Medication self-management capacity among older adults living in low-income housing communities.

BACKGROUND: Medication self-management capacity (MMC) is essential to safe and independent living. There is a need to understand the challenges low-income older adults face during the routine use of medications to promote safe medication use and healthy aging in place. OBJECTIVE: To assess the cognitive and physical deficiencies in MMC and the impact of using pharmaceutical aids/services on MMC among low-income older adults. METHODS: This was a cross-sectional study of 107 older residents of 5 low-income housing buildings in Richmond, VA. The Medication Management Instrument for Deficiencies in the Elderly was used to measure MMC during individual in-person interviews. Participants were asked whether they used any medication aids, including medication lists, organizers, or reminders, or pharmacy services such as specialized medication packaging, medication synchronization, prescription home delivery, or mail order services. Multiple regression modeling was used to assess the relationship between MMC and the use of pharmaceutical aids/services. RESULTS: Eighty-nine percent of participants were African American with a mean (standard deviation [±SD]) age of 68.5 (7.2) years. The mean deficit in MMC was 3 (±2.0). The most challenging skill was naming all the medications (69.2%), followed by stating their indications (46.7%) and knowing how or when all of the medications should be taken (38.3%). Seventy-nine percent used at least 1 pharmaceutical aid/service; using 1 pharmaceutical aid/service was significantly associated with better MMC (P = .0285). Low educational level and health literacy were associated with deficits in MMC (P < .05). CONCLUSION: Many older adults residing in low-income housing had impaired capacity to manage their medications independently. Inadequate medication knowledge affected their cognitive ability to manage medications. Using a pharmaceutical aid/service was associated with better MMC. Greater attention to developing medication self-management skills for older adults with low health literacy and adverse social determinants of health is needed.

Revisión de medicamentos sin receta con aspartamo: Indicación Farmacéutica segura en fenilcetonuria / Review of non-prescription medicines with aspartame: safe pharmaceutical indication in phenylketonuria

Introducción: La fenilcetonuria es el trastorno hereditario más frecuente del metabolismo de los aminoácidos y su abordaje suele centrarse en die-tas restringidas en fenilalanina, un aminoácido presente en el edulcorante aspartamo habitualmente usado como excipiente en tecnología farmacéutica. Objetivo: El objetivo principal es la revisión de los medicamentos sin receta comercializados en España hasta marzo de 2023 y que contienen aspartamo en su composición. Método: Se realizó una revisión en la base de datos BOT plus de todos los medicamentos comercializados en España que contienen aspartamo. Se seleccionaron solo los MSR. Se consultaron las fichas técnicas en el Centro de información online de medicamentos de la AEMPS (CIMA), y los datos obtenidos se registraron en una tabla. Resultados: Se obtuvieron 570 medicamentos; 58 eran MSR. Cuando exista petición de MSR con aspartamo en pacientes con fenilcetonuria, en el SIF, tras su evaluación, en el 100% de los casos, el farmacéutico aplicando el Servicio de Indicación Farmacéutica podría indicar un MSR alternativo, con el mismo principio activo pero sin aspartamo como excipiente. Conclusiones: La actuación del farmacéutico comunitario para aplicar el SIF es muy importante en pacientes con fenilcetonuria. Existen medicamentos que no requieren prescripción y se pueden indicar en estos pacientes. El farmacéutico debe tener a su disposición las herramientas necesarias que le faciliten el SIF con este tipo de enfermos. (AU)

Introduction: Phenylketonuria is the most common inherited disorder of amino acid metabolism and its management usually focuses on diets restricted in phenylalanine, an amino acid present in the sweet-ener aspartame commonly used as an excipient in pharmaceutical technology. Objective: The main objective is the review of non-prescription medicines marketed in Spain until March 2023 and that contain aspartame in their composition.Methods: A review of all medicines marketed in Spain containing aspartame was carried out in the BOT plus database. Only MSRs were selected. The data sheets were consulted at the AEMPS online medicines information centre (CIMA), and the data obtained were recorded in a table.Results: 570 medicines were obtained; 58 were MSRs. When there is a request for MSRs with aspartame in patients with phenylketonuria, in the SIF, after evaluation, in 100% of the cases, the pharmacist applying the Pharmaceutical Indication Service could indicate an alternative MSR, with the same active ingredient but without aspartame as an excipient.Conclusions: The action of the community phar-macist to apply the SIF is very important in patients with phenylketonuria. There are medicines that do not require a prescription and can be prescribed for these patients. Pharmacists should have the necessary tools at their disposal to facilitate the SIF with this type of patient. (AU)

Medicamentos y productos sanitarios inteligentes: ¿Oportunidad o quimera? / Smart medicines and medical devices: Opportunity or chimera?

Los medicamentos y los productos sanitarios capaces de controlar la cesión de fármacos y sustancias activas en respuesta a estímulos pueden mejorar significativamente la eficacia terapéutica de los tratamientos y abren nuevas posibilidades para avanzar en el campo de la medicina personalizada. Los sistemas sensibles a estímulos hacen posible la liberación precisa de sustancias activas en el lugar y el momento adecuados y a la velocidad más conveniente utilizando dosis más reducidas que las que se requieren usando estrategias convencionales. Los avances en este campo están directamente ligados a la evolución de la ciencia de los materiales, que hace posible disponer de biomateriales y excipientes no sólo bioactivos sino también moduladores de la respuesta biológica. Los sistemas de liberación controlada modulados por activación y regulados por retroalimentación, basados en aproximaciones bioinspiradas, ya han demostrado su potencial en las fases preclínicas. La utilización con éxito en clínica de algunos de ellos es un estímulo para seguir avanzando en este campo. (AU)

Medicines and medical devices capable of controlling the release of drugs and active substances in response to stimuli can significantly improve the therapeutic efficacy of treatments already implemented and open up new possibilities for advancing in the field of personalized medicine. Stimulus-responsive systems enable precise delivery of active substances at the right place and time and at the most convenient rate using lower doses than are required using conventional strategies. Advances in this field are directly linked to the evolution of materials science that makes it possible to have biomaterials and excipients that are not only bioactive but also modulators of the biological response. Activation-modulated and feedback-regulated controlled-release systems, based on bioinspired approaches, have already demonstrated their potential in the preclinical phases. The successful clinical use of some of them is an encouragement to continue advancing in this field. (AU)

Control de carbohidratos en los medicamentos antiepilépticos para niños con dieta cetogénica / Controlling carbohydrate content in antiepileptic medications for children on a ketogenic diet

Introducción: los pacientes que siguen una dieta cetogénica para el control de las crisis epilépticas deben llevar a cabo un estricto control de los hidratos de carbono procedentes tanto de los alimentos que consumen como de los medicamentos que tienen pautados. Tanto en la instauración de la dieta cetogénica como cuando el médico prescribe un medicamento nuevo es necesario el ajuste de la medicación a las formas farmacéuticas más adecuadas, de forma que se minimice el aporte de excipientes en forma de hidratos de carbono de los medicamentos.Objetivos:el objetivo que planteamos en el presente trabajo fue elaborar un listado de medicamentos antiepilépticos de utilización habitual en neurología pediátrica que incluyera información sobre su contenido calórico en forma de hidratos de carbono para la administración a pacientes con dieta cetogénica.Métodos:en cada medicamento incluido en el listado se revisó el contenido en excipientes considerados hidratos de carbono y derivados que pudieran influir en la cetosis del paciente. Se calculó el contenido calórico procedente de los hidratos de carbono y polioles de cada medicamento.Resultados:elaboración de una tabla para consulta del contenido calórico de distintos medicamentos antiepilépticos utilizados en neurología pediátrica para pacientes con dieta cetogénica.Conclusiones:la tabla publicada pretende ser una herramienta útil que permita la consulta del contenido calórico de distintos medicamentos antiepilépticos y la selección del medicamento idóneo que menos afecte a la dieta cetogénica. Con el contenido calórico en carbohidratos de las medicaciones pautadas se podrán realizar los ajustes necesarios en la dieta para mantener la cetosis necesaria. (AU)

Introduction: patients who follow a ketogenic diet for the control of epileptic seizures must carry out a strict control of carbohydrates from the foods they eat and the medicines they are prescribed. In the initiation of a ketogenic diet and when a doctor prescribes a new medication, it is necessary to select the most appropriate pharmaceutical form so that the supply of excipients in the form of carbohydrates from the drugs is minimized.Objectives:the goal of the present paper was to compile a list of carbohydrate and caloric contents in antiepileptic drugs commonly used in pediatric neurology.Methods:in each medication included in the list, the content of excipients considered carbohydrates and derivatives that could influence the patient's ketosis was reviewed. The caloric content from carbohydrates and polyols in each medication was calculated.Results:the table provides the total carbohydrate and caloric content for antiepileptic medications in pediatric patients consuming the ketogenic diet.Conclusions:this table is intended to be a useful tool to help clinicians select a pharmaceutical form that is less likely to affect the ketogenic diet. Additionally, knowing the carbohydrate content of a new medication will allow adjustment of the diet to maintain ketosis. (AU)

Formulation development of directly compressible mebevarine tablets using superdisintegrant: A way to investigate quality atributes, in vitro release kinetics and stability profile.

In order for preparing a solid oral dosage form, tablet quality is of significant concern. Compressibility behavior of different powders and mixtures of formulations and release pattern of any tablets are characteristic measures to define prerequisite quality attributes of any compressed formulations. There are basically two major methods that can be adopted for the preparation of tablets including granulation and direct compression. Later process offer fewer processing steps and agreeable release profile with acceptable quality parameters and hence preferred over granulation method. In this investigation Mebeverine hydrochloride an anti-muscarinic drug is studied for compression and release behavior using various concentrations of filler binders and disintegrants via rotatable central composite design (CCRD) option of design expert (software). Nine formulations were developed from F1 to F9 with Crospovidone (superdisintegrant) as (X1) (-α=1.17% to ± α=6.83%) and microcrystalline cellulose (Avicel 102, Filler/binder) as X2 (-α = 29.82% to ± α = 65.18%). Disintegration Time (DT) as (R1) and Hardness in (kg) as (R2) were determined as two dependent response variables. The performance of powder blends and formulations was analyzed by micromeritic and physico-chemical and assessments. Dissolution comparisons were statistically analyzed by ANOVA and model dependent and in-dependent methods. Best fit model was found to be Hixon-crowell's model (r2 = 0.995) followed by Weibull's model (r2 = 0.985). The Trial formulations F2, F4, F6 and F8 were also studied on accelerated conditions (40±5ºC 75%±5% RH) for stability tests and validity of the formulations in months were also determined between 35-39 months.

Application of armodafinil-loaded microneedle patches against the negative influence induced by sleep deprivation.

Cognition maintenance is essential for healthy and safe life if sleep deprivation happens. Armodafinil is a wake-promoting agent against sleep deprivation related disorders. However, only the tablet formulation is available, which may limit its potential in some circumstances. Here, we report the synthesis of a new formulation of armodafinil, microneedle patches, which can be conveniently used by any individual and removed in time if not wanted. To produce the needles of higher mechanical strength and higher drug loading, polyvinylpyrrolidone (PVP) K90 was used to fabricate armodafinil-loaded microneedles by applying the mold casting method after dissolving in methanol and drying. The higher mechanical strength was validated by COMSOL Multiphysics® software stimulation and universal mechanical testing machines. The obtained armodafinil microneedles can withstand a force of 70 N and penetrate the skin to a depth of 230 µm, and quickly released the drug within 1.5 h in vitro. The pharmacokinetic analysis showed that microneedle administration can maintain a more lasting and stable blood concentration as compared to oral administration. After the treatment of sleep deprived mice with microneedles, the in vivo pharmacodynamics study clearly demonstrated that armodafinil microneedles could eliminate the effects of sleep deprivation and improve the cognitive functions of sleep-deprived mice. A self-administered, high drug-loaded microneedle patch were prepared successfully, which appeared to be highly promising in preserving cognition by transdermal administration.

Formulation strategies to improve the efficacy of intestinal permeation enhancers.

The use of chemical permeation enhancers (PEs) is the most widely tested approach to improve oral absorption of low permeability active agents, as represented by peptides. Several hundred PEs increase intestinal permeability in preclinical bioassays, yet few have progressed to clinical testing and, of those, only incremental increases in oral bioavailability (BA) have been observed. Still, average BA values of ~1% were sufficient for two recent FDA approvals of semaglutide and octreotide oral formulations. PEs are typically screened in static in vitro and ex-vivo models where co-presentation of active agent and PE in high concentrations allows the PE to alter barrier integrity with sufficient contact time to promote flux across the intestinal epithelium. The capacity to maintain high concentrations of co-presented agents at the epithelium is not reached by standard oral dosage forms in the upper GI tract in vivo due to dilution, interference from luminal components, fast intestinal transit, and possible absorption of the PE per se. The PE-based formulations that have been assessed in clinical trials in either immediate-release or enteric-coated solid dosage forms produce low and variable oral BA due to these uncontrollable physiological factors. For PEs to appreciably increase intestinal permeability from oral dosage forms in vivo, strategies must facilitate co-presentation of PE and active agent at the epithelium for a sustained period at the required concentrations. Focusing on peptides as examples of a macromolecule class, we review physiological impediments to optimal luminal presentation, discuss the efficacy of current PE-based oral dosage forms, and suggest strategies that might be used to improve them.

Influence of Plasdone™ S630 Ultra-an Improved Copovidone on the Processability and Oxidative Degradation of Quetiapine Fumarate Amorphous Solid Dispersions Prepared via Hot-Melt Extrusion Technique.

In a formulation, traces of peroxides in copovidone can impact the stability of drug substances that are prone to oxidation. The present study aimed to investigate the impact of peroxides in novel Plasdone™ S630 Ultra and compare it with regular Plasdone™ S630 on the oxidative degradation of quetiapine fumarate amorphous solid dispersions prepared via hot-melt extrusion technique. The miscibility of copovidones with drug was determined using the Hansen solubility parameter, and the results indicated a miscible drug-polymer system. Melt viscosity as a function of temperature was determined for the drug-polymer physical mixture to identify the suitable hot-melt extrusion processing temperature. The binary drug and polymer (30:70 weight ratio) amorphous solid dispersions were prepared at a processing temperature of 160°C. Differential scanning calorimetry and Fourier transform infrared spectroscopy studies of amorphous solid dispersions revealed the formation of a single-phase amorphous system with intermolecular hydrogen bonding between the drug and polymer. The milled extrudates were compressed into tablets by using extragranular components and evaluated for tabletability. Stability studies of the milled extrudates and tablet formulations were performed to monitor the oxidative degradation impurity (N-oxide). The N-oxide impurity levels in the quetiapine fumarate - Plasdone™ S630 Ultra milled extrudates and tablet formulations were reduced by 2- and 3-folds, respectively, compared to those in quetiapine fumarate - Plasdone™ S630. The reduced oxidative degradation and improved hot-melt extrusion processability of Plasdone™ S630 Ultra make it a better choice for oxidation-labile drugs over Plasdone™ S630 copovidone.

Evaluation of the Stability of Bacteriophages in Different Solutions Suitable for the Production of Magistral Preparations in Belgium.

In Belgium, the incorporation of phages into magistral preparations for human application has been permitted since 2018. The stability of such preparations is of high importance to guarantee quality and efficacy throughout treatments. We evaluated the ability to preserve infectivity of four different phages active against three different bacterial species in five different buffer and infusion solutions commonly used in medicine and biotechnological manufacturing processes, at two different concentrations (9 and 7 log pfu/mL), stored at 4 °C. DPBS without Ca2+ and Mg2+ was found to be the best option, compared to the other solutions. Suspensions with phage concentrations of 7 log pfu/mL were unsuited as their activity dropped below the effective therapeutic dose (6-9 log pfu/mL), even after one week of storage at 4 °C. Strong variability between phages was observed, with Acinetobacter baumannii phage Acibel004 being stable in four out of five different solutions. We also studied the long term storage of lyophilized staphylococcal phage ISP, and found that the titer could be preserved during a period of almost 8 years when sucrose and trehalose were used as stabilizers. After rehydration of the lyophilized ISP phage in saline, the phage solutions remained stable at 4 °C during a period of 126 days.

Immediate-Release Formulations Produced via Twin-Screw Melt Granulation: Systematic Evaluation of the Addition of Disintegrants.

The current study evaluated the effect of location and amount of various superdisintegrants on the properties of tablets made by twin-screw melt granulation (TSMG). Sodium-croscarmellose (CCS), crospovidone (CPV), and sodium starch glycolate (SSG) were used in various proportions intra- and extra-granular. Tabletability, compactibility, compressibility as well as friability, disintegration, and dissolution performance were assessed. The extra-granular addition resulted in the fasted disintegration and dissolution. CPV performed superior to CCS and SSG. Even if the solid fraction (SF) of the granules was lower for CPV, only a minor decrease in tabletability was observed, due to the high plastic deformation of the melt granules. The intra-granular addition of CPV resulted in a more prolonged dissolution profile, which could be correlated to a loss in porosity during tableting. The 100% intra-granular addition of the CPV resulted in a distinct decrease of the disintegration efficiency, whereas the performance of SSG was unaffected by the granulation process. CCS was not suitable to be used for the production of an immediate-release formulation, when added in total proportion into the granulation phase, but its efficiency was less impaired compared to CPV. Shortest disintegration (78 s) and dissolution (Q80: 4.2 min) was achieved with CPV extra-granular. Using CPV and CCS intra-granular resulted in increased disintegration time and Q80. However, at a higher level of appx. 500 s and appx. 15 min, only SSG showed a process and location independent disintegration and dissolution performance.

Neurobehavior and neuron damage following prolonged exposure of silver nanoparticles with/without polyvinylpyrrolidone coating in Caenorhabditis elegans.

Silver nanoparticles (AgNPs) have become widespread in the environment with increasing industrial applications. But the studies about their potential health risks are far from enough, especially in neurotoxic effects. This study aimed to investigate the neurotoxic effects of longer-term exposure (prolonged exposure for 48 h and chronic exposure for 6 days) of 20nm AgNPs with/without polyvinylpyrrolidone (PVP) coating at low concentrations (0.01-10 mg·L-1 ) to Caenorhabditis elegans. The results suggested that exposure to AgNPs induced damage to nematode survival, with the longest and relative average life span reduced. Exposure to AgNPs caused neurotoxicity on locomotion behaviors (head thrashes, body bends, pharyngeal pumping frequency, and defecation interval) and sensory perception behaviors (chemotaxis assay and thermotaxis assay), as well as impaired dopaminergic, GABAergic, and cholinergic neurons, except for glutamatergic, based on the alters fluorescence intensity, in a dose- and time-dependent manner. Further investigations suggested that the low-dose AgNPs (0.01-0.1 mg·L-1 ) exposure raises receptors of GABAergic and dopamine in C. elegans at the genetic level, whereas opposite results were observed at higher doses (1-10 mg·L-1 ), which implied that AgNPs could cause neurotoxicity by impairing neurotransmitter delivery. The PVP-AgNPs could cause a higher fatality rate and neurotoxicity at the same dose. Notably, AgNPs did not cause any deleterious effect on nematodes at the lowest dose of 0.01 mg·L-1 . In general, these results suggested that AgNPs possess the neurotoxic potential in C. elegans and provided useful information to understand the neurotoxicity of AgNPs, which would offer an inspiring perspective on the safe application.

Elucidating the Molecular Mechanism of Drug-Polymer Interplay in a Polymeric Supersaturated System of Rifaximin.

Supersaturated drug delivery system (SDDS) enables the solubility and sustained membrane transport of poorly water-soluble drugs. SDDS provides higher drug concentration in the dispersed phase and equilibrium in the continuous phase, which corresponds to amorphous solubility of the drug. Rifaximin (RFX) is a nonabsorbable BCS class IV drug approved for the treatment of irritable bowel syndrome and effective against Helicobacter pylori. RFX shows slow crystallization and precipitation in an acidic pH of 1.2-2, leading to obliteration of its activity in the gastrointestinal tract. The objective of the present study is to inhibit the precipitation of RFX, involving screening of polymers at different concentrations, using an in-house developed microarray plate method and solubility studies which set forth hydroxypropyl methylcellulose (HPMC) E15, Soluplus, and polyvinyl alcohol to be effective precipitation inhibitors (PIs). Drug-polymer precipitates (PPTS) are examined for surface morphology by scanning electron microscopy, solid-phase transformation by hot stage microscopy, the nature of PPTS by polarized light microscopy, and drug-polymer interactions by Fourier transform infrared and nuclear magnetic resonance spectroscopy. Besides, the unfathomed molecular mechanism of drug-polymer interplay is discerned at the air-water interface using sum-frequency generation spectroscopy to correlate the interfacial hydrogen bonding properties in bulk water. Surprisingly, all studies disseminate HPMC E15 and Soluplus as effective PIs of RFX.

[Ocular Drug Delivery System-based on Solid Nanoparticles].

The use of eye drops is a well-established practice in the treatment of ophthalmic diseases, although the bioavailability of traditional eye drops, which are either solutions or suspensions, is insufficient, as the corneal barrier and dilution by lacrimation prevent the transcorneal penetration of drugs. Additionally, frequent instillation may cause undesirable systemic side effects and local corneal toxicity. To overcome these problems, micro- and nanoparticles, hydrogels, and viscous solutions have been tested, and solid nanoparticles are also expected to be applied. This review examines the usefulness of ophthalmic formulations based on solid nanoparticles, by using the specific example of indomethacin (IMC). Ophthalmic formulations based on solid IMC nanoparticles (IMC-NP dispersions) have been prepared using various additives (benzalkonium chloride, mannitol, methylcellulose, and cyclodextrin) and a rotation/revolution pulverizer (NP-100), to produce particles of 50-220 nm in size. The solubility of IMC in IMC-NP dispersions was 4.18-fold higher than that in the suspensions containing IMC microparticles (IMC-MP suspensions), and IMC-NP dispersions were better tolerated than commercially available NSAIDs eye drops, such as IMC, pranoprofen, diclofenac, bromfenac, and nepafenac eyedrops, in human corneal epithelial cells. Moreover, the corneal penetration in IMC-NP dispersions was higher than that in commercially available IMC and IMC-MP suspensions, and three energy-dependent endocytosis pathways (clathrin-dependent endocytosis, caveolae-dependent endocytosis, and macropinocytosis) were related to the high ophthalmic bioavailability of IMC-NP dispersions. This information can be used to support future studies aimed at designing novel ophthalmic formulations.

A novel food-based foam as oral contrast agent with negative Hounsfield units for demarcation of small bowel loops on abdominal CT: tolerability and bowel distension in 25 volunteers.

BACKGROUND: Diseases of the bowel are not always displayed on conventional abdominal computed tomography (CT). The studied oral contrast agent aims to improve this. PURPOSE: To investigate whether the use of a novel oral contrast for abdominal CT enables the same diagnostic advantages as seen in magnetic resonance imaging (MRI). MATERIAL AND METHODS: Twenty-five consented volunteers drank up to 1400 mL of a stable, drinkable foam. Comments on acceptance and side effects were noted immediately and 24 h later. Foam palatability was documented through interviews, and distribution in the small bowel by Hounsfield units from the CT software. The CT results were compared with age- and sex-matched controls, pretreated according to routine. A non-enhanced abdominal CT protocol of lowest possible radiation dose was used. External referees evaluated all data obtained. RESULTS: Foam was considered odd to swallow, and fullness was reported by all volunteers after 950 mL. Five had difficulties in drinking the last 320 mL and two abstained from it. All adverse symptoms were mild. The distribution in the small bowel was on par with standard agents. Foam density revealed stability with intraluminal values of around -550 HU from stomach to terminal ileum, satisfying the requirement of a great bowel lumen-to-wall contrast. External reviewers re-evaluated all our data, and one predicted the foam to offer a potential for improved diagnostics. CONCLUSION: A CT true-negative bowel filling agent was formulated, with high acceptance, few side effects, and a potential to mimic T1-weighted MRI images.

A Patient With Bilateral Conjunctivitis Positive for SARS-CoV-2 RNA in a Conjunctival Sample.

PURPOSE: To present a patient with bilateral conjunctivitis, testing positive for viral RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in both nasopharyngeal and conjunctival samples. METHODS: A 40-year-old man with bilateral acute conjunctivitis and suspicious signs of coronavirus disease 2019 (COVID-19) presented to the hospital. A detailed ophthalmic examination was performed. Samples obtained from conjunctival and nasopharyngeal swabs were tested by reverse transcription PCR (RT-PCR) for the detection of SARS-CoV-2 virus. Ocular findings and duration of the presence of viral RNA in the conjunctival specimens were evaluated at follow-up visits. RESULTS: Slit-lamp biomicroscopy revealed bilateral acute follicular conjunctivitis. The RT-PCR assay demonstrated the presence of viral RNA in the nasopharyngeal and conjunctival specimens at the initial visit and at the 4-day follow-up. Conjunctivitis findings were decreased after 4 days and recovered completely without any sequelae within10 days. The PCR results of both nasopharyngeal and conjunctiva specimens were negative for the viral RNA at 10 days. CONCLUSIONS: Bilateral conjunctivitis is rare in patients infected with COVID-19. Although it is difficult to detect viral RNA from conjunctival swabs, conjunctival secretions may be a source of contamination, and protective measures must be taken.

Historical Evolution and Provider Awareness of Inactive Ingredients in Oral Medications.

PURPOSE: A multitude of different versions of the same medication with different inactive ingredients are currently available. It has not been quantified how this has evolved historically. Furthermore, it is unknown whether healthcare professionals consider the inactive ingredient portion when prescribing medications to patients. METHODS: We used data mining to track the number of available formulations for the same medication over time and correlate the number of available versions in 2019 to the number of manufacturers, the years since first approval, and the number of prescriptions. A focused survey among healthcare professionals was conducted to query their consideration of the inactive ingredient portion of a medication when writing prescriptions. RESULTS: The number of available versions of a single medication have dramatically increased in the last 40 years. The number of available, different versions of medications are largely determined by the number of manufacturers producing this medication. Healthcare providers commonly do not consider the inactive ingredient portion when prescribing a medication. CONCLUSIONS: A multitude of available versions of the same medications provides a potentially under-recognized opportunity to prescribe the most suitable formulation to a patient as a step towards personalized medicine and mitigate potential adverse events from inactive ingredients.

New Design Strategies for Controlling the Rate of Hydrophobic Drug Release from Nanoemulsions in Blood Circulation.

The intravenous administration of drug-loaded nanoparticles (NPs) is needed to achieve passive or active targeting in disease tissues. However, when the loaded drug is a hydrophobic small molecule, the NPs fail to reach adequate plasma drug concentrations mainly because of premature drug release. The pharmacokinetics of such drugs can be controlled by covalent modification, but this approach could compromise the safety or potency of the drug. In this study, we investigated two formulation parameters that could be used to improve the plasma concentrations of unmodified drugs that are loaded in a nanoemulsion (NE), a core-shell type NP. The first parameter is the loading ratio, and the second is the affinity of the drug to the core. Optimized NEs with reduced drug loading and with a high drug-core affinity resulted in a 12.4- and 11.2-fold increase in the plasma retention of curcumin and paclitaxel, respectively. Our strategy for enhancing the drug-core interaction affinity relied on mixing oils and surfactants to achieve cooperativity in noncovalent interactions, such as hydrophobic interactions, hydrogen bonding, and π-π stacking, which was further confirmed by theoretical calculations of interaction affinities. Finally, we report on the development of a cinnamic acid-derived oil-like material as a novel drug vehicle with exceptional solubilizing ability that could be used in intravenous formulations of NEs.

Effects of Coformer and Polymer on Particle Surface Solution-Mediated Phase Transformation of Cocrystals in Aqueous Media.

The purpose of the present study was to investigate the effect of the coformer difference on particle surface solution-mediated phase transformation (PS-SMPT) during cocrystal particle dissolution in aqueous media in the absence and presence of polymers. SMPT can occur either in the bulk phase or at the particle surface because drug molecules can be supersaturated at the dissolving cocrystal surface, as well as in the bulk phase. Previously, bulk phase SMPT has been primarily investigated in formulation development. However, little is known about the effects of coformers and polymers on PS-SMPT of cocrystals. In this study, six carbamazepine (CBZ) cocrystals were used as model cocrystals (malonic acid (MAL), succinic acid (SUC), glutaric acid (GLA), adipic acid (ADP), saccharin (SAC), and nicotinamide (NCT); nonsink dissolution tests were performed with or without a precipitation inhibitor (hydroxypropyl methylcellulose (HPMC)) at pH 6.5. The residual particles were analyzed by powder X-ray diffraction, differential scanning calorimetry, polarized light microscopy (PLM), and scanning electron microscopy. Real-time PLM was used to directly observe rapid PS-SMPT. In the absence of HPMC, supersaturation was not observed in the bulk phase for all cocrystals. All cocrystals rapidly transformed to CBZ dihydrate aggregates via PS-SMPT (mostly within 1 min). In contrast, in the presence of 0.1% HPMC, supersaturation was observed for CBZ-SUC, CBZ-ADP, CBZ-SAC, and CBZ-NCT but not for CBZ-MAL and CBZ-GLA. The cocrystals with lower solubility coformers tended to induce higher supersaturation in the bulk phase. The PS-SMPT of CBZ-SUC, CBZ-ADP, and CBZ-SAC was slowed down by HPMC. By suppressing PS-SMPT, the cocrystals exhibited its supersaturation potential, depending on the properties of each coformer. To take advantage of the supersaturation potential of cocrystals to improve oral drug absorption, it is important to suppress particle surface SMPT in addition to bulk phase SMPT.

Can adjuncts to bowel preparation for colonoscopy improve patient experience and result in superior bowel cleanliness? A systematic review and meta-analysis.

BACKGROUND: Bowel preparation for colonoscopy is often poorly tolerated due to poor palatability and adverse effects. This can negatively impact on the patient experience and on the quality of bowel preparation. This systematic review and meta-analysis was carried out to assess whether adjuncts to bowel preparation affected palatability, tolerability and quality of bowel preparation (bowel cleanliness). METHODS: A systematic search strategy was conducted on PubMed, MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews to identify studies evaluating adjunct use for colonoscopic bowel preparation. Studies comparing different regimens and volumes were excluded. Specific outcomes studied included palatability (taste), willingness to repeat bowel preparation, gastrointestinal adverse events and the quality of bowel preparation. Data across studies were pooled using a random-effects model and heterogeneity assessed using I2-statistics. RESULTS: Of 467 studies screened, six were included for analysis (all single-blind randomised trials; n = 1187 patients). Adjuncts comprised citrus reticulata peel, orange juice, menthol candy drops, simethicone, Coke Zero and sugar-free chewing gum. Overall, adjunct use was associated with improved palatability (mean difference 0.62, 95% confidence interval 0.29-0.96, p < 0.001) on a scale of 0-5, acceptability of taste (odds ratio 2.75, 95% confidence interval: 1.52-4.95, p < 0.001) and willingness to repeat bowel preparation (odds ratio 2.92, 95% confidence interval: 1.97-4.35, p < 0.001). Patients in the adjunct group reported lower rates of bloating (odds ratio 0.48, 95% confidence interval: 0.29-0.77, p = 0.003) and vomiting (odds ratio 0.47, 95% confidence interval 0.27-0.81, p = 0.007), but no difference in nausea (p = 0.10) or abdominal pain (p = 0.62). Adjunct use resulted in superior bowel cleanliness (odds ratio 2.52, 95% confidence interval: 1.31-4.85, p = 0.006). Heterogeneity varied across outcomes, ranging from 0% (vomiting) to 81% (palatability), without evidence of publication bias. The overall quality of evidence was rated moderate. CONCLUSION: In this meta-analysis, the use of adjuncts was associated with better palatability, less vomiting and bloating, willingness to repeat bowel preparation and superior quality of bowel preparation. The addition of adjuncts to bowel preparation may improve outcomes of colonoscopy and the overall patient experience.