Mini-review on the phyto-chemistry, pharmacology and toxicology of Cola nitida (Vent.) Schott & Endl. (Malvaceae): A medically interesting bio-resource of multiple purposes in Africa

The purpose of this mini-review was to summarize and update knowledge on the phytochemistry, pharmacology, and toxicity of <i>Cola nitida</i>, with the view of providing baseline data for herbal drug formulation. In January 2021, a non-exhaustive online search of relevant articles was carried out on the phytochemistry, pharmacology, and toxicology of <i>C. nitida</i> from scientifically well-established databases such as Science Direct, PubMed, Web of Science, Scopus, Google Scholar, and SciELO. The plant's scientific name as well as phytochemistry, pharmacology, pharmacognosy, bioactivity and toxicology were used as keywords. The chemical structures of the compounds isolated from this plant were drawn using ChemBioDraw Ultra 12.0 software. A literature survey has revealed that <i>C. nitida</i> is highly appreciated by African populations in various cultures, especially in West Africa. Phytochemical analyses showed that <i>C. nitida</i> contains interesting compounds like catechin, caffeine, epicatechin, polyphenols, alkaloids, tannins, saponins, bromelain, cardenolides, proanthocyanidins, triterpenes, glycosides, flavonoids, anthraquinones, steroids, anthocyanins, glycosides, alkaloids, etc. The presence of these phyto-compounds in the investigated plant species justifies its used as an antimicrobial, anti-malarial, anti-inflammatory, anti-diabetic, anti-coagulant agent. Thus, <i>C. nitida</i> could be used as a raw material for manufacturing efficient medication against various diseases, including sickle cell disease.

Ethanol Exposure During the Intravenous Administration of Chemotherapeutic Drugs: An Analysis of Clinical Practice and a Literature Review

PURPOSE: Injectable cytotoxics may be formulated with ethanol. This study sought to quantify the amount of ethanol exposure during chemotherapy infusions. MATERIALS AND METHODS: We first reviewed the antineoplastic drugs (Anatomical Therapeutic and Chemical code L01) and oncologic supportive care drugs (eg, antiemetics) currently available in France, to identify preparations containing ethanol. The amount of ethanol in the final chemotherapy preparation was calculated. Next, we performed a 2-year, single-center, retrospective analysis of injectable antineoplastic drug compounding in routine clinical practice in a French university medical center. Finally, we reviewed our results with regard to the literature data. RESULTS: Ten of the 60 cytotoxic products on the market contained ethanol at concentrations of up to 790 mg/mL, depending on the drug, formulation, and supplier. Several final preparations contained more than 3 g of ethanol per infusion (the maximum recommended by the European Medicines Agency); this was notably the case for gemcitabine, paclitaxel (up to 20 g ethanol per injection, for both), and etoposide (up to 50 g ethanol per infusion). The analysis of our compounding activity showed that 3,172 (4.99%) of the 63,613 chemotherapy preparations (notably paclitaxel) contained more than 3 g of ethanol. None of the oncologic supportive care drugs contained ethanol. CONCLUSION: Patients are exposed to ethanol during the infusion of antineoplastic drugs. With a view to better patient care, physicians and pharmacists should carefully evaluate the risk of ethanol exposure throughout the course of cytotoxic drug treatment.

Evaluation of Excipient Risk in BCS Class I and III Biowaivers

The objective of this review article is to summarize literature data pertinent to potential excipient effects on intestinal drug permeability and transit. Despite the use of excipients in drug products for decades, considerable research efforts have been directed towards evaluating their potential effects on drug bioavailability. Potential excipient concerns stem from drug formulation changes (e.g., scale-up and post-approval changes, development of a new generic product). Regulatory agencies have established in vivo bioequivalence standards and, as a result, may waive the in vivo requirement, known as a biowaiver, for some oral products. Biowaiver acceptance criteria are based on the in vitro characterization of the drug substance and drug product using the Biopharmaceutics Classification System (BCS). Various regulatory guidance documents have been issued regarding BCS-based biowaivers, such that the current FDA guidance is more restrictive than prior guidance, specifically about excipient risk. In particular, sugar alcohols have been identified as potential absorption-modifying excipients. These biowaivers and excipient risks are discussed here.

Flux-Based Formulation Development—A Proof of Concept Study

The work aimed to develop the Absorption Driven Drug Formulation (ADDF) concept, which is a new approach in formulation development to ensure that the drug product meets the expected absorption rate. The concept is built on the solubility-permeability interplay and the rate of supersaturation as the driving force of absorption. This paper presents the first case study using the ADDF concept where not only dissolution and solubility but also permeation of the drug is considered in every step of the formulation development. For that reason, parallel artificial membrane permeability assay (PAMPA) was used for excipient selection, small volume dissolution-permeation apparatus was used for testing amorphous solid dispersions (ASDs), and large volume dissolution-permeation tests were carried out to characterize the final dosage forms. The API-excipient interaction studies on PAMPA indicated differences when different fillers or surfactants were studied. These differences were then confirmed with small volume dissolution-permeation assays where the addition of Tween 80 to the ASDs decreased the flux dramatically. Also, the early indication of sorbitol’s advantage over mannitol by PAMPA has been confirmed in the investigation of the final dosage forms by large-scale dissolution-permeation tests. This difference between the fillers was observed in vivo as well. The presented case study demonstrated that the ADDF concept opens a new perspective in generic formulation development using fast and cost-effective flux-based screening methods in order to meet the bioequivalence criteria.

Septilin, A Polyherbal Formulation Against the Immunosuppression Induced by Cyclophosphamide and Cisplatin in Swiss Albino Mice

Background: Septilin (Spt) is an ayurvedic drug formulation from Himalaya Drug Company and is well-known for its antibacterial, anti-inflammatory and immunomodulatory activities. Interest in the use of medicinal plants and herbal medicine as immunomodulators has currently been the subject of scientific investigation worldwide. Cyclophosphamide (CP) and Cisplatin (Csp) are widely used chemotherapeutic drugs and are known for their immunosuppressive effects. Methods: The present study evaluated the immune-stimulating activity of Spt (125, 250 and 500 mg/kg; PO/7 days) against CP (50 mg/kg) and Csp (10 mg/kg) induced immunosuppression in mice sensitized with sheep Red Blood Cells (RBC) by measuring Hemagglutination Antibody (HA) titre values and by determining the haematological parameters, such as Haemoglobin (Hb) content, White Blood Cells (WBC), RBC and platelet counts. Thymus index and differential counts of leukocytes were also determined. Results: Upon HA assay, the titre was significantly decreased in CP (59.40%) and Csp (62.16%) in the treatment groups (P<0.001). An increase in the HA titre value in Spt-treated mice showed the stimulation of humoral immune response (P<0.001). The results of haematological study in Spt-treated mice indicated stimulation of total leukocytes, RBC and platelet counts. Moreover, Spt treatment prior to the administration of CP and Csp prevented the loss of body weight and minimized their adverse effect on the mice thymus. Conclusion: Our experimental evidence suggests the immunostimulatory potency of Spt against the immunosuppression induced by chemotherapeutic drugs in mice. The study results are comparable with the immune-potentiating effects of standard immunomodulatory drug Levamisole (Lev). Hence, Spt may be used as an adjuvant to obviate the immune suppression induced by chemotherapeutic medications.

The Essential Properties of Nanoemulsions

Nanoemulsions are a submicron with colloidal particulate systems ranging from 10 to 1,000 nm in size. Nanoemulsions hold enormous scope in the field of cosmetics, diagnostics, food, and paint. Moreover, nanoemulsions are ubiquitously regarded as superior drug carriers for the infusion of lipophilic cytotoxic antineoplastic agents on a particular target criterion. Nanoemulsions are prepared from two immiscible liquids that are mixed by employing surfactants and co-surfactants. It also encompasses some significant benefits like biocompatibility, non-immunogenicity, low toxicity, drug entrapment, nanoscale size, large surface area, long-term and restrained release, uncomplicated mode of formulation, as well as thermodynamic stability. Nanoemulsion drug delivery can address the major challenge of effective drug formulation due to its instability and poor solubility in the vehicle. The primary objective of this chapter is to provide a quick overview of various physico-properties of nanoemulsion, with a special emphasis on its various applications in various fields.

Interaction of Nootropic Drugs with Neurotransmitter Enzyme Acetylcholinesterase: An Insilico Approach: A Review

Nootropic drugs are the class of drugs or supplements that are claimed to enhance cognitive functions, specifically executive functions, memory and creativity in healthy individual. They are sometime referred as cognitive enhancers or smart drugs as they are associated with memory improvement functioning. Some of them are well known drugs and clinically approved by the Food and Drug Administration (FDA). All metabolic reactions are purely dependent on enzymatic actions as they play a very important role in regulating and maintaining most of the biological responses and various processes. An enzyme Acetylcholinesterase (AChE) seems to play an essential role in the conduction of cholinergic brain synapses and neuromuscular junctions. There have been different nootropic drugs identified and approved for curing neurodegenerative disorders such as Alzheimer, Parkinson and Huntington's disease. Their binding efficiency and energy have been well studied an established by using the in-silico docking tools. There are different docking tools available today for analysis of molecules such as PyRx, Auto dock and schrodinger suite. The advent of these tools is being widely used by the pharmaceutical industries for the virtual screening of the formulated drugs against the desired target molecule. It has made the drug formulation process more time efficient and cost effective. Thus, an in-silico approach has been widely accepted for drug discovery and its design.

Long-term non-invasive drug treatments for adult zebrafish

Zebrafish embryos are widely used for drug-discovery however administering drugs to adult zebrafish is limited by current protocols that can cause stress. Here, we develop a drug formulation and administration method for adult zebrafish by producing food-based drug pellets which are consumed voluntarily. We apply this to zebrafish with BRAF-mutant melanoma, a model that has significantly advanced our understanding of melanoma progression, but not of drug resistance due to the limitations of current treatment methods. Short-term, precise, and daily dosing with drug-pellets made with the BRAFV600E inhibitor, vemurafenib, led to tumour regression. On-target drug efficacy was determined by phospho-ERK staining. Continued drug treatment led to the emergence, for the first time in zebrafish, of acquired drug resistance and melanoma relapse, modelling the responses seen in melanoma patients. This method presents a controlled, non-invasive approach that permits long-term drug studies, and can be widely applied to any adult zebrafish model.

An overview of Natural Superdisintegrants

The oral route is the most convenient route of administration for various drugs. It is viewed as the most convenient, most secure, and economical route for patients. Fast disintegrating tablets are popular these days as they disintegrate in the mouth within a few seconds without the use of water. The burdens of regularly used medications in pediatric and geriatric patients have been overwhelmed by quick-dissolving tablets. Natural superdisintegrants have been used for fast-dissolving tablets because they are biodegradable, chemically inert, non-harmful, more affordable, and generally accessible. Natural polymer improves the properties of the tablet as it is commonly used as diluents and binders. Natural super disintegrants decrease the release time and give healthful results to the patients. Most polymers are obtained from nature, they are cost-effective, non-toxic, and non-irritants. Disintegration is the most important step for releasing the drug from the tablet matrix to decrease the disintegration time. In this, drug and polymers come in contact with water, it swells, hydrate, and react chemically to release the drug in the mouth and gastrointestinal tract. Superdisintegrants are those substances that encourage the quick breaking down with a lesser amount contrasted with disintegrants. The quick disintegrants tablets are set up by utilizing suitable polymers which rely on the Physico-chemical properties of drugs and excipients, for example, drug and polymer compatibility, hardness and thickness of tablet, nature of drug and excipients, PH of drug and release parameters of drug formulation. Superdisintegrants are the vehicles added to tablet formulation to advance the breaking of tablets and capsules into small microparticles in aqueous media resulting in to increase in the surface area and promote quick drug release. The disintegrants have a significant capacity to oppose the efficacy of tablet binders and compression forces to form the tablet. Commonly there are three methods to incorporate disintegrants into the tablet: A. Inner addition, B. External expansion, C. Internal, and external addition. Most of the regularly based tablets are those expected to be swallow, disintegrate and release medicaments in the gastrointestinal tract but over a while tablets are manufactured to deliver medicaments in the mouth and gastrointestinal tract within few seconds of swallowing. It has been demonstrated that characteristic polymers are more effective than synthetic polymers. Some research is going to develop safe and effective medication with super disintegrating agents that can be dissolved rapidly to treat the disease.

Bacteriomimetic Liposomes Improve Antibiotic Activity of a Novel Energy-Coupling Factor Transporter Inhibitor

Liposomes have been studied for decades as nanoparticulate drug delivery systems for cytostatics, and more recently, for antibiotics. Such nanoantibiotics show improved antibacterial efficacy compared to the free drug and can be effective despite bacterial recalcitrance. In this work, we present a loading method of bacteriomimetic liposomes for a novel, hydrophobic compound (HIPS5031) inhibiting energy-coupling factor transporters (ECF transporters), an underexplored antimicrobial target. The liposomes were composed of DOPG (18:1 (Δ9-cis) phosphatidylglycerol) and CL (cardiolipin), resembling the cell membrane of Gram-positive Staphylococcus aureus and Streptococcus pneumoniae, and enriched with cholesterol (Chol). The size and polydispersity of the DOPG/CL/± Chol liposomes remained stable over 8 weeks when stored at 4 °C. Loading of the ECF transporter inhibitor was achieved by thin film hydration and led to a high encapsulation efficiency of 33.19% ± 9.5% into the DOPG/CL/Chol liposomes compared to the phosphatidylcholine liposomes (DMPC/DPPC). Bacterial growth inhibition assays on the model organism Bacillus subtilis revealed liposomal HIPS5031 as superior to the free drug, showing a 3.5-fold reduction in CFU/mL at a concentration of 9.64 µM. Liposomal HIPS5031 was also shown to reduce B. subtilis biofilm. Our findings present an explorative basis for bacteriomimetic liposomes as a strategy against drug-resistant pathogens by surpassing the drug-formulation barriers of innovative, yet unfavorably hydrophobic, antibiotics.