Management of Children Admitted to Hospitals across Bangladesh with Suspected or Confirmed COVID-19 and the Implications for the Future: A Nationwide Cross-Sectional Study

There is an increasing focus on researching children admitted to hospital with new variants of COVID-19, combined with concerns with hyperinflammatory syndromes and the overuse of antimicrobials. Paediatric guidelines have been produced in Bangladesh to improve their care. Consequently, the objective is to document the management of children with COVID-19 among 24 hospitals in Bangladesh. Key outcome measures included the percentage prescribed different antimicrobials, adherence to paediatric guidelines and mortality rates using purposely developed report forms. The majority of 146 admitted children were aged 5 years or under (62.3%) and were boys (58.9%). Reasons for admission included fever, respiratory distress and coughing; 86.3% were prescribed antibiotics, typically parenterally, on the WHO ‘Watch’ list, and empirically (98.4%). There were no differences in antibiotic use whether hospitals followed paediatric guidance or not. There was no prescribing of antimalarials and limited prescribing of antivirals (5.5% of children) and antiparasitic medicines (0.7%). The majority of children (92.5%) made a full recovery. It was encouraging to see the low hospitalisation rates and limited use of antimalarials, antivirals and antiparasitic medicines. However, the high empiric use of antibiotics, alongside limited switching to oral formulations, is a concern that can be addressed by instigating the appropriate programmes.

A Systematic Review of the Stability of Extemporaneous Pediatric Oral Formulations

Background. Extemporaneous compounding is a pharmacy practice to produce suitable pharmaceutical preparations when there are no commercially available, licensed, and age-specific dosage forms. Compared to the use of authorized drugs, these preparations have significant risks. Stability issues are one of the major concerns during the preparation of extemporaneous formulations. Aim. The aim of this work was to study the stability of pediatric extemporaneous formulations of commercially available conventional solid dosage forms by reviewing systematically the currently available stability studies. Method. Articles were searched in the databases of the Web of Science, PubMed, Scopus, EMBASE, Cochrane Library, and Google Scholar. From all the searched articles, a total of 28 experimental studies reporting the stability of oral pediatric extemporaneous formulations were included based on the inclusion criteria. Oral extemporaneous formulations from commercially available dosage forms and pure drugs were considered. According to the United States and British Pharmacopeia (USP and BP), most extemporaneous formulations are accepted as chemically stable if they maintain ≥90% of the original drug amount, physically stable if there is no apparent change in physical property, and microbiologically stable if there is no growth of microorganisms in prepared formulations. Finding. In this study, most extemporaneous pediatric oral formulations were chemically, physically, and microbiologically stable and retained more than 90% of the initial content. Very few studies did not include either a physical stability test or a microbiological stability test. Conclusion. According to this systematic review, the chemical and physical instabilities as well as microbial growth on pediatric oral extemporaneous formulations are very rare in published experimental studies. Most studies show that extemporaneous preparations are stable at the ICH recommended storage conditions and duration. Generally, extemporaneously prepared oral formulations will be the promising option for child medications.

The Development of Third-Generation Tetracycline Antibiotics and New Perspectives

The tetracycline antibiotic class has acquired new valuable members due to the optimisation of the chemical structure. The first modern tetracycline introduced into therapy was tigecycline, followed by omadacycline, eravacycline, and sarecycline (the third generation). Structural and physicochemical key elements which led to the discovery of modern tetracyclines are approached. Thus, several chemical subgroups are distinguished, such as glycylcyclines, aminomethylcyclines, and fluorocyclines, which have excellent development potential. The antibacterial spectrum comprises several resistant bacteria, including those resistant to old tetracyclines. Sarecycline, a narrow-spectrum tetracycline, is notable for being very effective against Cutinebacterium acnes. The mechanism of antibacterial action from the perspective of the new compound is approached. Several severe bacterial infections are treated with tigecycline, omadacycline, and eravacycline (with parenteral or oral formulations). In addition, sarecycline is very useful in treating acne vulgaris. Tetracyclines also have other non-antibiotic properties that require in-depth studies, such as the anti-inflammatory effect effect of sarecycline. The main side effects of modern tetracyclines are described in accordance with published clinical studies. Undoubtedly, this class of antibiotics continues to arouse the interest of researchers. As a result, new derivatives are developed and studied primarily for the antibiotic effect and other biological effects.

Formulation and Evaluation of Orodispersible Tablet of poorly water Soluble Drug ‘Fenofibrate’ by Using Solubility Enhancement Technique

In the recent years scientific and technological advancements have been made in the research and development of oral drug delivery systems. The aim of this study was to formulate and evaluate of orodispersible tablets by direct compression for fenofibrate by using super fast disintegrating agents like croscarmellose sodium. The use of super disintegrant and excipient for preparation of fast disintegrating is highly effective and commercially feasible. In the present investigation poorly water soluble drug is one of the most important parameters of oral formulations sucessfully developed fenofibrate was using solvent evaporation method drug: PEG 6000 in (1:5 w/w). The formulation F7 was the optimized formula that showed satisfactory results with various physicochemical evaluation parameters like thickness, hardness, weight variation, friability, drug content, % drug release almost 79.98% within 15 min. and it was follow the maximum higuchi release kinetics that regression coefficient values ‘r2’= 0.995.

Combined Methodologies for Determining In Vitro Bioavailability of Drugs and Prediction of In Vivo Bioequivalence From Pharmaceutical Oral Formulations

With the aim of developing an in vitro model for the bioavailability (BA) prediction of drugs, we focused on the study of levonorgestrel (LVN) released by 1.5 mg generic and brand-name tablets. The developed method consisted in combining a standard dissolution test with an optimized parallel artificial membrane permeability assay (PAMPA) to gain insights into both drug release and gastrointestinal absorption. Interestingly, the obtained results revealed that the tablet standard dissolution test, combined with an optimized PAMPA, highlighted a significant decrease in the release (15 ± 0.01 μg min−1 vs 30 ± 0.01 μg min−1) and absorption (19 ± 7 × 10–6 ± 7 cm/s Pe vs 41 ± 15 × 10–6 cm/s Pe) profiles of a generic LVN tablet when compared to the brand-name formulation, explaining unbalanced in vivo bioequivalence (BE). By using this new approach, we could determine the actual LVN drug concentration dissolved in the medium, which theoretically can permeate the gastrointestinal (GI) barrier. In fact, insoluble LVN/excipient aggregates were found in the dissolution media giving rise to non-superimposable dissolution profiles between generic and brand-name LVN tablets. Hence, the results obtained by combining the dissolution test and PAMPA method provided important insights confirming that the combined methods can be useful in revealing crucial issues in the prediction of in vivo BE of drugs.

Warfarin Sodium Stability in Oral Formulations

Warfarin sodium is a low-dose pharmaceutical blood thinner that exists in two forms: the clathrate form and the amorphous form. In commercially available warfarin sodium oral suspension, the active pharmaceutical ingredient (API) is added in the amorphous state. This study investigates the apparent instability of the commercially available warfarin liquid oral formulation using Raman and IR spectroscopy, X-ray diffraction, differential scanning calorimetry, UV spectroscopy, and optical microscopy. Warfarin, not its sodium salt, was identified as the undissolved solid existing in the suspension. This was found to be due to the dissociation of sodium salt and the protonation of the warfarin ion in the liquid phase, which triggered the crystallization of the sparingly soluble unsalted form. The coexistence of protonated and unprotonated warfarin ions in the supernatant, as detected by Raman and UV spectroscopy, confirmed this assumption. Study of the dissolution of warfarin sodium amorphous salt and crystalline sodium clathrate in the placebo and pure water verified the results. The effect of pH and temperature on warfarin precipitation was also explored.

Progesterone Metabolism by Human and Rat Hepatic and Intestinal Tissue

Following oral administration, the bioavailability of progesterone is low and highly variable. As a result, no clinically relevant, natural progesterone oral formulation is available. After oral delivery, first-pass metabolism initially occurs in the intestines; however, very little information on progesterone metabolism in this organ currently exists. The aim of this study is to investigate the contributions of liver and intestine to progesterone clearance. In the presence of NADPH, a rapid clearance of progesterone was observed in human and rat liver samples (t1/2 2.7 and 2.72 min, respectively). The rate of progesterone depletion in intestine was statistically similar between rat and human (t1/2 197.6 min in rat and 157.2 min in human). However, in the absence of NADPH, progesterone was depleted at a significantly lower rate in rat intestine compared to human. The roles of aldo keto reductases (AKR), xanthine oxidase (XAO) and aldehyde oxidase (AOX) in progesterone metabolism were also investigated. The rate of progesterone depletion was found to be significantly reduced by AKR1C, 1D1 and 1B1 in human liver and by AKR1B1 in human intestine. The inhibition of AOX also caused a significant reduction in progesterone degradation in human liver, whereas no change was observed in the presence of an XAO inhibitor. Understanding the kinetics of intestinal as well as liver metabolism is important for the future development of progesterone oral formulations. This novel information can inform decisions on the development of targeted formulations and help predict dosage regimens.