Development and Optimization of Supercritical Fluid Extraction Setup Leading to Quantification of 11 Cannabinoids Derived from Medicinal Cannabis.

In this study, the optimal setup of supercritical fluid extraction (SFE) was designed and developed, leading to the quantitation of 11 distinct cannabinoids (cannabidivann (CBDV), tetrahydrocannabivann (THCV), cannabidiol (CBD), cannabigerol (CBG) cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabinol (CBN), delta 9-tetrahydrocannabinol (Δ9-THC), delta 8-tetrahydrocannabinol (Δ8-THC), cannabichomere (CBC) and delta 9-tetrahydrocannabinol acid (THCA-A)) extracted from the flowers of medicinal cannabis (sp. Sativa). Supercritical carbon dioxide (scCO2) extraction was performed at 37 °C, a pressure of 250 bar with the maximum theoretical density of CO2 (893.7 kg/m3), which generated the highest yield of cannabinoids from the flower-derived extract. Additionally, a cold separator (separating chamber) was used and positioned immediately after the sample containing chamber to maximize the yield. It was also found that successive washing of the extract with fresh scCO2 further increased yields. Ultra-high performance liquid chromatography coupled with DAD (uHPLC-DAD) was used to develop a method for the quantification of 11 cannabinoids. The C18 stationary phase was used in conjunction with a two solvent system gradient program resulting in the acquisition of the well-resolved chromatogram over a timespan of 32 min. The accuracy and precision of isolated cannabinoids across inter-and intra-day periods were within acceptable limits (<±15%). The assay was also fully validated and deemed sensitive from linearity, LOQ, and LOD perspective. The findings of this body of work are expected to facilitate improved conditions for the optimal extraction of select cannabinoids using scCO2, which holds promise in the development of well-characterized medicinal cannabis formulations. As to our best knowledge, this is the first study to report the uHPLC quantification method for the analysis of 11 cannabinoids from scCO2 extract in a single run with more than 1 min peak separation.

Are Medication Swallowing Lubricants Suitable for Use in Dysphagia? Consistency, Viscosity, Texture, and Application of the International Dysphagia Diet Standardization Initiative (IDDSI) Framework.

Medication lubricants are thick liquids or gels that are designed to aid swallowing of solid oral dosage forms. Tablets and capsules are placed within a spoonful of the product for swallowing. The aim of this study was to describe and compare commercially available medication lubricants in terms of textural suitability for patients with dysphagia. Twelve medication lubricants were characterised according to the International Dysphagia Diet Standardisation Initiative (IDDSI) framework. Apparent viscosity, yield stress, thickness consistency, and various texture features were compared. Gloup Forte was the only medication lubricant classified as IDDSI level 4 (pureed/extremely thick) at room (24 °C) temperature. Four other Gloup products were IDDSI level 3 (liquidised/moderately thick) at room temperature but testing at 4 °C or pouring from the container instead of using the pump dispenser resulted in classification as IDDSI level 4. The IDDSI Flow test would have classified MediSpend and Slo Tablets as IDDSI level 3, but their very low yield stress led to these fluids flowing too quickly through the prongs of a fork and so these were classified as <3. Severo was IDDSI level 2. Heyaxon and the two versions of Magic Jelly tested contained lumps, and Swallow Aid had exceptionally high viscosity, hardness, adhesiveness, and gumminess, classifying them as IDDSI Level 7 ("regular textures") and therefore as unsuitable for people with dysphagia according to IDDSI. This study provides valuable information to help with the selection of a safe medication lubricant with appropriate thickness level suited to each individual with dysphagia.

Nuts, cereals, seeds and legumes proteins derived emulsifiers as a source of plant protein beverages: A review.

Milk beverages derived from plant-based protein have attracted the interest of consumers and researchers as a health-promoting functional food. It can also be considered as a substitute for animal milk due to various allergy concerns associated with dairy milk. The plant-based emulsions are directed to prevent diet-related chronic diseases including diabetes, cardiovascular, obesity and other disorders due to the presence of healthy long-chain unsaturated fatty acids as compared to bovine milk. Further, associations between nutritional contents (vitamins, minerals and low fat) and pharmacological properties of plant-based protein may have extra beneficial effects. The review aims to summarize the four different groups of plant sources (nuts, cereals, seeds and legumes) used for the preparation of plant-based milk beverages. In addition, it also provides a detailed review of the general characteristics and functional properties of these plant sources. Physicochemical composition, protein and fats quality, functional properties, effect of heat and high-pressure treatment is also provided in detail. It also covers fats digestibility, protein stability, protein solubility and digestibility. Furthermore, the effect of processing, possible comparative study and potential applications in healthcare have been discussed.

Drug loss while crushing tablets: Comparison of 24 tablet crushing devices.

This study investigated 24 tablet crushing devices for drug loss using different methods to recover the crushed tablet. 24 devices were compared: 3 with disposable cups, 6 with disposable bags, 12 without separate vessels and 3 types of mortar and pestle. One paracetamol tablet was crushed and recovered by tapping the powder out. Where appropriate, depending on crusher size and manufacturer instructions, the powder was also recovered by mixing with water or food. Paracetamol recovery (quantity that can be delivered to a patient) and leftover (quantity remaining in the device) were measured using a validated UV method and the entire experiment was replicated 3 times. Drug recovery ranged from 86.7-98.1% when the crushed tablet was tapped out of the crushers (average loss 5.8%). Significant losses were measured for 18 crushers, particularly manually operated hand-twist crushers with a serrated crushing surface, and some devices with disposable bags or cups. Rinsing the crushed powder with water once resulted in an average of 24.2% drug loss, and this was reduced to 4.2% after a second rinse. If crushing is unavoidable, maximizing medication delivery to the patient is essential. Rinsing twice resulted in similar paracetamol recovery to tapping the powder out; however only water rinses have the potential for direct consumption by the patient, minimizing drug loss across the entire crushing and transfer process.

Oral medication delivery in impaired swallowing: thickening liquid medications for safe swallowing alters dissolution characteristics.

Acetaminophen (paracetamol) is available in a wide range of oral formulations designed to meet the needs of the population across the age-spectrum, but for people with impaired swallowing, i.e. dysphagia, both solid and liquid medications can be difficult to swallow without modification. The effect of a commercial polysaccharide thickener, designed to be added to fluids to promote safe swallowing by dysphagic patients, on rheology and acetaminophen dissolution was tested using crushed immediate-release tablets in water, effervescent tablets in water, elixir and suspension. The inclusion of the thickener, comprised of xanthan gum and maltodextrin, had a considerable impact on dissolution; acetaminophen release from modified medications reached 12-50% in 30 min, which did not reflect the pharmacopeia specification for immediate release preparations. Flow curves reflect the high zero-shear viscosity and the apparent yield stress of the thickened products. The weak gel nature, in combination with high G' values compared to G'' (viscoelasticity) and high apparent yield stress, impact drug release. The restriction on drug release from these formulations is not influenced by the theoretical state of the drug (dissolved or dispersed), and the approach typically used in clinical practice (mixing crushed tablets into pre-prepared thickened fluid) cannot be improved by altering the order of incorporation or mixing method.

Crushed tablets: does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release?

PURPOSE: To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. METHODS: Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. RESULTS: Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. CONCLUSIONS: Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted.

Validez del métddo extendido de hildebrand en l predicción de las solubilidadees de ibuprofén y naproxén en mezclas propilenoglicol + etanol / Valdity of the eextnded hildebrand solubility approach in the estiimation of ibuprofen and naproxen solubilities in propylene glycol + ethanol mixtures / Validez da aroxiimação ampliada da solubilidde de hildebrand na estimação dda solubilidade de ibuprofen e de naproxen em misturas do propileno glicol + etanol

En la presente investigación, el Método Extendido de Solubilidad de Hildebrand (MESH), desarrollado por Martin y cols . se ha aplicado al estudio de la solubilidad del ibuprofén (IBP) y del naproxén (NAP) en mezclas binarias propilenoglicol + etanol a 298,15 K ± 0,05 K. Se han utilizado los volúmenes molares aparentes de los solutos y las fracciones volumétricas de los solvente en las respectivas soluciones saturadas. Se encontró una adecuada capacidad predictiva del MESH al utilizar modelos polinómicos regulares de cuarto orden para IBP y de tercer orden para NAP, relacionando el parámetro de interacción W con el parámetro de solubilidad de las mezclas solventes. Sin embargo, las desviaciones obtenidas en la solubilidad estimada, respecto a los valores experimentales, fueron de magnitud semejante a las obtenidas al calcular esta propiedad directamente, utilizando regresiones empíricas de la solubilidad experimental de los fármacos en función del parámetro de solubilidad de las mezclas cosolventes.

In this work the Extended Hildebrand Solubility Approach (EHSA) developed by Martin et al ., has been applied to evaluate the solubility of ibuprofen (IBP) and naproxen (NAP) in propylene glycol + ethanol cosolvent mixtures at 298.15 K ± 0.05 K. Apparent molar volumes of the solutes and the volumetric fraction of the solvents in the saturated solutions were employed. A good predictive capacity of EHSA was found using regular polynomial models of order four for IBP and of order three for NAP, when the W interaction parameter was related to the solubility parameter of the solvent mixtures. Nevertheless, the deviations obtained for the estimated solubility respect to experimental solubility were of the same order as compared with those obtained directly using empiric regressions of the experimental solubilities as a function of the cosolvent solubility parameters.

Neste trabalho a aproximação ampliada da solubilidade de Hildebrand (AASH) desenvolvida por Martin e colaboradores, foi aplicada para avaliar a solubilidade de ibuprofeno e naproxeno em misturas cosolvente do propileno glicol + etanol do 298,15 K ± 0.05 K. Os volumes molares aparentes dos solutos e a fração volumétrica dos solventes nas soluções saturadas foram empregados. Uma boa capacidade predictiva de AASH foi encontrada do usar um modelo polinomial regular em ordem quatro para IBP e em ordem três para a NAP, quando o parâmetro da interação W foi relacionado ao parâmetro da solubilidade das misturas dos solventes. Não obstante, os desvios obtidos na solubilidade estimada respeito aos valores experimentais foram na mesma ordem comparada com as aquelas obtidas diretamente usando regressões empíricas das solubilidades experimentais em função dos parâmetros da solubilidade dos cosolventes.