Pharmaceutical Industry Research Articles

Physicochemical and processing properties and in vitro fecal fermentation characteristics of Prunus cerasifera Ehrhart polysaccharide

Prunus cerasifera Ehrhart fruit polysaccharide (PCP) was obtained after determining the optimal extraction conditions for complex enzyme-assisted hot buffer extraction based on single-factor experiments and response surface methodology, followed by characterization of its physicochemical, processing, rheological, and biological properties. PCP was a thermally stable carbohydrate with acidic functional groups and a molecular weight of 1398.69 kDa, exhibiting smooth, dense flake and honeycomb network microstructures. PCP had favorable hygroscopicity, moisturizing properties, water and oil-holding capacity, proemulsification capability, and in vitro antioxidant activity. The apparent viscosity of PCP in an aqueous system was dependent on concentration and temperature and was altered by the variety and amount of metal ions added; its aqueous solutions exhibited strong viscosity and hydrogel-forming tendencies at suitable concentrations, along with excellent hydrogel properties after gelation. Furthermore, PCP favored the growth of beneficial gut microbiota and associated microbes responsible for producing essential short-chain fatty acids. Overall, PCP displayed high potential as a multifunctional additive for applications in the food, pharmaceutical, and cosmetic industries.

Degradation of (1→3)(1→6)-α-D-dextran by ultrasound: Molecular weight, viscosity and kinetics

The (1→3)(1→6)-α-D-dextran (alternating dextran) produced by Leuconostoc citreum SK24.002 is a novel functional exopolysaccharide, and its low molecular weight derivatives have potential applications in the food, pharmaceutical, and chemical industries. In this work, we used sonication, a green polysaccharide disruption method, to study the degradation process of this dextran by changing the intensity and duration of the sonication treatment and the concentration of the dextran solution. The molecular weight and viscosity of the dextran products were measured with a high-performance size exclusion column chromatography–multi-angle laser light scattering–refractive index system and by rheometry, respectively. The degradation efficiency of dextran was directly affected by the duration and intensity of the ultrasonic treatment and the concentration of the dextran solution. The polydispersity index fluctuated as the duration of the sonication treatment increased. The combination of a high intensity (672 W/cm2) and long (120 min) sonication treatment and a low solution concentration (3 g dextran/100 mL) was most effective for reducing the apparent and complex viscosities of dextran. The storage modulus of dextran was always slightly larger than its loss modulus, indicating that it formed a gel-like structure. The second-order kinetic model (1/Mwt - 1/Mw0 = kt) was the best fit to explain the degradation dynamics of dextran by sonication at intensities of 168 W/cm2–834 W/cm2 and with dextran solution concentrations of 1 g/100 mL – 7 g/100 mL. Our findings show that sonication is an effective way to reduce the molecular weight of alternating dextran.

Melanoma-on-a-chip model for anticancer drug injecting delivery method

The pharmaceutical and cosmetic industries are encountering a challenge in adopting new study models for product development. there has been a growing interest in organ-on-a-chip systems, and particularly for generating skin models. While numerous alternatives replicating high-fidelity skin models exist, there is a notable absence of melanoma study's methodology specifically on these microfluidic chips. This work introduces a novel skin-on-a-chip device featuring two microfluidic chambers, facilitating a 3D cell co-culture involving fibroblasts, keratinocytes, and melanoma cells. The design of this organ-on-a-chip has enabled the administration of the anticancer treatment Gemcitabine using an injection system within the chip. The results of this work have shown a significant impact on the co-culture distribution of cells, decreasing the population of cancerous cells after the administration of Gemcitabine. The work presented in this article demonstrates the effectiveness of the chip and the administration method for testing anti-melanoma therapies and position this technology as an enhanced fidelity model for studying melanoma while providing an alternative for real-time monitoring of drug testing.

PHYSICOCHEMICAL AND SPECTROSCOPIC ANALYSIS OF INTERACTIONS BETWEEN ASPIRIN AND NORMAL SALINE AT DIFFERENT TEMPERATURES

The primary goal of the current investigation is to explore the molecular interactions between the aspirin (2-Acetoxybenzoic acid) and normal saline (0.9% w/v aqueous NaCl) at various concentrations (0.001–0.010) m and temperature (T= 300.15–315.15) K. To understand the various possible molecular interactions, volumetric, acoustic, conductometric and viscometric parameters were evaluated using experimental measured values of densities (ρ), ultrasonic velocities (u), specific conductance (κ), and viscosities (η). The results derived from these parameters have been examined in terms of drug–solvent and drug-drug interactions. The results of physicochemical studies indicate that aspirin exhibits strong interactional and structure–forming behaviour in normal saline. These results were well supported by UV-visible spectral studies which indicate the existence of intense aspirin–normal saline interactions in the form of modification in absorption maximum and absorption wavelength. The cyclic voltammetric studies were also performed to explore the oxidation/reduction behaviour and effect of aspirin on hemolysis. The experimental analysis of these studies provides valuable insights for better drug design, drug delivery, compatibility, potential safety, and biological relevance for the pharmaceutical and health industries.

Hybrid nano-biocomposite based on polysaccharide and graphene oxide for the practical separation of proteins in a fixed bed adsorption column

Proteins and amino acids are essential to humans and all living beings. Moreover, these compounds are present in the pharmaceutical, food, and cosmetic industries. Proteins need to be purified for use in industry. This work aims to synthesize and apply a nano-biocomposite based on graphene oxide (GO) and agar (polysaccharide) for protein separation and purification. The hydrogel composite was tested for myoglobin (Mb) adsorption, the effect of changing the initial pH in Mb adsorption, and the ionic strength was evaluated. The adsorptive capacity values were higher at pH=5 and 6 and decreased at higher pH values. The increase in NaCl concentration did not affect the adsorptive capacity significantly. The composite exhibited a notorious value of maximum experimental adsorption capacity in the equilibrium of over 790 mg g−1 at pH=5 and 25 °C. As GO interacts with the polymeric agar matrix, resulting in a 3D material, the material developed could adsorb Mb in a fixed bed column and single and binary (BSA+Mb) systems. There are indications that the GO-based composite possibly forms a complex with the peptide ligands of myoglobin, forming a protein corona, making Mb desorption difficult.

A Comprehensive Evaluation of Chemical, Bioactive Profile, and Anti-oxidant Potential of Gabiroba (Campomanesia cambessedeana): An Underexplored Fruit from Brazil

Background: The Cerrado region has one of the world's largest and most diverse tropical biodiversity, hosting several species of exotic fruits little explored. In this context, we can highlight the gabiroba (Campomanesia cambessedeana), a native fruit tree belonging to the Myrtaceae family. However, its fruits are not used frequently, except by the local population who consume them, and are also reported as nutritional. Objective: This work evaluated the chemical composition of the whole fruit, pulp, peel, and seed of gabiroba. Methods: Physicochemical characterization, bioactive compounds and antioxidant potential, and mineral profile (ICP-OES) were evaluated. Individual phenolic compounds and organic acids by liquid chromatography (HPLC-DAD) of the pulp, peel, and seed fractions of gabiroba were also explored. Results: The results showed that the gabiroba fruit has a low lipid content (1.09 g 100 g-1), high magnesium content (12.60 μg g-1), and significant values of total phenolics (153.17 mg EAG 100 g-1), vitamin C (51.20 mg AA 100 g-1) and antioxidant potential by DPPH radical scavenging (15.35 g sample g-1 DPPH). The analysis of organic acids showed that the pulp and peel are rich in malic acid (7.29 and 8.15 mg 100 g-1, respectively) and the seed in citric acid (10.26 mg 100 g-1). On the other hand, both pulp, peel, and seed fractions showed similar individual phenolic composition, mainly being composed of catechin (3.36, 2.71, and 2.70 mg 100 g-1), gallic acid (1.67, 1.66, and 1.68 mg 100 g-1) and rutin (0.85, 1.39 and 1.16 mg 100 g-1, respectively). Conclusion: The individual phenolics in the gabiroba fractions may have been responsible for the high antioxidant activity. In this way, gabiroba has demonstrated its technological potential for its full use in producing food products and applications in the pharmaceutical and cosmetics industry.

A Review on Silver Nanoparticles: Synthesis Approaches, Properties, Characterization and Applications.

Nanoparticles are a significant topic due to their applications in various fields, including biology, optics, catalysis, pharmaceutics, health, agriculture, and industry, with biosynthesis processes being quick, easy, and environmentally friendly. Due to their applications across multiple industries, silver nanoparticles, or AgNPs, have become the most desired nanoparticles with the recent development of nanotechnology. The physical, chemical, and biological characteristics of AgNPs are being studied. These characteristics are crucial for limiting the hazards associated with silver nanoparticles while optimizing their potential applications in many fields. A higher degree of toxicity in both the environment and living things could arise from the increasing use of silver nanoparticles in the product. Silver nanoparticles find application in wound care, anti-infective therapy, food, pharmaceutical, and cosmetic industries. As antioxidant, antiviral, anticancer, antifungal, antiinflammatory, and microbiological agents, silver nanoparticles are widely used. Not only must the particles be nanoscale in order for silver nanoparticles to be present, but their production must also be simple and inexpensive to achieve. This paper aims to review the different methods of synthesis of silver nanoparticles, properties, characterization, and their applications. In specific, several chemical and green synthesis approaches for synthesising silver nanoparticles have been discussed. The morphology, size, thermal properties, toxicity properties, electrical properties, catalytic properties, and applications of silver nanoparticles are focused. The main focus is on the effective and efficient synthesis of pure silver nanoparticles and their potential applications.

From molasses to purified α-ketoglutarate with engineered Corynebacterium glutamicum

α-ketoglutarate (AKG) is a valuable dicarboxylic acid with multiple applications in the food, pharmaceutical and chemical industries. Its chemical synthesis is associated with toxic by-products, low specificity and high energy input. To create a more environmentally friendly and sustainable alternative, a microbial production process for AKG was developed. Four potential producer strains were generated by metabolic engineering of Corynebacteriumglutamicum and characterized on defined glucose/sucrose media as well as molasses, a side stream from sugar beet processing. While strain C.glutamicum PO6-iolT1Δgdh ΔgltB mscCG’ ΔodhA was not able to grow on defined media it outperformed all predecessor variants on molasses. Successful scale-up into a fed-batch bioreactor process with molasses yielded 96.2 g AKG with a conversion yield of 0.64 gg−1. Finally, downstream processing by liquid–liquid extraction with ethyl acetate enabled product purification with an extraction efficiency of 87 % and an AKG purity of > 93 %.

One-pot multicomponent photo-induced eosin-Y catalyzed synthesis of 2-amino oxa/thiazine derivatives

An effective and advantageous one-pot multicomponent photo-induced methodology has been developed for the synthesis of biologically potent 2-amino-4H-1,3-oxa/thiazine from substituted benzaldehyde, ethynylbenzene and urea/thiourea catalyzed by eosin-Y at room temperature using EtOH as a green solvent with wide range of applications in pharmaceutical and agriculture industries. This proposed work emphasizes to investigate an accessible, safe, easy and convenient method for the synthesis of 2-amino oxa/thiazine derivatives with good to excellent yield.

Modeling, Simulation, and Optimization of Multi-Stage Equilibrium Extraction of Phenolic Compounds from Grape Pomace

The seasonal nature of wine production results in the accumulation of significant quantities of grape pomace (GP) during harvest, presenting management challenges for wineries that traditionally regard this solid byproduct as low-value waste. However, extracting phenolic compounds (PCs) from GP offers a promising avenue for creating bioactive extracts for use in the food, pharmaceutical, and cosmetic industries. This study develops a mathematical model for predicting the total phenolic content (TPC) and total dissolved solids (TDS) in liquids obtained from multi-equilibrium-stage extraction processes using a 50% aqueous ethanol solution to recover PCs from Tannat GP. The model is applicable across a wide range of TPC and TDS concentrations in the liquid (0.2-45.4 gGAE/L for TPC and 1 to 118 g/L for TDS) and extraction temperatures between 30 and 70 °C. It is used to determine the optimal operational conditions of a Shanks extraction system, either to minimize fresh solvent consumption or to maximize selectivity for PCs extraction, achieving a desired extraction yield with a specified number of extraction vessels.

The effect of water on the crystallization of phytosterols and phytostanols in organic solutions

Phytosterols (C29H50O), also known as plant sterols and stanols, are valuable biomolecules with a variety of applications in the pharma, food, and cosmetics industries. Phytosterols are typically manufactured from vegetable oil and tall oil feedstocks through a cooling crystallization process. Depending on the feedstock used, the composition regarding individual phytosterols and phytostanols (saturated analogs of phytosterols), also varies to a large extent. In the current research it was observed that by adding a small amount of water to the organic solvent [i.e., n(water)/n(acetone) of 0.17, n(water)/n(ethanol) of 0.13, and n(water)/n(ethyl acetate) of 0.10], the final phytosterol profile regarding phytosterol and phytostanol concentrations can be modified. This can be explained by the different solubility behavior of phytosterols and phytostanols in the studied solvent systems, based on experimental results obtained from transmissivity measurements. Phytostanols have surprisingly low solubility when compared to phytosterols in all the studied solvent systems. However, in the presence of water, phytosterol solubility decreased more compared to phytostanols. To the best of our knowledge, this is the first time that phytostanol solubility has been systematically studied. Moreover, phytosterol and phytostanol concentrations in a crystallized product with varying binary solvent systems containing water has not previously been reported. The measured experimental solubility data correlated well with the studied solubility models (van't Hoff, modified Apelblat, Buchowski-Ksiazaczak (λh), and polynomial equations). Understanding the solubility behavior of phytosterols and phytostanols allows to optimize the crystallization process itself toward a broader raw material selection, and better yield and quality in the production of phytosterols from plant-based raw materials. In addition, these findings can potentially be further utilized in phytosterol formulations for various applications.

Accelerating pharmaceutical tablet development by transfer of powder compaction equipment across types and scales

Roller compaction is a key unit operation in a dry granulation line for pharmaceutical tablet manufacturing. During product development, one would like to find the roller compactor (RC) settings that are required to achieve a desired ribbon solid fraction. These settings can be determined from the compression profile of the powder mixture being compacted and a mathematical model that interprets it. However, establishing compression profiles in an RC requires relatively large amounts of powder, which are expensive and may not be available during drug development. As a cost-effective alternative to an RC, a compactor simulator (CS) can be used, which is a small-scale equipment that uses minimal amounts of powder to build the compression profile. However, since the working principles of a CS and an RC are different, the compression profiles obtained from the two devices for a given powder are also different. In this study, we propose a transfer learning approach that allows the RC compression profile of a given powder to be easily predicted from the compression profile obtained in a CS for the same powder. Based on the well-known Johanson model and on the mass correction factor theory, we examine the compaction behavior of six formulations, two of which including active ingredients, and we find that the mass correction factor does not depend significantly on the powder being compacted. We develop a simple, generalized correlation (transfer model) that allows the mass correction factor to be predicted solely as a function of the pressure at which the compaction is carried out. By using the proposed transfer model, the prediction of the RC compression profiles for the validation powders is significantly improved over the case where a constant value of the mass correction factor is used.

Interconnected influence: Unraveling purdue pharmaceutical's role in the global response to the opioid crisis

BackgroundThe global pharmaceutical industry has a long history of prioritizing profits over public health through widespread practices such as price gouging, deceptive marketing, and fraud. A prominent example of this issue is the mislabeling and mass-marketing of OxyContin by Purdue Pharmaceuticals (Purdue) that catalyzed the opioid crises in and beyond the United States. MethodsGuided by Actor-Network Theory, this case study employs Visual Network Analysis to map the actors-networks involved in responding to the harms caused by Purdue. Data was generated from peer-reviewed and grey literature published between 2007 and 2022 (n = 40) and imported into Gephi visualization software where centrality metrics were applied. ResultsA total of 39 actors and 99 relationships were visualized based on the relational thinking that actors who are heavily interconnected with others are rendered important. Centrality measures identified the socio-technical centrality of Purdue in influencing the response to the harms it caused. Purdue exerted influence through various avenues, most prominently through the creation and cooptation of pain advocacy groups, their close ties with United States elected officials, and through embedding pro-opioid messaging in international guidance documents. In doing so, Purdue was able to extend the reach and impact of their opioid promotion, while simultaneously limiting the capacity of regulatory bodies to pursue accountability and implement policies to mitigate opioid-related harms. ConclusionThis study advances understandings of the complex interplay between transnational pharmaceutical companies, global health systems, regulatory bodies, and public health. In doing so, we underscore the need for stronger regulation and increased transparency surrounding the interactions between pharma, patient groups, governments, and international organizations to better address and prevent future harms.

Research and development investment of Chinese chemical pharmaceutical companies under the national pooled procurement: a retrospective panel data analysis, 2013–2022

ObjectiveTo generate evidence about changes in the research and development (R&D) investment of Chinese chemical pharmaceutical companies before and after the implementation of the national pooled procurement, to respond to...

Pharma innovation: how evolutionary economics is shaping the future of pharma R&D

This paper describes the theory of evolutionary economics in the context of pharmaceutical R&D. In this context, the R&D productivity crisis acts as a key selection mechanism, and R&D, technology and industry trends provide mechanisms of variation. Drawing on today’s prevailing business model among leading pharmaceutical companies, the biotech-leveraged pharma company (BIPCO), I propose two new value creation logics: the technology-investigating pharma company (TIPCO) and the asset-integrating pharma company (AIPCO). Although some companies already share aspects of these business models, it is not yet clear, in terms of evolutionary economics, what the ultimate outcome of the evolutionary process in pharma R&D will be.

Medical Science Liaisons: A Guide for Advanced Practice Registered Nurses

Medical science liaisons (MSLs) are part of the field medical affairs (FMA) department of pharmaceutical companies and are scientific resources for advanced practice registered nurses (APRNs). Following strict regulations and antikickback statutes, MSLs operate differently from sales and engage in unbiased, nonpromotional scientific exchange to provide clinical resources to APRNs. They also collaborate with shareholders like professional organizations, clinical trial sites, and academic institutions. Understanding MSL engagement allows APRNs multiple avenues both externally and within the pharmaceutical industry to leverage their experience to enhance clinical practice.

Recombinant Antibody Fragments for Neurological Disorders: An Update.

Recombinant antibody fragments are promising alternatives to full-length immunoglobulins, creating big opportunities for the pharmaceutical industry. Nowadays, antibody fragments such as antigen-binding fragments (Fab), single-chain fragment variable (scFv), single-domain antibodies (sdAbs), and bispecific antibodies (bsAbs) are being evaluated as diagnostics or therapeutics in preclinical models and in clinical trials. Immunotherapy approaches, including passive transfer of protective antibodies, have shown therapeutic efficacy in several animal models of Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), Huntington's disease (HD), transmissible spongiform encephalopathies (TSEs) and multiple sclerosis (MS). There are various antibodies approved by the Food and Drug Administration (FDA) for treating multiple sclerosis and two amyloid beta-specific humanized antibodies, Aducanumab and Lecanemab, for AD. Our previous review summarized data on recombinant antibodies evaluated in pre-clinical models for immunotherapy of neurodegenerative diseases. Here, we explore recent studies in this fascinating research field, give an update on new preventive and therapeutic applications of recombinant antibody fragments for neurological disorders and discuss the potential of antibody fragments for developing novel approaches for crossing the blood-brain barrier (BBB) and targeting cells and molecules of interest in the brain.

Cubosomes hydrogel containing silver based organometallic compounds for enhanced wound healing of burns: In vitro and in vivo studies

The aim of this study is to investigate the treatment of burn wounds and bacterial infections, specifically focusing on silver(I) N-heterocyclic carbene (Ag-NHC) loaded into cubosomes. Ag-NHC is an organometallic complex of silver (Ag) and can be considered an active pharmaceutical ingredient for the topical treatment of burns. A novel nanoparticle system, cubosome dispersions, was formulated using high pressure homogenization methods with different concentrations of lipid phase glyceryl monooleate (GMO), surfactants such as poloxamer 407 (F-127), and polyvinyl alcohol (PVA). The optimized formulation (U6) was characterized by in vitro drug release profile (90.54 ± 1.17 %), particle size (126.7 ± 0.98 nm), zeta potential (−21.6 ± 6.83 mV), entrapment efficiency (89.30 ± 1.46 %), and morphology as observed by transmission electron microscopy (TEM). The U6 formulation was incorporated into a hydrogel containing Carbopol 940 to form a cubosomal hydrogel (cubogel). The cubogel was characterized by the in vitro release of Ag-NHC (92 %), entrapment efficiency (>90 %), pH (5.3), viscosity (1.2 cP), spreadability, and TEM. From the in vitro drug release pattern, it was concluded that the U6 formulation showed slow and sustained drug release over 24 h, and demonstrated superior burn healing compared to marketed products. The in vivo wound healing study revealed that the cubogel demonstrated a superior burn healing rate compared to commercially available products (Quench® and Clotrimazole®). The in vivo histopathological results showed that the prepared cubogel was effective in treating second-degree burns, with no side effects or skin irritation, compared to commercial products. Additionally, Ag-NHC-loaded cubogel facilitated sustained release for treating burn wounds without any bacterial infections. The current findings provide a strong basis for the initiating phase 0 clinal trials, highlighting significant potential for the further research to benefit the pharmaceutical industry.

Design and optimization of stirrer and mixer design for the correct mixing of pharmaceutical powders through DEM

Mixing of granular materials is an important process for pharmaceutical industries. In this study, a quantifiable calculation method was suggested to determine the final mixing degree of the mixture. Based on that, the effect of the stirrer design, rotational speed, powder density, cohesivity, material ratios, and particle movement in the chamber guided through different designs of deflectors on the final mixing quality is examined. The results show that increasing the stirring speed, generates better mixing quality. However, introducing a varying rotational speed mode improves the mixing degree specially for binary mixtures with high relative densities. The improvement of the mixing with the number of contacting blades is observed. Finally, the introduction of a simple deflector drastically enhances the mixing quality and enables the feeding into the chamber, which is key for continuous operation with cohesive powders, making the process more stable and efficient by using more of the mixing volume.

Demystifying the ambidextrous internationalization of firms: A multiple case study in the pharmaceutical industry of an emerging economy in turbulent environment

Demystifying the ambidextrous internationalization of firms: A multiple case study in the pharmaceutical industry of an emerging economy in turbulent environment