fluorescence confocal microscopy. Finally, we determine the composition of the microdomains through confocal Raman microscopy, demonstrating the presence of PEG-g-PVAc, N45-7, and water. These results expand our knowledge on polymeric self-coacervation, clarifying the optimal conditions and composition needed to obtain LLPS microdomains with encapsulation potential at room temperature in surfactant-rich formulations.

Study of the stability of lipid nanoemulsions with oleic acid

This work presents the results of a study on the effect of ionic surfactant cetriltrimethylammonium chloride (CTAB) on the size and ζ-potential of lipid nanoemulsions composed of oleic acid, prepared by temperature phase inversion method and stabilized by nonionic surfactants — Tween 60, Span 60

Glutathione-loaded non-ionic surfactant niosomes: A new approach to improve oral bioavailability and hepatoprotective efficacy of glutathione

A new formulation (niosomes) was prepared to enhance the bioavailability, hepatic tissue uptake, and hepatoprotective activity of glutathione (GSH). The GSH-loaded niosomes (nanoform, N-GSH) were formulated by the thin-film hydration technique using cholesterol/non-ionic surfactants (Span®40, Span®60, and Tween®80) at a componential ratio of 1:1 and 2:1. The hepatoprotective activity of N-GSH, GSH, and the standard silymarin against CCl4-induced liver damage and oxidative stress were tested on the rats’ model. The hepatic morphology and histopathological characters were also investigated. The tissue contents of N-GSH were analysed using a concurrently validated RP-HPLC method. The optimized niosomes, composed of glutathione (500 mg), cholesterol, and Span®60-Tween®80 at a molar ratio of 2:1 of cholesterol/non-ionic surfactant, displaying a particle size of 688.5 ± 14.52 nm, a zeta potential of −26.47 ± 0.158 mV, and encapsulation efficiency (EE) of 66 ± 2.8% was selected for in vivo testing. The levels of MDA, NO, SOD, NF-κB, IL-1β, and Bcl-2 were measured. The results demonstrated that hepatic tissue damage was ameliorated using N-GSH as confirmed by the morphological and histopathological examination compared to the CCl4 and control groups. The N-GSH significantly (p < 0.05) decreased the elevated levels of hepatic enzymes, oxidative parameters, and inflammatory mediators, as compared to silymarin and GSH. Also, N-GSH significantly (p < 0.05) increased GSH hepatocyte concentrations as compared to the control groups. The present study demonstrated that N-GSH remarkably improved glutathione oral bioavailability and hepatic tissue uptake, thereby introducing a new glutathione formulation to protect hepatic tissue from injury and restore its GSH contents.