Development Of Pharmaceutical Products Research Articles

A Guide to Best Practice in Sensory Analysis of Pharmaceutical Formulations.

It is well established that treatment regime compliance is linked to the acceptability of a pharmaceutical formulation, and hence also to therapeutic outcomes. To that end, acceptability must be assessed during the development of all pharmaceutical products and especially for those intended for paediatric patients. Although acceptability is a multifaceted concept, poor sensory characteristics often contribute to poor patient acceptability. In particular, poor taste is often cited as a major reason for many patients, especially children, to refuse to take their medicine. It is thus important to understand and, as far as possible, optimise the sensory characteristics and, in particular, the taste/flavour/mouthfeel of the formulation throughout the development of the product. Sensory analysis has been widely practiced, providing objective data concerning the sensory aspects of food and cosmetic products. In this paper, we present proposals concerning how the well-established principles of sensory analysis can best be applied to pharmaceutical product development, allowing objective, scientifically valid, sensory data to be obtained safely. We briefly discuss methodologies that may be helpful in reducing the number of samples that may need to be assessed by human volunteers. However, it is only possible to be sure whether or not the sensory characteristics of a pharmaceutical product are non-aversive to potential users by undertaking sensory assessments in human volunteers. Testing is also required during formulation assessment and to ensure that the sensory characteristics remain acceptable throughout the product shelf life. We provide a risk assessment procedure to aid developers to define where studies are low risk, the results of a survey of European regulators on their views concerning such studies, and detailed guidance concerning the types of sensory studies that can be undertaken at each phase of product development, along with guidance about the practicalities of performing such sensory studies. We hope that this guidance will also lead to the development of internationally agreed standards between industry and regulators concerning how these aspects should be measured and assessed throughout the development process and when writing and evaluating regulatory submissions. Finally, we hope that the guidance herein will help formulators as they seek to develop better medicines for all patients and, in particular, paediatric patients.

Organoid-on-a-chip: Current challenges, trends, and future scope toward medicine.

In vitro organoid models, typically defined as 3D multicellular aggregates, have been extensively used as a promising tool in drug screening, disease progression research, and precision medicine. Combined with advanced microfluidics technique, organoid-on-a-chip can flexibly replicate in vivo organs within the biomimetic physiological microenvironment by accurately regulating different parameters, such as fluid conditions and concentration gradients of biochemical factors. Since engineered organ reconstruction has opened a new paradigm in biomedicine, innovative approaches are increasingly required in micro-nano fabrication, tissue construction, and development of pharmaceutical products. In this Perspective review, the advantages and characteristics of organoid-on-a-chip are first introduced. Challenges in current organoid culture, extracellular matrix building, and device manufacturing techniques are subsequently demonstrated, followed by potential alternative approaches, respectively. The future directions and emerging application scenarios of organoid-on-a-chip are finally prospected to further satisfy the clinical demands.

Determination of Heavy Metal Content: Arsenic, Cadmium, Mercury, and Lead in Cyano-Phycocyanin Isolated from the Cyanobacterial Biomass.

Cyano-phycocyanin (C-PC) is a light-absorbing biliprotein found in cyanobacteria, commonly known as blue-green algae. Due to its antioxidative, anti-inflammatory, and anticancer properties, this protein is a promising substance in medicine and pharmaceuticals. However, cyanobacteria tend to bind heavy metals from the environment, making it necessary to ensure the safety of C-PC for the development of pharmaceutical products, with C-PC isolated from naturally collected cyanobacterial biomass. This study aimed to determine the content of the most toxic heavy metals, arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in C-PC isolated from different cyanobacterial biomasses collected in the Kaunas Lagoon during 2019-2022, and compare them with the content of heavy metals in C-PC isolated from cultivated Spirulina platensis (S. platensis). Cyanobacteria of Aphanizomenon flos-aquae (A. flos-aquae) dominated the biomass collected in 2019, while the genus Microcystis dominated the biomasses collected in the years 2020 and 2022. Heavy metals were determined using inductively coupled plasma mass spectrometry (ICP-MS). ICP-MS analysis revealed higher levels of the most investigated heavy metals (Pb, Cd, and As) in C-PC isolated from the biomass with the dominant Microcystis spp. compared to C-PC isolated from the biomass with the predominant A. flos-aquae. Meanwhile, C-PC isolated from cultivated S. platensis exhibited lower concentrations of As and Pb than C-PC isolated from naturally collected cyanobacterial biomass.

Intriguing of pharmaceutical product development processes with the help of artificial intelligence and deep/machine learning or artificial neural network

Intriguing of pharmaceutical product development processes with the help of artificial intelligence and deep/machine learning or artificial neural network

Sulfated Polysaccharides from Seaweeds: A Promising Strategy for Combatting Viral Diseases-A Review.

The limited availability of treatments for many infectious diseases highlights the need for new treatments, particularly for viral infections. Natural compounds from seaweed are attracting increasing attention for the treatment of various viral diseases, and thousands of novel compounds have been isolated for the development of pharmaceutical products. Seaweed is a rich source of natural bioactive compounds, including polysaccharides. The discovery of algal polysaccharides with antiviral activity has significantly increased in the past few decades. Furthermore, unique polysaccharides isolated from seaweeds, such as carrageenan, alginates, fucoidans, galactans, laminarians, and ulvans, have been shown to act against viral infections. The antiviral mechanisms of these agents are based on their inhibition of DNA or RNA synthesis, viral entry, and viral replication. In this article, we review and provide an inclusive description of the antiviral activities of algal polysaccharides. Additionally, we discuss the challenges and opportunities for developing polysaccharide-based antiviral therapies, including issues related to drug delivery and formulation. Finally, this review highlights the need for further research for fully understanding the potential of seaweed polysaccharides as a source of antiviral agents and for developing effective treatments for viral diseases.

Enhancing Antioxidant Properties of Prunus spinosa Fruit Extracts via Extraction Optimization

Prunus spinosa fruit, commonly known as blackthorn or sloe, possesses a wide range of health-promoting properties, including antioxidant and antibacterial activities. In this study, we investigated the effects of various extraction parameters, such as temperature, time, and solvent composition, on the extraction of bioactive compounds from P. spinosa fruit. Response surface methodology was employed to optimize these parameters and evaluate their impact on the antioxidant properties of the extracts. Furthermore, techniques such as ultrasound (US) and pulsed electric field (PEF) were applied, both individually and in combination, to explore their potential effects on the extraction process. The optimal extraction technique proved to be the combination of PEF and US, followed by stirring. The most suitable solvent was 75% ethanol, whereas the optimum extraction time and temperature were 30 min and 80 °C, respectively. Our findings revealed that under the optimum extraction parameters, a significant improvement in the extraction efficiency of bioactive compounds from P. spinosa fruit was achieved. More specifically, the optimal conditions, according to partial least squares (PLS) analysis, were a combination of all three extraction modes (PEF‒US‒ST), the shorter extraction time of the present study (30 min), and the corresponding higher temperature (80 °C). As expected, the presence of ethanol was considered necessary, even in an amount of 25%. The total polyphenol content was found to be 30.74 mg gallic acid equivalent (GAE)/g, the total flavonoids content 3.23 mg rutin equivalents (RtE)/g and the total anthocyanins 125.2 μg cyanidin-3-O-glucoside equivalents (CyE)/g. HPLC-DAD analysis showed that neochlorogenic acid was the polyphenol with the highest concentration (4.13 mg GAE/g) in P. spinosa fruit. The antioxidant activity of the optimized, according to PLS analysis, extract was evaluated and found to be 146.09 μmol ascorbic acid equivalent (AAE)/g determined by ferric reducing antioxidant power (FRAP) assay, and by the radical scavenging activity (DPPH) assay was 18.56 μmol AAE/g. Additionally, the ascorbic acid was determined to be 119.4 mg/100 g. Overall, this study contributes valuable insights into the extraction optimization process and the potential applications of P. spinosa fruit in the development of functional foods and pharmaceutical products.

Biological Characterization and Metabolic Variations among Cell-Free Supernatants Produced by Selected Plant-Based Lactic Acid Bacteria.

The aim of this research was to assess the antibacterial and antioxidant properties as well as the variation in metabolites of the cell-free supernatant (CFS) produced by lactic acid bacteria (LAB) from local plants: Lactiplantibacillus plantarum ngue16, L. plantarum ng10, Enterococcus durans w3, and Levilactobacillus brevis w6. The tested strains exhibited inhibitory effects against pathogens, including Bacillus cereus, B. subtilis, Cronobacter sakazakii, Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus using the agar spot assay and well diffusion method. The CFS from all four strains displayed antibacterial activity against these pathogens with minimum inhibitory concentration (MIC) values ranging from 3.12 to 12.5 mg/mL and minimal bactericidal concentration (MBC) values ranging from 6.25 to 25.0 mg/mL. Moreover, the CFS demonstrated resilience within specific pH (3-8) and temperature (60-100 °C) ranges and lost its activity when treated with enzymes, such as Proteinase K and pepsin. Furthermore, the CFS exhibited antioxidant properties as evidenced by their ability to inhibit the formation of two radicals (1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) compared to the negative control, De Man, Rogosa, and Sharpe (MRS) broth. The use of proton-based nuclear magnetic resonance (1H-NMR) spectroscopy revealed the presence and quantification of 48 metabolites in both the CFS and MRS broths. Principal Component Analysis (PCA) effectively differentiated between CFS and MRS broth by identifying the specific metabolites responsible for the observed differences. The partial least squares (PLS) model demonstrated a significant correlation between the metabolites in the LAB supernatant and the tested antibacterial and antioxidant activities. Notably, anserine, GABA, acetic acid, lactic acid, uracil, uridine, propylene glycol, isopropanol, serine, histidine, and indol-3-lactate were identified as the compounds contributing the most to the highest antibacterial and antioxidant activities in the supernatant. These findings suggest that the LAB strains investigated have the potential to be utilized in the production of functional foods and the development of pharmaceutical products.

Biological Importance of Flavonoid Bavachinin in the Medicine: Perspectives of Medicinal Importance, Pharmacological Activities and Analytical Techniques

Backgrounds: Phytochemicals are an important class of natural compounds present in vegetables, herbs, fruits, and seeds. Phytochemicals have been used in medicine for the treatment of human disorders in the form of drugs, medicine, and Nutraceuticals. Flavonoid class secondary metabolites were found to be present in medicinal plants and some food materials derived from plants. Flavonoid class phytochemicals have beneficial health aspects and numerous pharmacological activities in the medicine. Psoralea corylifolia has been widely used in medicine for the treatment of skin diseases, including vitiligo, alopecia areata, leukoderma, and psoriasis. More than 90 different types of phytocompounds have been separated and isolated from Psoralea corylifolia. Bavachinin is a flavonoid class phytochemical, found to be present in the seeds of Psoralea corylifolia. Bavachinin possesses anti-bacterial, anti-oxidative, anti-inflammatory, α-glucosidase and nitric oxide inhibitory potential. Method: Scientific data on bavachinin have been collected from different literature databases such as Google, Google Scholar, PubMed, Science Direct and Scopus in the present work and analyzed to know the biological importance of bavachinin. Scientific research data on bavachinin have been collected in the present work for their medicinal importance, pharmacological activities and analytical aspects. Further, all the collected scientific data have been separated into different sub-sections i.e., Medicinal importance, pharmacological activities and analytical aspects of bavachinin. Detailed pharmacological activity data of bavachinin have been analyzed in the present work to know the therapeutic potential of bavachinin in medicine. Analytical data of bavachinin have been collected and analyzed in the present work to know the biological importance of bavachinin in modern medicine for the standardization of Psoralea corylifolia. Results: Literature data analysis of different scientific research works revealed the biological importance of flavonoids in medicine. Flavonoid class phytochemicals have anti-inflammatory, antioxidant, anti-viral, anti-cancer and anti-ageing properties in medicine. Scientific data analysis revealed the effectiveness of bavachinin in cancer, blood glucose, Alzheimer's disease, Parkinson's disease, inflammation, immune system, T cell differentiation, oxidative damage and enzymes. However, therapeutic efficacy, metabolism, biotransformation, pharmaceutical product development and pharmacokinetic parameters of bavachinin have also been discussed in the present work. Analytical data signified the importance of modern analytical tools for the separation, isolation and identification of bavachinin. Conclusion: Scientific data analysis of different research work revealed the biological importance and therapeutic benefit of bavachinin in medicine.

Avaliação das atividades antibacteriana e antioxidante do óleo essencial do araçá-roxo (Psidium rufum, Myrtaceae)

ABSTRACT The aim of this study was to evaluate the antibacterial and antioxidant activities of essential oil (EO) from fresh leaves of Psidium rufum. The EO was extracted by hydrodistillation and identified by gas chromatography coupled to mass spectrometry. The antibacterial activity was evaluated by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Antioxidant activity was determined by β-carotene/linoleic acid co-oxidation system, 2,2-diphenyl-1-picrylhydrazyl radical scavenging and iron reduction methods. Hydrocarbon sesquiterpenes were the predominant class, indicating 1,8 cineole, α-longipinene as major. The EO was tested against the bacteria Staphylococcus aureus and Pseudomonas aeruginosa (MIC = 2,500 µg/mL and MBC = 20,000 µg/mL); Enterococcus faecalis (MIC = 2,500µg/mL and MBC > 20,000µg/mL) and Escherichia coli (MIC > 20,000µg/mL and MBC > 20,000µg/mL). The EO showed antioxidant potential due to β-carotene/linoleic acid co-oxidation system, with 76.63% of oxidation inhibition (1.0mg/mL) and due to the iron reduction power (5,38 μmol Fe 2+ /mg sample). The results are promising in recommending this species for the development of food, cosmetic and pharmaceutical products.

Assessment of the effect of the extract Arthrospira platensis on human skin microbiota

A new direction in the development of pharmaceutical and cosmetic products, provides for the widespread use of pigment containing components of extracts of microalgae and blue-green algae. However, the use of these components requires a deeper study of their effect on humans, including on their microbiota. In our experiments, it was found that the extract of the blue-green algae Arthrospira platensis (commercial name of the drug Spirulina), with a phycocyanin content of 38%, is able to influence the overall microbiota of human skin, and to varying degrees of effectiveness depending on the concentration of the drug. It is shown that the effect of the studied extract has a dose-dependent effect, both when affecting the general microbiota of human skin and on representatives of its gram-positive microbiota. The gram-negative microbiota of human skin is less sensitive to the action of the extract of the blue-green algae Arthrospira platensis (commercial name of the drug Spirulina), since only at a concentration of 200 mcg/ml there was a significant low increase in biomass.

Current status and vision of local pharmaceutical industries in Saudi Arabia: The focus on nanomedicines

BackgroundPharmaceutical nanomedicine products are expected to impact the global pharmaceutical market and healthcare system significantly. Since 2000, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved over 80 nanomedicine products for marketing; an additional double that number is currently being tested in clinical trials. The nanomedicine market is expected to reach USD 350.8 billion by 2025 from USD 138.8 billion in 2016. This demonstrates the importance of nanotechnology to the delivery of pharmaceuticals. The main benefits of employing nanotechnology to distribute therapeutic agents include reducing the undesired toxicity from non-specific distribution and increasing patient adherence, which can indirectly minimize the burden on the country's healthcare system. Such products are expected to gain a significant economic impact on Saudi Arabia’s pharmaceutical drugs market once they get developed locally. MethodA descriptive and cross-sectional study, including a web-based questionnaire and a complete categorization of pharmaceutical products formed by the national industries in Saudi Arabia, was utilized to investigate the current and future direction of pharmaceutical manufacturing exploiting nanotechnology in the Kingdom. ResultsThe survey showed an apparent lack of willingness within the national pharmaceutical industries, as the majority (≈ 86%) of the leading Saudi companies cannot enable nanotechnology-based medicines in their manufacturing. However, more than 93% of the national pharmaceutical industries, upon the basis of the responses, agreed that the development of pharmaceutical products with nanotechnology is an important step toward solving various complications associated with conventional forms of the available medicine. ConclusionNational pharmaceutical industries in Saudi Arabia will need to get closer to manufacturing nanomedicines by partnering with international pioneer companies. In addition, empowering the local research and development (R&D) centers in nano delivery systems could facilitate translating their R&D outcomes into novel advanced and commercialized products. This could imitate the direction of the global pharmaceutical market and share its revenue which will positively reflect on the Kingdom's economy.

Structural Design of Oleogel‐Hydrogel Bigels for Co‐Delivery of Curcumin and Epigallocatechin Gallate with Synergistic Stability and Bioactivity

AbstractBigels are novel biphasic systems containing hydrogel and oleogel structures, which are designed to deliver multiple bioactives for synergistic activity. The current study develops bigels based on a carrageenan hydrogel and a monoglyceride (GMS) oleogel. Results show that the microstructures of bigels are facilely modified by two surface active ingredients (Tween 20 and polyglycerol polyricinoleate), which then influence the microstructures of the bigels. When curcumin and epigallocatechin gallate (EGCG) are delivered simultaneously, the bioactives work synergistically to slow thermal degradation. Simulated digestion tests indicate that the bigel structures can delay the release of the two bioactives in artificial saliva and simulated gastric fluid (SGF), and allow fast release in simulated intestinal fluid (SIF). DPPH and ABTS tests show the digested Tween 20 bigels containing EGCG and curcumin present synergistic antioxidant activity. Anticancer activity is evaluated in human colon adenocarcinoma HCT116, and the two bioactives work cooperatively to lower cell viability. The bioactives released from Tween 20 bigels have higher cytotoxicity than those from polyglycerol polyricinoleate bigels. The results reveal that facile structural design of bigels has the potential to achieve synergistic stability and bioactivity of co‐delivered bioactives, which is meaningful for the development of functional pharmaceutical, cosmetic, and food products.

Phytochemical screening, phenolic and flavonoid content, and antioxidant activity of Rhizophoraceae methanol extracts from Langsa, Aceh, Indonesia

Abstract. Indriaty, Djufri, Ginting B, Hasballah K. 2023. Phytochemical screening, phenolic and flavonoid content, and antioxidant activity of Rhizophoraceae methanol extracts from Langsa, Aceh, Indonesia. Biodiversitas 24: 2865-2876. Bruguiera cylindrica (L.) Blume,Bruguiera gymnorrhiza (L.) Lam., Ceriops decandra (Griff.) Ding Hou, Rhizophora apiculate Blume, and Rhizophora mucronata Lam. are mangrove plant species belonging to Rhizophoraceae that have been used as medicinal plants. Studies on phytochemical screening and bioactivity of Rhizophoraceae mangrove plants from the Aceh region are still limited. This study aimed to analyze the chemical compounds in Rhizophoraceae from Aceh and determine total phenolic content (TPC), flavonoid content (TFC), and antioxidant activity. The chemical compounds were determined using qualitative assay, TLC, and Gas Chromatography-Mass Spectrophotometry (GC-MS). The antioxidant activity was tested against 2,2-diphenyl-1-picrylhydrazyl (DPPH). Twenty extracts from various plant parts of Rhizophoraceae (roots, bark, leaves, and fruit/hypocotyl) were used in this study. The phytochemical screening of Rhizophoraceae plants revealed the presence of alkaloids, flavonoids, phenolics (tannins), terpenoids, steroids, and saponins. The highest TPC content was obtained from the bark of R. mucronata (484.39 mg GAE/g extract). Furthermore, the highest TFC was found in the leaves of R. apiculata ( 15.23 mg QE/g extract). Nineteen extracts had very high antioxidant activity (IC50: 2.35 ± 0.01 - 29.84 ± 0.19 µg/mL). The bark and roots of C. decandra had the most potent antioxidant activity (IC50: 2.35 0.01 and 3.23 0.01 µg/mL, respectively). The GC-MS revealed the presence of pyrocatechol (15.85%), antiarol (1.44%), and hexadecanoic acid (1.69%), that act as antioxidants. Therefore, it can be concluded that the Rhizophoraceae methanol extract contains phenols in the stem bark and flavonoids in the leaves with very high antioxidant activity as a good source of natural ingredients for future pharmaceutical product development. It is highly recommended to do further research to obtain pure compounds from these plants.

Brucella abortus antigen omp25 vaccines: Development and targeting based on Lactococcus lactis.

Most Brucella infections take place on mucosal membranes. Therefore, creating vaccinations delivered through the mucosa may be crucial for managing brucellosis. Consequently, we assessed the efficacy of a recombinant oral antigen delivery system based on Lactococcus lactis for Brucella abortus omp25 antigen. Oral vaccinations with L. lactis transformed with pNZ8148 variants encoding for omp25 (pNZ8148:omp25) and free-pNZ8148 were administered to mice. On day 30, following immunization in animal groups, anti-omp25-specific IgG1 antibodies were assessed by the ELISA test. Additionally, nasal and bronchoalveolar lavages containing omp25-specific secretory IgA (sIgA) were analysed by ELISA. ELISA test and real-time PCR were also used to analyse cytokine responses up to 28 days following the last boost. In addition, the protective potential of L. lactis pNZ8148:omp25 vaccines was assessed in BALB/c mice by exposing them to the B. abortus strain. Based on the initial screening results, the omp25 protein was identified for immunogenicity because it had the maximum solubility and flexibility and antigenic values of 0.75. The produced plasmid was digested using KpnI and XbaI. By electrophoretic isolation of the digestion fragments at 786bp, the omp25 gene, the successful production of the recombinant plasmid, was confirmed. Antigen expression at the protein level revealed that the target group generated the 25kDa-sized omp25 protein, but there was no protein expression in the control group. Fourteen days after priming, there was a considerable amount of omp25-specific IgG1 in the sera of mice vaccinated with pNZ8148-Usp45-omp25-L. lactis (p<0.001 in target groups compared to the phosphate-buffered saline control group). IFN-γ and TNF-α levels were more significant in samples from mice that had been given the pNZ8148-Usp45-omp25-L. lactis and IRBA vaccinations, in samples taken on days 14 and 28, respectively (p<0.001). The pNZ8148-Usp45-omp25-L. lactis and IRBA immunization groups had significantly greater IL-4 and IL-10 transcription levels than the other groups. The spleen portions from the pNZ8148-Usp45-omp25-L. lactis and IRIBA vac group had less extensive spleen injuries, alveolar oedema, lymphocyte infiltration and morphological damage due to the inflammatory process. Our study offers a novel method for using the food-grade, non-pathogenic and noncommercial bacterium L. lactis as a protein cell factory to produce the novel immunogenic fusion candidate romp25. This method offers an appealing new approach to assessing the cost-effective, safe, sustainable, simple pilot development of pharmaceutical products.

Banana Peel: A potential waste product with numerous pharmacological activities

Plants have been used as a traditional medicine for generations. Recently the pharmaceutical industries are showing a great interest in using plant extracts in pharmaceutical product development due to the uses of the plants in the treatment of various diseases. Banana is a world-wide edible fruit which comes from south-east Asia. It belongs to the genus Musa and is of two types, sweet banana, and plantain. It has many different species in the world, which are divided into 50 groups. The scientific names of cultivated bananas are Musa accuminata, Musa balbisiana and Musa paradisiaca belonging to the family Musaceae. The present review discusses the various pharmacological activities of the banana peel.

Efficient production of recombinant proteins in suspension CHO cells culture using the Tol2 transposon system coupled with cycloheximide resistance selection

DNA recombination techniques in mammalian cells has been applied to the production of therapeutic proteins for several decades. To be used for commercial production, established cell lines should stably express target proteins with high productivity and acceptable quality for human use. In the conventional transfection method, the screening process is laborious and time-consuming since superior cell lines had to be selected from an enormous number of transfected cell pools and clonal cell lines with a wide variety of transgene insertion locations. In this study, we demonstrated that the combination of a Tol2 transposon system and cell selection by cycloheximide resistance is an efficient method to express therapeutic proteins, such as human antibody in suspension culture of Chinese hamster ovary cells. The resulting stable cell lines showed constant productivity and cell growth over a long enough cultivation periods for recombinant protein production. We anticipate that this approach will prove widely applicable to protein production in research and development of pharmaceutical products.

Algorithm for the early prediction of drug stability using bayesian inference and multiple measurements: Application for predicting the stability of silodosin tablets

The stability of active pharmaceutical ingredients (APIs) and formulations has become a major chemistry, manufacturing, and control (CMC) concern in the pharmaceutical industry because it can determine the feasibility of research and development, the development period, and the development costs of a certain formulation. To streamline the research and development of pharmaceutical products and create useful pharmaceutical products at an early stage, a technology that predicts the stability of formulations at an early stage and with a high degree of accuracy is needed. When predicting the stability of a substance, highly reliable data are required; however, the stability data are affected by analytical variations that depend on the experimenter, measurement device, and conditions used. Although these variations greatly affect the prediction accuracy, a stability prediction method that considers these variations has not yet been developed. Here, short-term stability data under accelerated conditions were obtained at three institutions using silodosin tablets as a model sample. By combining Bayesian inference with the temporal change in the amount of the main degradation products obtained and the conventional humidity-corrected Arrhenius equation, we developed a new algorithm that provides a narrow confidence interval, even when using data with variations. By using this algorithm and setting an appropriate number of conditions, we were able to obtain a valid confidence intervals in a short period of time. Here, by performing more measurements than those suggested by the minimum measurement frequency indicated in the guideline specified in the International Council for Harmonisation (ICH) of Technical Requirements for Pharmaceuticals for Human Use, we developed a method that can be used to reasonably predict the long-term stability of the drugs, even if the data measurement interval is short. Our results will help solve various problems in today's pharmaceutical product development scenario and contribute to worldwide health and welfare.

Usefulness of the Beagle Model in the Evaluation of Paracetamol and Ibuprofen Exposure after Oral Administration to Pediatric Populations: An Exploratory Study.

The present study aimed to explore the usefulness of beagle dogs in combination with physiologically based pharmacokinetic (PBPK) modeling in the evaluation of drug exposure after oral administration to pediatric populations at an early stage of pharmaceutical product development. An exploratory, single-dose, crossover bioavailability study in six beagles was performed. A paracetamol suspension and an ibuprofen suspension were coadministered in the fasted-state conditions, under reference-meal fed-state conditions, and under infant-formula fed-state conditions. PBPK models developed with GastroPlus v9.7 were used to inform the extrapolation of beagle data to human infants and children. Beagle-based simulation outcomes were compared with published human-adult-based simulations. For paracetamol, fasted-state conditions and reference-meal fed-state conditions in beagles appeared to provide adequate information for the applied scaling approach. Fasted-state and/or reference-meal fed-state conditions in beagles appeared suitable to simulate the performance of ibuprofen suspension in pediatric populations. Contrary to human-adult-based translations, extrapolations based on beagle data collected under infant-formula fed-state conditions appeared less useful for informing simulations of plasma levels in pediatric populations. Beagle data collected under fasted and/or reference-meal fed-state conditions appeared to be useful in the investigation of pediatric product performance of the two investigated highly permeable and highly soluble drugs in the upper small intestine. The suitability of the beagle as a preclinical model to understand pediatric drug product performance under different dosing conditions deserves further evaluation with a broader spectrum of drugs and drug products and comparisons with pediatric in vivo data.

Eco-Friendly Extraction of Green Coffee Oil for Industrial Applications: Its Antioxidant, Cytotoxic, Clonogenic, and Wound Healing Properties

The development of natural oil-based cosmetic and pharmaceutical products presents great scientific and commercial interest. Herein, we aimed to extract green coffee oil from Arabic coffee by a sustainable cold-pressing method. Furthermore, this work aimed to characterize the obtained green coffee oil by Fourier-Transform Infrared (FT–IR) and ultraviolet–visible spectroscopies (UV–Vis), peroxide analysis, and fatty acids profile by gas chromatography–mass spectrometry (GC–MS). Moreover, the functional and biological properties of the obtained green coffee oil and a green-coffee oil-based commercial product (Energy up®, Dermociencia) were investigated. The green coffee oil presented linoleic and palmitic acids as the major fatty acids showing 44.8% and 35.4%, respectively. Moreover, this green coffee oil presented an antioxidant activity (EC50 7.64 mg/mL) and an absence of cytotoxic effects in keratinocyte cultures treated with up to 20 mg/mL. The obtained green coffee oil showed wound healing properties as well as clonogenic efficiency, a biological potential to induce the proliferative and migratory capacity of cells of human skin keratinocytes at 2.5 mg/mL. The samples presented high antioxidant activity and the absence of a cytotoxic effect, suggesting that green coffee oil is a promising natural product for cosmetic applications with wound healing properties. These results open new ways for the use of green coffee oil for the development of cosmetic and pharmaceutics natural-based products.

An Overview on Quality by Design

Quality by Design (QbD) has as a new concept for the development of high-quality pharmaceutical products. It is an essential component of the modern approach to pharmaceutical quality. QbD is the best way to build quality into all pharmaceutical products, but it poses a significant challenge to the pharmaceutical industry, whose processes are time-bound, despite inherent process and material variability. Throughout the design and development of a product, it is critical to define the desired product performance profile [Target Product Profile (TPP), Target Product Quality Profile (TPQP)] and identify critical quality attributed to the product (CQA). Applications of QbD to pharmaceutical processes (formulation development) and analytical development are briefly discussed. A standardized pharmaceutical quality system that is applicable throughout the product's lifecycle and emphasizes an integrated approach to risk management and science should be developed, resulting in better quality medicines for patients.ICH documents such as ICH Q8, i.e. Pharmaceutical development; ICH Q9, i.e. Quality Risk Management; ICH Q10, i.e. Pharmaceutical Quality Systems, and FDA's Process Analytical Technology (PAT) were referred to in order to ensure drug product quality. QbD allows formulation and manufacturing variables to be properly understood and controlled.