Pharmaceutical Industry Research Articles

The Hard Way? Learning and Drug Development Success (or Failure) in the Pharmaceutical Industry

The Hard Way? Learning and Drug Development Success (or Failure) in the Pharmaceutical Industry

The Hard Way? Learning and Drug Development Success (or Failure) in the Pharmaceutical Industry

The Hard Way? Learning and Drug Development Success (or Failure) in the Pharmaceutical Industry

Changing Standards and Drug Shortages in the Pharmaceutical Industry

Changing Standards and Drug Shortages in the Pharmaceutical Industry

Recent Advances in Nanocarrier-based Approaches to Atopic Dermatitis and Emerging Trends in Drug Development and Design.

Atopic dermatitis (AD), commonly known as Eczema, is a non-communicable skin condition that tends to become chronic. The deteriorating immunological abnormalities are marked by mild to severe erythema, severe itching, and recurrent eczematous lesions. Different pharmacological approaches are used to treat AD. The problem with commercial topical preparations lies in the limitation of skin atrophy, systemic side effects, and burning sensation that decreases patient compliance. The carrier-based system promises to eliminate these shortcomings; thus, a novel approach to treating AD is required. Liposomes, microemulsions, solid lipid nanoparticles (SLNs), nanoemulsions, etc., have been developed recently to address this ailment. Despite extensive research in the development method and various techniques, it has been challenging to demonstrate the commercial feasibility of these carrier- based systems, which illustrates a gap among the different research areas. Further, different soft wares and other tools have proliferated among biochemists as part of a cooperative approach to drug discovery. It is crucial in designing, developing, and analyzing processes in the pharmaceutical industry and is widely used to reduce costs, accelerate the development of biologically innovative active ingredients, and shorten the development time. This review sheds light on the compilation of extensive efforts to combat this disease, the product development processes, commercial products along with patents in this regard, numerous options for each step of computer-aided drug design, including in silico pharmacokinetics, pharmacodynamics, and toxicity screening or predictions that are important in finding the drug-like compounds.

Effects of Withania somnifera (L.) Dunal in acute pulmonary pathophysiology in a rat model of smoke-induced lung injury and role of IRS-1 and SOX-2

The respiratory structure has a broad capacity to undergo the mechanism of regeneration. The recent study was intended to determine the efficacy of Withania somnifera (L.) Dunal and expression levels of IRS-1 and SOX-2 genes in the smoke-induced Pulmonary Injury. The present study included 3 groups (n = 9): Normal/negative control (NC), positive control/disease control (PC), and treatment group (TG; treated orally with 350 mg/kg of ethanol extract). Lung injury was induced in PC and TG groups in rats by cigarette smoke (4 CG/day). Decapitation (n = 3) was done on the 14th, 18th, and 21st day of treatment. Phenolic acid quantification by HPLC-UV/VIS showed a significant concentration of p-coumaric acid (130.2 mg/kg) that may also contribute to the extract's efficacy. Hematological parameters (leukocytes, hemoglobin, hematocrit) and serum oxidative parameters (total oxidant status and malondialdehyde) were significantly improved (P ≤ 0.05) in the TG compared to the PC group. Moreover, the total antioxidant capacity, total plasma protein, albumin, globulin, and platelet count significantly decreased in the PC while increasing in the treatment group (P ≤ 0.05). Histology showed damaged histological structures in the PC group, while there was obvious regeneration of architectural damage in the TG group. The IRS-1 and SOX-2 genes were up-regulated in the PC group, indicating the role of IRS-1 and SOX-2 gene expression in tissue homeostasis and regeneration in smoke-induced Pulmonary Injury. These results rationalize the traditional use of W. somnifera in pulmonary diseases and encourage further studies to exploit it in the pharmaceutical industry.

Changing Standards and Drug Shortages in the Pharmaceutical Industry

Changing Standards and Drug Shortages in the Pharmaceutical Industry

Oil-yielding Non-timber Plants Seeds: A Review on their Application for Health Care Products

Abstract: Oil-yielding non-timber forest products (NTFPs), such as Diploknema butyracea (Roxb.) H. J. Lam, Saipindus mukurossi Gaertn, and Hippophae salicifolia L. are widely distributed throughout Nepal and have traditionally been used as medicines by the locals since ancient times. Extensive scientific studies have demonstrated a wide range of benefits of these plants, which can have multiple uses in the pharmaceutical, cosmeceutical, and food industries. The potential of the plants, however, has not been fully explored, and they are, thus, minimally used only by locals. These plants have the potential for the development of several value-added products, leading to commercialization. This paper aims to explore in detail the health benefits and economic values of these plants to review the entrepreneurial aspects, improved farming and processing, and value addition in the product.

The Patent Landscape of mTOR and PTEN Targets.

PTEN and mTOR signaling have many roles, including antiinflammatory, immunosuppressant and cancer. US patents were retrieved to show the current landscape of the mTOR and PTEN targets. PTEN and mTOR targets were analyzed by patent analysis. The U.S. granted patents from January 2003 to July 2022 were performed and analyzed. The results showed that the mTOR target was more attractive in drug discovery than the PTEN target. Our findings indicated that most large global pharmaceutical companies focused the drug discovery related to the mTOR target. The present study demonstrated that mTOR and PTEN targets showed more applications in biological approaches compared to BRAF and KRAS targets. The chemical structures of the inhibitors of the mTOR target demonstrated some similar features to those of the inhibitors of KRAS targets. At this stage, the PTEN target may not be an ideal target subjected to new drug discovery. The present study was the first one which demonstrated that the group of O=S=O may play a critical role in the chemical structures of mTOR inhibitors. It was the first time to show that a PTEN target may be suitably subjected to new therapeutic discovery efforts related to biological applications. Our findings provide a recent insight into therapeutic development for mTOR and PTEN targets.

A Modern Curriculum for Training Scientists in Model-Informed Drug Development: Progress Report on FDA Grant to Train Regulatory Scientists.

Under US Food and Drug Administration (FDA) grant (2U18FD005320-06), the Critical Path Institute (C-Path) and experienced private sector partners collaborated with global health organizations to create didactic video materials in an e-learning format on model-informed drug development (MIDD) topics relevant to a non-modeling audience. Several multinational pharmaceutical companies contributed case studies illustrating the application of the MIDD approach in practice. Training videos were created and divided into several modules: introducing the MIDD landscape for drug development and regulatory science, a review of various model types used for MIDD, discussions of how models inform drug development and regulatory decisions, future goals of MIDD, and discussions on the interconnectedness of models used for MIDD. Examples and vignettes from stakeholders and thought leaders were included. These educational materials fill a gap between academic and "on the job training" for regulators, academic, and industry scientists, delivering insights and value for those performing modeling and non-modelers reviewing the output of modeling and simulation work. A total of 13 hours of video content is currently available. A small panel of FDA reviewers is currently beta-testing the learning management system (LMS). Future efforts for this MIDD training initiative will include expansion of the content via an expanded and diverse faculty, 1:1 online mentorship sessions, and eventually broader access to this resource consistent with an open science approach and curriculum. The MIDD training LMS can accommodate a diverse learning ecosystem; further development may also accommodate different audiences in the future.

Acute Toxicity, Anti-diabetic, and Anti-cancerous Potential of Trillium Govanianum-conjugated Silver Nanoparticles in Balb/c Mice.

The current study aimed to develop an economic plant-based therapeutic agent to improve the treatment strategies for diseases at the nano-scale because Cancer and Diabetes mellitus are major concerns in developing countries. Therefore, in vitro and in vivo antidiabetic and anti-cancerous activities of Trillium govanianum conjugated silver nanoparticles were assessed. In the current study synthesis of silver nanoparticles using Trillium govanianum and characterization were done using a scanning electron microscope, UV-visible spectrophotometer, and FTIR analysis. The in vitro and in vivo anti-diabetic and anti-cancerous potential (200 mg/kg and 400 mg/kg) were carried out. It was discovered that Balb/c mice did not show any major alterations during observation of acute oral toxicity when administered orally both TGaqu (1000 mg/kg) and TGAgNPs (1000 mg/kg), and results revealed that 1000 mg/kg is not lethal dose as did not find any abnormalities in epidermal and dermal layers when exposed to TGAgNPs. In vitro studies showed that TGAgNPs could not only inhibit alpha-glucosidase and protein kinases but were also potent against the brine shrimp. Though, a significant reduction in blood glucose levels and significant anti-cancerous effects was recorded when alloxan-treated and CCl4-induced mice were treated with TGAgNPs and TGaqu. Both in vivo and in vitro studies revealed that TGaqu and TGAgNPs are not toxic at 200 mg/kg, 400 mg/kg, and 1000 mg/kg doses and possess strong anti-diabetic and anti-cancerous effects due to the presence of phyto-constituents. Further, suggesting that green synthesized silver nanoparticles could be used in pharmaceutical industries to develop potent therapeutic agents.

A Review on Synthesis of Azoles

Abstract: Heterocyclic compounds form a major class of compounds in chemistry. There has been considerable interest in the development of novel heterocyclic compounds with varied biological activities. Azoles are famous and widespread scaffold in the pharmaceutical industry due to their range of activities. Diazocarbonyl compounds have found numerous applications in many areas of chemistry. Among the most developed fields of diazo compounds. This approach represents a useful alternative to more conventional methods of the synthesis of azoles. The present review discussed the different characteristics of the azoles of interest, to recognize the differences in pharmacolog, safety, toxicity and potential drug interactions of these antifungal agents.

Myrtus communisleaves:source of bio-actives, traditional use, their biological properties, and prospects

Myrtus communisL., commonly known as true myrtle, is a medicinal plant native to the Mediterranean area. Since ancient times, the inhabitants of this area have been using it for its cultural and medicinal properties. Because of the vast diversity of biomolecules in its aerial parts, it exhibits several biological properties, including antioxidant, antimicrobial, and anticancer properties. Thisreview retrospect the research on the source, biological activities with empirical evidence, chemical composition, applications, and cellular targets of extracts and essential oils obtained from M. communisleaves, which provides a perspective for furtherstudies on the applications and formulations of extract and EO of M. communisleaves. The efficacy of constituents' individually, in association with other bioactive constituents, or in combination with available commercial drugs would provide insights into the development of these bio-actives as future drugs and their evolving future potential applications in the pharmaceutical, food, and aroma industries.

Effects of alloferon and its analogues on reproduction and development of the Tenebrio molitor beetle

As the most numerous group of animals on Earth, insects are found in almost every ecosystem. Their useful role in the environment is priceless; however, for humans, their presence may be considered negative or even harmful. For years, people have been trying to control the number of pests by using synthetic insecticides, which eventually causes an increased level of resistance to applied compounds. The effects of synthetic insecticides have encouraged researchers to search for alternatives and thus develop safe compounds with high specificity. Using knowledge about the physiology of insects and the functionality of compounds of insect origin, a new class of bioinsecticides called peptidomimetics, which are appropriately modified insect analogues, was created. One promising compound that might be successfully modified is the thirteen amino acid peptide alloferon (HGVSGHGQHGVHG), which is obtained from the hemolymph of the blue blowfly Calliphora vicinia. Our research aimed to understand the physiological properties of alloferon and the activity of its peptidomimetics, which will provide the possibility of using alloferon or its analogues in the pharmaceutical industry, as a drug or adjuvant, or in agriculture as a bioinsecticide. We used alloferon and its three peptidomimetics, which are conjugates of the native peptide with three unsaturated fatty acids with various chain lengths: caprylic, myristic, and palmitic. We tested their effects on the morphology and activity of the reproductive system and the embryogenesis of the Tenebrio molitor beetle. We found that the tested compounds influenced the growth and maturation of ovaries and the expression level of the vitellogenin gene. The tested compounds also influenced the process of egg laying, embryogenesis, and offspring hatching, showing that alloferon might be a good peptide for the synthesis of effective bioinsecticides or biopharmaceuticals.

Genomic and Cell-Specific Regulation of Benzylisoquinoline Alkaloid Biosynthesis in Opium Poppy.

Opium poppy is a crop of great commercial value as a source of several opium alkaloids for the pharmaceutical industries including morphine, codeine, thebaine, noscapine and papaverine. Most enzymes involved in benzylisoquinoline alkaloids (BIAs) biosynthesis in opium poppy have been functionally characterized, and opium poppy currently serves as a model system to study BIA metabolism in plants. BIA biosynthesis in opium poppy involves two biosynthetic gene clusters associated respectively with the morphine and noscapine branches. Recent reports have shown that genes in the same cluster are co-expressed, suggesting they might also be co-regulated. However, the transcriptional regulation of opium poppy BIA biosynthesis is not well studied. Opium poppy BIA biosynthesis involves three cell types associated with the phloem system: companion cells, sieve elements and laticifers. The transcripts and enzymes associated with BIA biosynthesis are distributed across cell types, requiring the translocation of key enzymes and pathway intermediates between cell types. Together, these suggest that the regulation of BIA biosynthesis in opium poppy is multilayered and complex, involving biochemical, genomic, and physiological mechanisms. In this review, we highlight recent advances in genome sequencing and single cell and spatial transcriptomics with a focus on how these efforts can improve our understanding of the genomic and cell-specific regulation of BIA biosynthesis. Such knowledge is vital for opium poppy genetic improvement and metabolic engineering efforts targeting the modulation of alkaloid yield and composition.

Graph Neural Networks for Predicting Solubility in Diverse Solvents Using MolMerger Incorporating Solute-Solvent Interactions.

The prediction of solubility is a complex and challenging physicochemical problem that has tremendous implications for the chemical and pharmaceutical industry. Recent advancements in machine learning methods have provided a great scope for predicting the reliable solubility of a large number of molecular systems. However, most of these methods rely on using physical properties obtained from experiments and expensive quantum chemical calculations. Here, we developed a method that utilizes a graphical representation of solute-solvent interactions using "MolMerger," which captures the strongest polar interactions between molecules using Gasteiger charges and creates a graph incorporating the true nature of the system. Using these graphs as input, a neural network learns the correlation between the structural properties of a molecule in the form of node embedding and its physicochemical properties as the output. This approach has been used to calculate molecular solubility by predicting the Log solubility values of various organic molecules and pharmaceuticals in diverse sets of solvents.

Determination of prebiotic activity and probiotic encapsulation ability of inulin type fructans obtained from Inula helenium roots.

Inulin, a prebiotic utilized in the food and pharmaceutical industries, promotes the growth of beneficial bacteria in the colon, thereby enhancing human health. Although inulin is commercially produced from chicory and artichoke, Inula helenium roots offer a high potential for inulin production. The aim of this study is to investigate the prebiotic activity of inulin (inulin-P) from I. helenium roots on Lactobacillus rhamnosus, as well as its ability to produce synbiotic microcapsules and the effects on probiotic viability during freeze-drying, in vitro gastrointestinal (GI) digestion, and storage. First, the effect of inulin-P on L. rhamnosus viability and short-chain fatty acid (SCFA) production was compared to other commonly utilized prebiotics. The findings revealed that inulin-P remarkably promoted the growth and SCFA yield of L. rhamnosus for 48h of fermentation and 28 days of storage. Then, L. rhamnosus was encapsulated with inulin-P and commercial inulin to compare its survival throughout storage and the GI tract. Inulin-P microcapsules outperformed in terms of viability during storage (7.98logCFU/g after 30 days at 4°C). Furthermore, inulin-P microcapsules were heat-resistant and protected L. rhamnosus from GI conditions, resulting in a high survival rate (89.52%) following large intestine simulation, which is ideal for increasing customer benefits. Additionally, inulin-P microcapsules exhibited similar physical characteristics to commercial inulin. Consequently, this study revealed that inulin-P, which is easy to produce, low-cost, and has industrial application potential, could be used as a good carrier for the synbiotic encapsulation of L. rhamnosus. PRACTICAL APPLICATION: Inulin is a prebiotic that promotes the activity and growth of beneficial bacteria in the human gut. Although commercial inulin is currently produced from chicory root and artichoke, Inula helenium root is a potential raw material for inulin production. In this study, inulin was produced from I. helenium roots with a low-cost and easy production method, and it was determined that this inulin was an effective carrier in the synbiotic encapsulation of L. rhamnosus. This inulin exhibits superior prebiotic activity and encapsulation efficiency compared to commercial inulins like Orafti® GR and HPX and can be easily integrated into industrial production.

Expression of the changes in essential oil components of Shirazi thyme (Zataria multiflora Boiss.) as affected by various drying methods

The purpose of this research was to investigate the impact of various drying techniques on the quality characteristics of Shirazi thyme (Zataria multiflora Boiss.) using a completely randomized design with three replications. The treatments included fresh samples, shade-drying (SHD), sun-drying (SD), oven and vacuum-drying (OD and VD) each at three different temperatures (45, 55, and 65 °C), and microwave-drying (MD) at three different power levels (200, 400, and 600 W). The results indicated that vacuum and oven-drying at 45 °C were effective in preserving valuable secondary metabolites compared to traditional drying methods. The essential oil (EO) content was lowest in the microwave-drying at 600 W (1.3 %), and highest in vacuum-drying at 45 °C (2.99 %). Vacuum-drying at 45 °C also produced the highest levels of carvacrol (72.5 %) and thymol (7.21 %) content, while the lowest levels were found in fresh samples. The main components in the EO were monoterpene hydrocarbons (11.47–27.33 %), oxygenated monoterpenes (74.81–86.9 %), and oxygenated sesquiterpenes (76.50–86.50 %). The results showed that the amount of sesquiterpene hydrocarbons and oxygenated monoterpenes were higher at low temperatures. Furthermore, the color parameters showed changes based on the drying methods, with vacuum-drying at 45 °C increasing the L* parameter (lightness), vacuum-drying at 65 °C increasing the a* parameter)brightness(, and oven-drying at 45 °C increasing the b* parameter)greenness). Understanding the different methods and operations of drying Shirazi thyme can provide valuable insight for its professional application and development in food and pharmaceutical industries.

Production of 5-fluorouracil-loaded PLGA nanoparticles with toroidal microfluidic system and optimization of process variables by design of experiments

In recent decades, microfluidics has presented new opportunities for the production of nanoparticles (NPs). However, to achieve rapid clinical translation, the production of PLGA NPs in a single microfluidic channel for both the pharmaceutical research and industry without the need for scaling is still limited. The aim of this study was to accomplish the production of reproducible and stable 5-FU loaded Poly(lactic-co-glycolic acid) (PLGA) NPs, using an innovative toroidal microfluidic system, for cancer therapy. The toroidal microfluidic system enabled the production of spherical NPs ranging from 100 to 150 nm by adjusting both the TFR within the range of 5–15 mL/min and FRR between 1:3 to 1:7. A systematic assessment of critical process variables (total flow rate; TFR, flow rate ratio; FRR) for the production of PLGA NPs was conducted using Design of Experiment (DoE). The NPs, which exhibit a uniform size distribution, remained stable even after centrifugation and storage for 3 months at 4 °C. The encapsulation efficiency of drug and the concentration of NPs were not affected by changing process parameters. The effective 5-FU encapsulation into NPs resulted in a controlled in vitro drug release. Due to the controlled release profile of the 5-FU loaded PLGA NPs, the formulation was a promising candidate for mitigating the toxic side effects of free 5FU and improving cancer treatment. In conclusion, toroidal microfluidic system enables high-volume production of stable PLGA NPs, both with and without 5-FU.

Unveiling the mucilage complexity in a multispecies exploration of the genus Alcea from Iran

Eight field-grown Alcea species (A. koelzii, A. kurdica, A. lavateriflora, A. rechingeri, A. remotiflora, A. rufescenc, A. schiraziana and A. tehranica) were analyzed for their mucilage content to identify the species with the highest yield. The mucilage was extracted with boiling water, precipitated by methanol, and subjected to acid hydrolysis by trifluoroacetic acid. Although mucilage content varied across Alcea species, root yields generally exceeded flower yields, with A. rechingeri roots reaching up to 26.43 %. HPLC analysis showed glucose as the dominant monosaccharide in root mucilage across all species. Rhamnose and fructose content, however, exhibited variations among the species. Field emission scanning electron microscopy micrographs showed layered or fibrous structures, while Fourier Transform Infrared Spectroscopy analysis confirmed a polysaccharide-based composition for flower and root mucilage. Energy dispersive X-ray analysis detected calcium, phosphorus, and magnesium, with higher concentrations in flower mucilage. X-Ray diffraction analysis confirmed the presence of both amorphous and semi-crystalline regions within the mucilage samples, with crystalline phases identified as calcium oxalate hydrate, alpha-cyclodextrin, and glutamic acid. In conclusion, A. koelzii flowers and A. rechingeri roots yielded the highest mucilage content, suggesting Alcea as a promising source of polysaccharides with potential applications in the pharmaceutical and food industries.

Deciphering the role and impact of India's pharmaceutical industries and its regulatory compliance

The pharmaceutical industry faces exceptionally high R&D costs, with the US research-based sector investing about 17% of sales into R&D. The cost of bringing a new compound to market was estimated at $802 million in 2001, up from $138 million in the 1970s and $318 million in the 1990s, necessitating stringent regulations. This study aims to determine the role and impact of India's pharmaceutical industry and its regulatory compliance. Personnel from organizations established between 1884 and 2004, with turnovers ranging from Rs. 25 crore (US $5.3 million) to Rs. 5500 crore (US $1.2 billion), were surveyed. Out of 150 companies approached, 73 responded, with 70 complete responses analyzed. Ongoing interactions with regulatory agencies helped companies better understand the regulatory system. Three key areas emerged as priorities: awareness of intellectual property rights (IPR) and patents, fostering a suitable environment for research and development, and implementing Good Manufacturing Practices (GMP), considered more critical than price control. The findings underscore the importance of regulatory compliance in promoting innovation and maintaining quality within the pharmaceutical industry, ensuring its competitiveness and ability to meet global standards.