Nanocrystals- A substantial platform for drug delivery applications.

Poor solubility of a drug is one of the major concerns in drug delivery. Many strategies have been employed for solving this problem, but there are still some deficiencies with current strategies, such as low drug loading, high toxicity, poor stability, potential drug loss during storage and complex manufacturing method. By formulating nanocrystals, problems associated with the delivery of drugs with low water or lipid solubility can be addressed. Unlike polymeric nanoparticles and lipidic nanoparticles, they are not a reservoir or matrix system. Nanocrystals are colloidal suspensions of nanosized particles stabilized by polymeric or electrostatic stabilization. They can be prepared by Top-down or Bottom-up approaches. Some of the methods for the preparation of nanocrystals are nanoprecipitation, media milling, high-pressure homogenization, emulsions and microemulsions as templates, supercritical fluid technology and co-grinding. They can be used for oral, intravenous, ocular, inhalation, intramuscular drug delivery and drug targeting.

Synthesis of rutin derivatives to enhance lipid solubility and development of topical formulation with a validated analytical method

Background: Rutin is available on the market as a topical formulation for the treatment of several conditions, such as internal bleeding, hemorrhoids, and varicose veins. However, these gels have low solubility and limited bioavailability due to their decreased lipid solubility. Objective: In this study, we aimed to synthesize potentially novel lipophilic rutin prodrugs. The suggested library of these rutin prodrugs includes changing the solubility profile to facilitate rutin transport across biological barriers, thereby improving drug delivery through topical application. Methods: Six rutin derivatives were synthesized based on the ester prodrug strategy. The synthesized compounds were formulated as topical ointments, and their permeability via Franz diffusion was measured. An ultraviolet (UV) analytical method was developed in our laboratories to quantify rutin derivatives both as raw materials and in final dosage forms. The analytical method was then validated. Result: The results of Franz diffusion analyses showed that transdermal permeability increased by 10_Fo.jpgl height=""d for decaacetylated rutin compared to the other esterified rutins. A simple analytical method for the analysis of the formulated rutin ester was developed and validated. Moreover, the formulated ointment of decaacetylated rutin in our research laboratory was found to be stable under stability accelerated conditions. Synthesis of potentially more lipophilic compounds would yield novel rutin prodrugs suitable for topical formulation. Conclusion: This project provides a synthetic approach for many similar natural products. The research idea and strategy followed in this research project could be adapted by pharmaceutical and herbal establishments.

Formulation development & Evaluation of Phospholipids Complex of Euphorbia neriifolia Linn Extract

Phytoconstituents have been utilized as medicines for thousands of years, yet their application is limited owing to major hurdles like deficit lipid solubility, large molecular size and degradation in the gastric environment of gut. To overcome this hurdle, Novel Drug Delivery System (NDDS) proves to be a promising method for formulations containing phytoconstituents. In present work, phyto-phospholipids complex (phytosomes) of Euphorbia neriifolia L. has been prepared to improve the absorption and bioavailability of phytoconstituents. Euphorbia neriifolia L. consists of flavonoids, saponins and polyphenols which possess various medicinal properties. These constituents are hydrophilic in nature and have large molecular size, thus causing poor absorption. Phyto-phospholipids complex of Euphorbia neriifoliahas been prepared by taking Phosphatidylcholine (PC), Cholesterol and Euphorbia neriifolia extract in different ratio and the formulation been optimized to achieve maximum entrapment efficiency and smaller molecular size. The prepared phytosomes has been evaluated by Optical Microscopy, Transmission Electron Microscopy, Dynamic Light Scattering and UV/Vis Spectroscopy for physical appearance, entrapment efficiency, particle size, zeta potential and dissolution rate. The result so obtained indicates the improvement in the absorption rate and bioavailability of the phytoconstituents. Thus, Novel Drug Delivery System (NDDS) possess a great potential in overcoming the challenges of plant based formulations. Keywords: Euphorbia neriifolia, Phyto-phospholipids Complex, Novel Drug Delivery System, Phytosomes

A Case of High Dose Metoprolol Poisoning; Case Report and Literature Review

β-Blockers are prescribed by physicians for many medical reasons (hypertension, long-term prophylaxis of angina pectoris, myocardial infarction, stable heart failure treatment, cardiac arrhythmias, etc.). Although cases of β-blocker poisoning have a low rate of 0.9% among all poisoning cases, they have a high mortality rate. In β-blocker poisoning with high lipid solubility; seizures, respiratory depression, coma, resistant bradycardia-hypotension and shock may occur. Metoprolol, a type of β-blocker, is a selective β1-adrenoceptor antagonist with sympathomimetic effect. It is also reported that metoprolol is the 2nd most commonly prescribed β-blocker after bisoprolol all over the world. This article aims to present a case who took high-dose metoprolol for suicidal purposes and to examine metoprolol poisoning and its treatment in the light of current literature.

Gastrointestinal tract and skin permeability of chemicals in consumer products using parallel artificial membrane permeability assay (PAMPA)

Some chemicals commonly used in personal care products, household items, food vessels, cosmetics, and other consumer products are potentially harmful, and several reviews of epidemiological studies have suggested the associations between the chemical exposure from consumer products, and respiratory diseases, skin sensitization, and reproductive problems. Therefore, risk assessment is essential for management of consumer products safety. Necessarily, the estimation of human exposure is an essential step in risk assessment, and the absorption rate of those chemicals via the gastrointestinal tract, respiratory tract, and skin are very critical in determining the internal dose of the exposed chemicals. In this study, parallel artificial membrane permeability assays (PAMPA) for the gastrointestinal tract and skin were performed to evaluate the permeability of parabens (4-hydroxybenzoic acid, methyl-, propyl-, and butyl paraben), bisphenols (bisphenol A, bisphenol F, and bisphenol S), isothiazolinones (methyl-, chloromethyl-, benz-, octyl-, and dichlorooctyl isothiazolinone), and phthalates [diethyl-, dibutyl-, Di-isononyl-, and bis(2-ethylhexyl) phthalate]. Lipid solubility of test chemicals indicated by log P values was shown as the most critical factor and showed a positive association with the permeability of parabens, bisphenols, and isothiazolinones in PAMPA assay. However, phthalate showed a reverse-association between lipophilicity and permeability. The permeability of all the tested chemicals was higher in the gastrointestinal tract membrane than in the skin membrane. The pH in donor solution did not show significant effects on the permeability in all the chemicals, except the chemicals with a free hydrophilic moiety in their chemical structures.

β-adrenoceptor antagonists and nightmares: A pharmacoepidemiological–pharmacodynamic study

Aim: To compare different β-adrenoceptor antagonists for the risk of reporting nightmare. Methods: The study involved two approaches: first, we investigated in VigiBase®, the World Health Organization Individual Case Safety Report (ICSR) database, the disproportionality between exposure to each β-adrenoceptor antagonists and reports of nightmares between 1967 and 2019. Second, in a pharmacoepidemiological–pharmacodynamic analysis, we assessed whether use of β-adrenoceptor antagonists with moderate and high lipid solubility or strong 5-HT1A affinity were associated with an increased risk of reporting nightmares. We conducted multivariate logistic regression to estimate reporting odds ratios (RORs) of nightmares compared to all other adverse drug reactions. Results: Of the 126,964 reports recorded with β-adrenoceptor antagonists, 1138 (0.9%) were nightmares. The highest risk of reporting a nightmare was found with exposure of pindolol (adjusted ROR 2.82, 95%CI, 2.19–3.61), metoprolol (1.89, 1.66–2.16), and alprenolol (1.77, 1.06–2.97). Compared to use of low lipid solubility β-adrenoceptor antagonists, use of moderate or high lipid solubility β-adrenoceptor antagonists were significantly more associated with nightmare reports (aROR moderate vs. low 1.72, 95%CI 1.47–2.00 and aROR high vs. low 1.84, 95%CI 1.53–2.22). Use of moderate or high 5-HT1A affinity of β-adrenoceptor antagonists was associated with an increased ROR of nightmares compared with low 5-HT1A affinity of β-adrenoceptor antagonists (aROR moderate vs. low 1.22, 95%CI 1.04–1.43 and aROR high vs. low 2.46, 95%CI 1.93–3.13). Conclusion: In our large pharmacovigilance study, nightmares are more frequently reported for pindolol and metoprolol, and among β-adrenoceptor antagonists with high lipid solubility and high 5-HT1A receptor affinity.

Inhalant Abuse of Ethyl Chloride Spray: A Case Report

Ethyl chloride spray, which is usually used to relieve pain after injuries, is increasingly being used as a sniffing alternative. The number of people using this is rising due to its easy availability, cost-effectiveness and legality. The high lipid solubility of ethyl chloride leads to a rapid absorption of it in the lungs. However, data on the biotransformation of ethyl chloride in humans are sparse. We present the case of a 53-year-old male who had been inhaling ethyl chloride up to 3 times a week since 25 years, and describe his symptoms and the circumstances of abuse. This should help raise awareness of this issue so that abuse can be recognized early and rapid action taken.

Novel Facet of an Old Dietary Molecule? Direct Influence of Caffeine on Glucose and Biogenic Amine Handling by Human Adipocytes

Caffeine is a plant alkaloid present in food and beverages consumed worldwide. It has high lipid solubility with recognized actions in the central nervous system and in peripheral tissues, notably the adipose depots. However, the literature is scant regarding caffeine’s influence on adipocyte functions other than lipolysis, such as glucose incorporation into lipids (lipogenesis) and amine oxidation. The objective of this study was to explore the direct effects of caffeine and of isobutylmethylxanthine (IBMX) on these adipocyte functions. Glucose transport into fat cells freshly isolated from mice, rats, or humans was monitored by determining [3H]-2-deoxyglucose (2-DG) uptake, while the incorporation of radiolabeled glucose into cell lipids was used as an index of lipogenic activity. Oxidation of benzylamine by primary amine oxidase (PrAO) was inhibited by increasing doses of caffeine in human adipose tissue preparations with an inhibition constant (Ki) in the millimolar range. Caffeine inhibited basal and insulin-stimulated glucose transport as well as lipogenesis in rodent adipose cells. The antilipogenic action of caffeine was also observed in adipocytes from mice genetically invalidated for PrAO activity, indicating that PrAO activity was not required for lipogenesis inhibition. These caffeine inhibitory properties were extended to human adipocytes: relative to basal 2-DG uptake, set at 1.0 ± 0.2 for 6 individuals, 0.1 mM caffeine tended to reduce uptake to 0.83 ± 0.08. Insulin increased uptake by 3.86 ± 1.11 fold when tested alone at 100 nM, and by 3.21 ± 0.80 when combined with caffeine. Our results reinforce the recommendation of caffeine’s potential in the treatment or prevention of obesity complications.

Herbal Liposomes: Natural Network for Targeted Drug Delivery System

Herbal medicines have tremendous therapeutic potential that can explored across various effective drug delivery system. Decoctions, herbal teas, tinctures, glyceritum, oxymel, and use much soap, herbal tablets, herbal capsules, and herbal cream, herbal books, and prepared the confection of the most commonly available forms of dosage. The less use of herbal formulations in recent decades due to their lack of standardization. It is possible to use plant extract and isolated constituents to overcome this problem. But these phytoconstituents are suffering from drawbacks, mostly due to problems with stability and low lipid solubility. Novel drug delivery such as liposomes plays an important role in problem solving. Infact, compliance with the patient also improves. The review article discusses the recent status of new herbal liposomal formulations and describes the different ways in which these formulations are prepared.