Clinical Pharmacology of Glucagon.

Glucagon was discovered about a hundred years ago and its role in health and disease is under continuous investigation. Glucagon is a counter regulatory hormone secreted by alpha cells of the pancreas in response to multiple stimuli. Although some of glucagon's actions and its clinical application have been described, clinical experience with glucagon has been historically overshadowed by that of insulin. To date, the role of glucagon's actions in pharmacotherapy has been under explored. Glucagon plays a considerable role as a hormonal regulator via its known actions on the liver. The rise in obesity and diabetes mellitus prevalence is bringing focus to glucagon's known physiological roles and possible clinical applications. Six glucagon products and a glucagon analog are approved for use in the United States. Clinical pharmacology studies provide crucial support of glucagon's actions as evident from comprehensive pharmacokinetics and pharmacodynamics evaluations in humans. Here, we briefly describe the established physiological role of glucagon in humans and its known relationship with disease. We later summarize the clinical pharmacology of available glucagon products with different routes of administration.

Pharmaceutical Polygon Fingerprinting Matrix System (PharmP-FM): A Potential Tool for Pharmaceutical Quality Control.

Background & Purpose A new discriminatory system for evaluating the quality of pharmaceuticals is described in this paper as the Pharmaceutical Polygon Fingerprint Matrix system (PharmP-FM). To assess the quality of various pharmaceutical formulations and dosage forms, PharmP-FM uses both qualitative and quantitative fingerprinting techniques. The system expands on the SeDeM expert system, which was initially created to evaluate the suitability of powder for direct compression. PharmP-FM creates a graphical representation of the product's pharmaceutical quality using a set of input parameters. The Performance Index (PI), Normalized Parameter Index (NPI), and Formulation Index (FI) are among the system's output parameters. Methods To evaluate PharmP-FM's performance, the paper examines its application in assessing batch-to-batch variability of weight loss supplement capsules and the quality of multisource brand products of levothyroxine tablets. The findings demonstrate PharmP-FM's capability to identify variations in pharmaceutical quality across these products. Results & Conclusion This paper concludes that PharmP-FM exhibits potential promise as a pharmaceutical quality assessment tool. Its user-friendly nature and adaptability to different formulations and dosage forms make it a versatile discriminatory system. Additionally, PharmP-FM is an open-ended and scalable system that can incorporate additional parameters and accommodate products of varying complexities. The study's results strongly suggest its potential as a potential tool for pharmaceutical quality assessment.

Chitosan Nanoparticles Alleviated the Adverse Effects of Sildenafil on the Oxidative Stress Markers and Antioxidant Enzyme Activities in Rats.

Sildenafil (SF) is widely used for erectile dysfunction and other conditions, though with limitations regarding oral absorption and adverse effects. Despite nanotechnological improvements, the effect of nanocarriers on SF hepatotoxicity has not been documented to date. This study aimed at assessing the impact of chitosan nanoparticles either uncoated (CS NPs) or Tween 80-coated (T-CS NPs) on the effects of SF on oxidative stress markers and antioxidant enzyme activities in rats. Test SF-CS NPs prepared by ionic gelation were uniform positively charged nanospheres (diameter 178-215 nm). SF was administered intraperitoneally to male rats (1.5 mg/kg body weight) in free or nanoencapsulated forms as SF-CS NPs and T-SF-CS NPs for 3 weeks. Free SF significantly suppressed the activity of the antioxidant enzymes glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD), as well as the levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) as in an indirect measure of free radicals. Interestingly, SF-CS NPs and T-SF-CS-NPs treatments significantly attenuated the inhibitory effects of SF on the activity of these enzymes whereas, GST activity was inhibited. Moreover, the protein expression of GST was downregulated upon treatment of rats with free SF, SF-CS-NPs, and T-SF CS-NPs. In contrast, the activity and protein expression of GPx was induced by SF-CS NPs and T-SF-CS-NPs treatments. The histopathological study showed that SF induced multiple adverse effects on the rat liver architecture which were markedly suppressed particularly by T-SF-CS NPs. In conclusion, chitosan nanoencapsulation of SF counteracted the adverse effects of SF on the activity of antioxidant enzymes and liver architecture. Findings might have significant implications in improving the safety and efficacy of SF treatment of the widely expanding disease conditions.

Mobile-Based Augmented Reality Application in Pharmacy Schools Implemented in Pharmaceutical Compounding Laboratories: Students' Benefits and Reception.

BACKGROUND: Augmented reality (AR) is a technological approach which combines virtual objects such as text, pictures or videos with physical objects (real-world). The study aimed to design, implement and validate a mobile-based AR application, as a self-paced, interactive, student-centered learning tool be used in the pharmaceutical compounding laboratory course for first year pharmacy students. METHOD: A mobile-based AR application (Amplified Rx app; HeyPayLess Inc) compatible with iOS and android operating system was developed. A cross-over study design was conducted where alternatively, one group was subjected to ARx app implementation in 8 formulations and the other group served as control. The reception and benefits to students were assessed via a 10 questions survey. In this case, 69 (2019) and 55 (2020) students participated in the study. RESULT: Students' use of ARx app was increased in 2020 which indicates its usefulness. For acceptability, leaners enjoyed interactive materials and tutorial videos were the most used and appealing item. Learners described the installation, scanning and operation to be very easy in both years. 86.95% of learners were confident conducting the experiments with the assistance of ARx app in 2019 and increased to 92.73% in 2020. 33.33% considered ARx app to be the most helpful resource in 2019, and the percent was significantly increased to 76.36% in 2020. CONCLUSION: AR technology implementation in pharmaceutical education could create student-centered engaging and interactive learning experience in fundamental areas such as pharmaceutical compounding laboratories.

3D-Printed Microfluidics Potential in Combating Future and Current Pandemics (COVID-19).

Coronavirus disease (COVID-19) emerged in China in December 2019. In March 2020, the WHO declared it a pandemic leading to worldwide lockdowns and travel restrictions. By May, it infected 4,789,205 and killed 318,789 people. This led to severe shortages in the medical sector besides devastating socio-economic effects. Many technologies such as artificial intelligence (AI), virtual reality (VR), microfluidics, 3D printing, and 3D scanning can step into contain the virus and hinder its extensive spread. This article aims to explore the potentials of 3D printing and microfluidic in accelerating the diagnosis and monitoring of the disease and fulfilling the shortages of personal protective equipment (PPE) and medical equipment. It highlights the main applications of 3D printers and microfluidics in providing PPE (masks, respirators, face shields, goggles, and isolation chambers/hoods), supportive care (respiratory equipment) and diagnostic supplies (sampling swabs & lab-on-chip) to ease the COVID-19 pressures. Also, the cost of such technology and regulation considerations are addressed. We conclude that 3D printing provided reusable and low-cost solutions to mitigate the shortages. However, safety, sterility, and compatibility with environmental protection standards need to be guaranteed through standardization and assessment by regulatory bodies. Finally, lessons learned from this pandemic can also help the world prepare for upcoming outbreaks.

Enhanced Multiscale Principal Component Analysis for Improved Sensor Fault Detection and Isolation.

Multiscale PCA (MSPCA) is a well-established fault-detection and isolation (FDI) technique. It utilizes wavelet analysis and PCA to extract important features from process data. This study demonstrates limitations in the conventional MSPCA fault detection algorithm, thereby proposing an enhanced MSPCA (EMSPCA) FDI algorithm that uses a new wavelet thresholding criterion. As such, it improves the projection of faults in the residual space and the threshold estimation of the fault detection statistic. When tested with a synthetic model, EMSPCA resulted in a 30% improvement in detection rate with equal false alarm rates. The EMSPCA algorithm also relies on the novel application of reconstruction-based fault isolation at multiple scales. The proposed algorithm reduces fault smearing and consequently improves fault isolation performance. The paper will further investigate the use of soft vs. hard wavelet thresholding, decimated vs. undecimated wavelet transforms, the choice of wavelet decomposition depth, and their implications on FDI performance.The FDI performance of the developed EMSPCA method was illustrated for sensor faults. This undertaking considered synthetic data, the simulated data of a continuously stirred reactor (CSTR), and experimental data from a packed-bed pilot plant. The results of these examples show the advantages of EMSPCA over existing techniques.

Microneedle-Based Vaccine Delivery: Review of an Emerging Technology.

Vaccination has produced a great improvement to the global health by decreasing/eradicating many infectious diseases responsible for significant morbidity and mortality. Thanks to vaccines, many infections affecting childhood have been greatly decreased or even eradicated (smallpox, measles, and polio). That is why great efforts are made to achieve mass vaccination against COVID-19. However, developed vaccines face many challenges with regard to their safety and stability. Moreover, needle phobia could prevent a significant proportion of the population from receiving vaccines. In this context, microneedles (MNs) could potentially present a solution to address these challenges. MNs represent single dose administration systems that do not need reconstitution or cold-chain storage. Being self-administered, pain-free, and capable of producing superior immunogenicity makes them a more attractive alternative. This review explores microneedles' types, safety, and efficacy in vaccine delivery. Preclinical and clinical studies for microneedle-based vaccines are discussed and patent examples are included.

Community pharmacists' needs, education, and readiness in facing COVID-19: Actions & recommendations in Egypt.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) outbreak is considered one of the most important public health crises all over the world and in Egypt. Community pharmacists represent the third largest health care professional group after physicians and nurses. Community pharmacists are expected to be fully prepared at the frontline of defending their community needs by limiting the spread of COVID-19 via different pharmaceutical care services. AIM: This study aimed to evaluate the sources of knowledge and readiness of community pharmacists in facing COVID-19 early outbreak in Egypt. METHODS: A descriptive cross-sectional study was performed via a self-administered online google form questionnaire during the early period from 14 April to 3 June 2020. The questionnaire focused on; evaluating education level, sources of information, and readiness of Egyptian community pharmacists in the COVID-19 pandemic crisis. RESULTS: A total of 318 community pharmacists from Egypt participated in this questionnaire. About half of the surveyed pharmacists reported that they were frequently consulted and that their patients were seeking consultation regarding COVID-19 management more than 10 times per day. More than half of the pharmacists reported using social media as a source of information and knew the right social distancing recommendations. Regarding protective measures, only a quarter of pharmacists disclosed the availability of personal protective equipment (PPE). Nevertheless, the majority of pharmacists significantly reported some initial lack of support either inform of recommendations or PPE supply. CONCLUSION: The study revealed the dependence of community pharmacists on social media as the main source of information and the lack of early awareness of evidence-based practice resources. Community pharmacists were in need of more initial support to achieve better satisfaction, patient counselling and infection control. Corrective measures were promptly undertaken to support and satisfy the Egyptian community pharmacists' initial awareness and readiness facing COVID-19.

The safety, efficacy and pharmaceutical quality of male enhancement nutraceuticals bought online: Truth versus claim.

OBJECTIVE: Nutraceutical products are widely used for their claimed therapeutic benefits. However, falsified or adulterated nutraceuticals present a major health threat to consumers. This study investigates the pharmaceutical quality, safety and anti-inflammatory effects of six male enhancement nutraceuticals that claim to be 100% natural. METHODS: Three batches of six male enhancement products were tested to detect the presence and levels of adulterants via high-performance liquid chromatography (HPLC). The pharmaceutical quality of the selected nutraceuticals was tested with near infrared spectroscopy (NIR) and SeDeM. The cytotoxic effects of these products on HepG2 cells were determined through cell proliferation (XTT) and lactate dehydrogenase (LDH) cytotoxicity assays. Lastly, the in vitro inflammatory effects of these products were investigated using murine J774 macrophages through cytokine release analysis. RESULTS: HPLC analysis detected the presence of sildenafil citrate, a vasodilator, and the active ingredient in Viagra and Revatio, in all batches of the products we analyzed. Amount of sildenafil citrate ranged from 0.45 mg to 51.85 mg among different batches. NIR assessment showed inter- and intra-batch heterogeneity in product composition. Results of the XTT and LDH assays showed significant cytotoxic effects of the analyzed products. XTT analysis revealed that the viability of HepG2 treated with tested products varied from 27.57% to 41.43%. Interestingly, the male enhancement products also showed anti-inflammatory effects. CONCLUSION: Despite their labeling as 100% natural, all products tested in this study contained levels of sildenafil citrate, which was not reported on the packaging. There was a lack of pharmaceutical uniformity among products of the same batch and across different batches. Additionally, the products we tested had cytotoxic effects. These study findings highlight the adulteration, poor quality and hazard of these nutraceuticals. Therefore, strict regulation of these products and standardization of the definition of nutraceuticals are urgently needed. Further, these falsely advertised products should be withdrawn from the market due to potential adverse effects on the health of their consumers.

Berberine Nanoencapsulation Attenuates Hallmarks of Scoplomine Induced Alzheimer's-Like Disease in Rats.

BACKGROUND: Berberine (BBR), an isoquinoline alkaloid, acts as a multipotent active pharmaceutical ingredient to counteract several types of dementia based on its numerous pharmacological actions including antioxidant, anti-inflammatory, cholesterol-lowering effect, and inhibition of Aß production and AChE. However, BBR suffers from poor absorption, bioavailability and brain drug uptake. The present study is directed for the formulation and characterization of Chitosan BBR-Nanoparticles (BBR-NPs) as well as the estimation of its neuroprotective effects against scopolamine induced cognitive impairments. METHODS: BBR-NPs were formulated using the ionic gelation method, and tripolyphosphate was chosen as a crosslinker. Nanoparticles size, zeta potential, encapsulation efficiency and releasing profile were estimated. To investigate the neuroprotective effects, adult fifty-six Wistar male rats were randomly distributed into three control groups, received saline, polyethylene glycol or Chitosan- NPs, respectively; induced group, received scopolamine (2 mg/ kg, i.p.) and three treated groups were orally administrated BBR (50 mg/ kg), BBR- NP (7 mg/ kg) and donepezil (2.25 mg/ kg, as positive control) followed by scopolamine injection after 40 min, daily for 4 weeks. Morris water maze test, oxidative stress parameters, cholinergic and amyloid-ß processing intermediates, as well as neuroplasticity markers and histopathological examination were assessed. RESULTS: Our results showed that BBR- NPs were better than BBR and donepezil as BBR- NPs were powerful inhibitory ligands towards AChE and Aß42 formation and significantly down-regulated Tau, iNOS and BACE gene expression in rats' hippocampus. BBR-NPs administration, at 1/6 of BBR therapeutic recommended dose, significantly improved learning and memory function. This could be accredited to the diminution of oxidative stress and amyloid-ß toxicity in addition to the improvement of the neuroplasticity markers. CONCLUSION: The enhancing effect of BBR- NPs could be related to the enhancing of its bioavailability, absorption and brain drug uptake, which need more investigation in future work.

Current Topical Strategies for Skin-Aging and Inflammaging Treatment: Science versus Fiction.

Aging is a natural phenomenon that affects the whole body, including the skin. As we age, endogenous and exogenous factors cause our skin to become thinner, paler, and wrinkled. Although the underlying mechanisms of the pathogenesis of skin aging are not entirely known, multiple pathways have been proposed. Inflammaging has recently emerged as a pathway that correlates aging and age-related diseases with inflammation. This review discusses the role and pathways of inflammaging that lead to skin aging. Moreover, strategies and current topical approaches for skin-aging treatment are discussed. Studies over the past 10 years suggested that DNA damage and oxidative stress are the most critical mechanisms in skin aging, and both are interlinked with inflammaging. Several treatments for skin aging have been considered such as antioxidants, hormone replacement therapy, and vitamins. To deliver anti-aging agents topically, researchers adopted numerous approaches to enhance skin penetration including physical, chemical, or biomaterial enhancers and carrier-based formulations. In recent years, consumers' demands for anti-aging products have considerably risen, leading to robust growth in the anti-aging market. Therefore, further in-depth studies are necessary to understand skin-aging mechanisms and evaluate the efficacy of anti-aging products to protect consumers worldwide by providing them safe and effective over-the-counter skin-aging formulations.

Nutraceuticals' Novel Formulations: The Good, the Bad, the Unknown and Patents Involved.

Traditional nutraceuticals and cosmeceuticals hold pragmatic nature with respect to their definitions, claims, purposes and marketing strategies. Their definitions are not well established worldwide. They also have different regulatory definitions and registration regulatory processes in different parts of the world. Global prevalence of nutraceuticals and cosmeceuticals is noticeably high with large market share with minimal regulation compared to traditional drugs. The global market is flooded with nutraceuticals and cosmeceuticals claiming to be of natural origin and sold with a therapeutic claim by major online retail stores such as Amazon and eBay. Apart from the traditional formulations, many manufacturers and researchers use novel formulation technologies in nutraceutical and cosmeceutical formulations for different reasons and objectives. Manufacturers tend to differentiate their products with novel formulations to increase market appeal and sales. On the other hand, researchers use novel strategies to enhance nutraceuticals and cosmeceuticals activity and safety. The objective of this review is to assess the current patents and research adopting novel formulation strategies in nutraceuticals and cosmeceuticals. Patents and research papers investigating nutraceutical and cosmeceutical novel formulations were surveyed for the past 15 years. Various nanosystems and advanced biotechnology systems have been introduced to improve the therapeutic efficacy, safety and market appeal of nutraceuticals and cosmeceuticals, including liposomes, polymeric micelles, quantum dots, nanoparticles, and dendrimers. This review provides an overview of nutraceuticals and cosmeceuticals current technologies, highlighting their pros, cons, misconceptions, regulatory definitions and market. This review also aims in separating the science from fiction in the nutraceuticals and cosmeceuticals development, research and marketing.

High-Dose Gabapentin for the Treatment of Severe Alcohol Withdrawal Syndrome: A Retrospective Cohort Analysis.

STUDY OBJECTIVE: Gabapentin has been proved to be beneficial in promoting abstinence, decreasing alcohol cravings, and improving mood and sleep quality when given at higher doses; however, data are limited regarding the efficacy and safety of using high-dose gabapentin as part of the treatment of alcohol withdrawal syndrome (AWS). The aim of this study was to evaluate the impact of high-dose gabapentin on benzodiazepine requirements, alcohol withdrawal symptoms, and hospital length of stay in patients hospitalized with AWS. DESIGN: Retrospective cohort study. SETTING: Large academic medical center. PATIENTS: All adults presenting to the emergency department between January 2015 and April 2018 with a diagnosis of severe AWS (Clinical Institute Withdrawal Assessment for Alcohol Scale, Revised [CIWA-Ar] score ≥ 15) and prescribed the institution's alcohol withdrawal agitated delirium protocol were eligible for inclusion in the study. Of these, 50 patients who received high-dose gabapentin (≥ 1800 mg/day) in the first 48 hours of hospital admission (treatment group) were propensity score-matched to 50 patients who did not receive gabapentin (control group). MEASUREMENTS AND MAIN RESULTS: Patients who received high-dose gabapentin required a significantly lower overall amount of benzodiazepines (mean ± SD 109.5 ± 53.4 mg vs 88.5 ± 35.6 mg [lorazepam equivalents], p=0.023) and had a significantly lower mean CIWA-Ar score (10.1 ± 4.7 vs 7.7 ± 3.9, p=0.010) and maximum CIWA-Ar score (16.0 ± 7.0 vs 12.6 ± 6.1, p=0.016) on day 3 of hospitalization. The high-dose gabapentin regimen was well tolerated, without an increased risk of oversedation, compared with the control group (Richmond Agitation-Sedation Scale score < -1: 34% in the treatment group vs 20% in the control group, p=0.115). Patients receiving high-dose gabapentin had a shorter length of hospital stay (7.4 ± 4.0 days vs 6.0 ± 2.6 days, p=0.034) and increased likelihood of being discharged home (66% vs 88%, p=0.009) compared with the control group. CONCLUSION: Early initiation of high-dose gabapentin was associated with a significant reduction in benzodiazepine exposure, faster stabilization of alcohol withdrawal-related symptoms, and shorter hospital length of stay. Future studies evaluating gabapentin's effect on long-term safety and hospital readmission are warranted.

Integrated continuous manufacturing in pharmaceutical industry: current evolutionary steps toward revolutionary future.

Continuous manufacturing (CM) has the potential to provide pharmaceutical products with better quality, improved yield and with reduced cost and time. Moreover, ease of scale-up, small manufacturing footprint and on-line/in-line monitoring and control of the process are other merits for CM. Regulating authorities are supporting the adoption of CM by pharmaceutical manufacturers through issuing proper guidelines. However, implementation of this technology in pharmaceutical industry is encountered by a number of challenges regarding the process development and quality assurance. This article provides a background on the implementation of CM in pharmaceutical industry, literature survey of the most recent state-of-the-art technologies and critically discussing the encountered challenges and its future prospective in pharmaceutical industry.

Bioconjugation in Drug Delivery: Practical Perspectives and Future Perceptions.

For the past three decades, pharmaceutical research has been mainly converging to novel carrier systems and nanoparticulate colloidal technologies for drug delivery, such as nanoparticles, nanospheres, vesicular systems, liposomes, or nanocapsules to impart novel functions and targeting abilities. Such technologies opened the gate towards more sophisticated and effective multi-acting platform(s) which can offer site-targeting, imaging, and treatment using a single multifunctional system. Unfortunately, such technologies faced major intrinsic hurdles including high cost, low stability profile, short shelf-life, and poor reproducibility across and within production batches leading to harsh bench-to-bedside transformation.Currently, pharmaceutical industry along with academic research is investing heavily in bioconjugate structures as an appealing and advantageous alternative to nanoparticulate delivery systems with all its flexible benefits when it comes to custom design and tailor grafting along with avoiding most of its shortcomings. Bioconjugation is a ubiquitous technique that finds a multitude of applications in different branches of life sciences, including drug and gene delivery applications, biological assays, imaging, and biosensing.Bioconjugation is simple, easy, and generally a one-step drug (active pharmaceutical ingredient) conjugation, using various smart biocompatible, bioreducible, or biodegradable linkers, to targeting agents, PEG layer, or another drug. In this chapter, the different types of bioconjugates, the techniques used throughout the course of their synthesis and characterization, as well as the well-established synthetic approaches used for their formulation are presented. In addition, some exemplary representatives are outlined with greater emphasis on the practical tips and tricks of the most prominent techniques such as click chemistry, carbodiimide coupling, and avidin-biotin system.

Compounding and Comparative Study of a Superior, Faster, and More Adaptable Lidocaine Dental Gel Formulation.

Compounding perfection confirms a safe, swift, and efficacious delivery of personalized compounded medication. A large variability of the potency of the finished product may stem from complicated formulation or difficult-to-adopt methods. Also, the formulation and compounding method may adversely affect the amount of time needed to finish the compounding and dispense the medication for the patient. This study involves the development of a novel formulation and compounding method of lidocaine hydrochloride 2% dental gel and compares it with an older, more common formulation which contains five times more alcohol and four times more gelling material. Student-pharmacists were recruited in this study, and the finished products were compared in terms of their intra-group potency uniformity, time needed to finish the compounding, and post-compounding psychometric feedback by the compounders. Each compounder participated in both of the formulation methods in a crossover fashion. Our result indicates that the new formulation and the associated method enables the compounders to produce products with less variation, requiring statistically significantly less compounding time and better acceptability by the compounder.

Protective effect of surface-modified berberine nanoparticles against LPS-induced neurodegenerative changes: a preclinical study.

Berberine (BBR) exerts documented protection against neurodegenerative disorders. However, data on the effect of nano-encapsulation on the neuroprotective effect of BBR are lacking. We investigated the effect of BBR loading into chitosan (CS) nanoparticles (NPs) and their surface modification with Tween 80 (T80), polyethylene glycol 4000 (PEG), and miltefosine (MFS) against lipopolysaccharide (LPS)-induced neurodegenerative changes in addition to hepatotoxicity in rats. BBR-NPs were prepared by ionic gelation and characterized for morphology by transmission electron microscopy (TEM), colloidal properties, and entrapment efficiency (EE%). The neuroprotective and hepatoprotective effects of a 14-day pretreatment with four BBR-NPs formulations (4 mg/kg BBR/day) by intraperitoneal (i.p.) injection were challenged by a single i.p. 4 mg/kg dose of LPS on the fifteenth day. Neuroprotective efficacy and potential toxicity of BBR-NPs relative to BBR solution were assessed biochemically and histopathologically. One-way ANOVA followed by Tukey's comparison test was used for statistical analysis. CS nano-encapsulation and surface modification of BBR-NPs altered the neuroprotective and hepatoprotective effects of BBR depending on the physicochemical and/or biological effects of BBR, CS, coating materials, and NP-related features. Similar to the prophylactic and treatment efficacy of NPs for brain delivery, safety of these nanostructures and their individual formulation components warrants due research attention.

Over-the-Counter Herbal Weight Loss Supplements in Egypt: Label Claim, Microbiological and Pharmaceutical Quality, and Safety Assessments.

OBJECTIVES: Nutraceuticals are advertised and sold with the label claim of being natural and safe herbal products. Due to the absence of clear regulations and guidelines for safety assessments of these products, nutraceuticals are commonly adulterated in order to increase sales. The objective of the current study was to design a comprehensive evaluation system to assess the safety, efficacy, authenticity according to label claim, and pharmaceutical quality of herbal slimming products in between 2015 and 2017. METHODS: We designed a comprehensive assessment system to evaluate the safety, authenticity according to label claim, and pharmaceutical quality of slimming nutraceuticals. Six different popular products were evaluated (Zotreem Plus®, Zotreem Extra®, Malaysian Super Slim®, AB Slim®, Chinese Super Slim®, and Metabolites®). The pharmaceutical evaluation included analyzing the samples via high-performance liquid chromatography to determine any possible adulterants. Additionally, the products' physical properties were assessed via pharmacopeial tests. Finally, a microbial evaluation and a cross-sectional observational retrospective prevalence study were conducted to assess the products' safety and efficacy. -Results: The tested products were found to be adulterated with unreported active pharmaceutical ingredients such as sibutramine, sildenafil, phenolphthalein, and orlistat. Furthermore, they contained heterogeneous amounts of adulterants and exhibited an unsatisfactory pharmaceutical and microbial quality. Finally, the observational survey conducted on users showed that high percentages of participants suffered from common side effects such as depression, diarrhea, and hypertension. CONCLUSIONS: These products threaten the health of consumers. There is a need to raise awareness of the lethal consequences of illegal nutraceuticals.

Kernel Generalized Likelihood Ratio Test for Fault Detection of Biological Systems.

In this paper, we develop an improved fault detection (FD) technique in order to enhance the monitoring abilities of nonlinear biological processes. Generalized likelihood ratio test (GLRT)-based kernel principal component analysis (KPCA) (called also kernel GLRT) is an effective data-driven technique for monitoring nonlinear processes. However, it is well known that the data collected from complex and multivariate processes are multiscale due to the variety of changes that could occur in process with different localization in time and frequency. Thus, to enhance the process monitoring abilities, we propose to combine the advantages of kernel GLRT and multiscale representation using wavelets by developing a multiscale kernel GLRT (MS-KGLRT) detection chart. The proposed fault detection approach is addressed so that the KPCA is used to compute the model in the feature space and the MS-KGLRT chart is applied to detect the faults. The detection performance of the new chart is studied using two examples, one using synthetic data and the other using biological process representing a Cad System in E. Coli (CSEC) model for detecting small and moderate shifts (offset or bias and drift). The MS-KGLRT chart is used to enhance fault detection of the CSEC model through monitoring some of the key variables involved in this model such as enzymes, lysine, and cadaverine.

Effect of batch age on potency and dissolution of levothyroxine sodium tablets: impact of BP and USP monograph differences on dissolution results.

Controversies surround levothyroxine sodium as a drug and product, and are reflected in compendia (USP vs BP) differences in levothyroxine sodium tablets specifications concerning potency limit and dissolution test conditions, and in lack of consensus on several issues such as whether the drug BCS class I or III. We have recently published a clinical study in patients comparing the efficacy of multisource 100 mcg levothyroxine sodium tablets (three sources, two brands, a total of five batches). Clinical efficacy and dissolution rate data varied among the tablet batches studied and indicated that brand/source interchangeability could not be claimed. The efficacy parameters showed good correlation with dissolution data generated under BP 2014, but not under USP 2014 dissolution test conditions. In the present study, we decided to expand the number of tablet batches studied in vitro to a total of 12, to report potency and content uniformity data missing in the clinical study, and to further examine the discrepancy in dissolution results based on the medium used. The wide range of batch age in the studied samples allowed investigating the effect of batch age on in-vitro tablet performance parameters. Generated potency values indicated the prevalence of super-potent tablet batches. The dissolution data reflected the effect of compendia monograph differences in dissolution medium. The results also indicated an inverse relationship between tablet potency and batch age and, between dissolution and batch age. The possible effect of potency results on the generated dissolution data was discussed. Statistical significance of correlations examined was assessed by linear and non-linear regression analysis. Statistical significance was evident for the relation between batch age and BP 2014 dissolution data, compared to USP 2014 dissolution results.