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1.
J Am Pharm Assoc (2003) ; 64(1): 88-95, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38453663

RESUMEN

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.


Asunto(s)
Vivienda , Automanejo , Anciano , Humanos , Estudios Transversales , Vida Independiente , Excipientes Farmacéuticos , Preparaciones Farmacéuticas , Persona de Mediana Edad
2.
Eur J Pharm Biopharm ; 169: 178-188, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34700002

RESUMEN

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.


Asunto(s)
Cognición/efectos de los fármacos , Microtecnología/métodos , Modafinilo , Agujas , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Administración Cutánea , Animales , Cognición/fisiología , Sistemas de Liberación de Medicamentos/métodos , Monitoreo de Drogas/métodos , Ratones , Modafinilo/administración & dosificación , Modafinilo/farmacocinética , Excipientes Farmacéuticos/farmacología , Povidona/farmacología , Absorción Cutánea , Privación de Sueño , Trastornos del Sueño-Vigilia/psicología , Solubilidad , Parche Transdérmico , Promotores de la Vigilia/administración & dosificación , Promotores de la Vigilia/farmacocinética
3.
Pak J Pharm Sci ; 34(3): 915-924, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34602414

RESUMEN

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.


Asunto(s)
Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/farmacocinética , Fenetilaminas/administración & dosificación , Fenetilaminas/farmacocinética , Comprimidos , Celulosa , Química Farmacéutica , Liberación de Fármacos , Estabilidad de Medicamentos , Excipientes , Dureza , Técnicas In Vitro , Excipientes Farmacéuticos , Povidona
4.
Adv Drug Deliv Rev ; 177: 113925, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34418495

RESUMEN

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.


Asunto(s)
Composición de Medicamentos , Absorción Intestinal , Excipientes Farmacéuticos , Animales , Formas de Dosificación , Sistemas de Liberación de Medicamentos , Interacciones Alimento-Droga , Humanos , Permeabilidad , Excipientes Farmacéuticos/administración & dosificación , Excipientes Farmacéuticos/química , Excipientes Farmacéuticos/farmacocinética
5.
Viruses ; 13(5)2021 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-34066841

RESUMEN

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.


Asunto(s)
Bacteriófagos/fisiología , Excipientes Farmacéuticos , Soluciones , Bacterias/virología , Liofilización , Humanos , Excipientes Farmacéuticos/química , Temperatura
6.
AAPS PharmSciTech ; 22(5): 196, 2021 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-34184149

RESUMEN

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.


Asunto(s)
Tecnología de Extrusión de Fusión en Caliente/métodos , Excipientes Farmacéuticos/síntesis química , Povidona/síntesis química , Pirrolidinas/síntesis química , Fumarato de Quetiapina/síntesis química , Compuestos de Vinilo/síntesis química , Rastreo Diferencial de Calorimetría/métodos , Química Farmacéutica/métodos , Composición de Medicamentos/métodos , Calor , Oxidación-Reducción , Excipientes Farmacéuticos/farmacocinética , Povidona/farmacocinética , Pirrolidinas/farmacocinética , Fumarato de Quetiapina/farmacocinética , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Compuestos de Vinilo/farmacocinética
7.
AAPS PharmSciTech ; 22(5): 183, 2021 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-34132921

RESUMEN

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.


Asunto(s)
Carboximetilcelulosa de Sodio/síntesis química , Química Farmacéutica/métodos , Composición de Medicamentos/métodos , Povidona/síntesis química , Carboximetilcelulosa de Sodio/farmacocinética , Evaluación Preclínica de Medicamentos/métodos , Excipientes/síntesis química , Excipientes/farmacocinética , Excipientes Farmacéuticos/síntesis química , Excipientes Farmacéuticos/farmacocinética , Porosidad , Povidona/farmacocinética , Solubilidad , Comprimidos , Resistencia a la Tracción
8.
J Appl Toxicol ; 41(12): 2055-2067, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33993517

RESUMEN

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.


Asunto(s)
Caenorhabditis elegans/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Neuronas/efectos de los fármacos , Povidona/toxicidad , Plata/toxicidad , Animales , Caenorhabditis elegans/fisiología , Neuronas/fisiología , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/fisiopatología , Excipientes Farmacéuticos/toxicidad , Sustitutos del Plasma/toxicidad
9.
Mol Pharm ; 18(4): 1604-1621, 2021 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-33576626

RESUMEN

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.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Excipientes Farmacéuticos/química , Polímeros/química , Rifaximina/química , Química Farmacéutica , Cristalización , Enlace de Hidrógeno , Rifaximina/administración & dosificación , Solubilidad
10.
Yakugaku Zasshi ; 141(1): 47-53, 2021.
Artículo en Japonés | MEDLINE | ID: mdl-33390447

RESUMEN

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.


Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos , Indometacina/administración & dosificación , Nanopartículas , Soluciones Oftálmicas , Antiinflamatorios no Esteroideos/farmacocinética , Disponibilidad Biológica , Diseño de Fármacos , Endocitosis/fisiología , Epitelio Corneal , Humanos , Indometacina/farmacocinética , Excipientes Farmacéuticos , Solubilidad , Suspensiones
12.
Acta Radiol ; 62(12): 1559-1566, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33251810

RESUMEN

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.


Asunto(s)
Medios de Contraste/administración & dosificación , Aditivos Alimentarios/administración & dosificación , Intestino Delgado/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Abdomen/diagnóstico por imagen , Administración Oral , Anciano , Albúminas , Medios de Contraste/efectos adversos , Medios de Contraste/química , Huevos , Femenino , Aromatizantes , Aditivos Alimentarios/efectos adversos , Aditivos Alimentarios/química , Voluntarios Sanos , Humanos , Íleon/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Excipientes Farmacéuticos/administración & dosificación , Excipientes Farmacéuticos/efectos adversos , Excipientes Farmacéuticos/química , Fosfatos , Polisacáridos Bacterianos , Compuestos de Potasio , Dosis de Radiación , Estómago/diagnóstico por imagen , Agua
13.
Cornea ; 40(3): 383-386, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-32794685

RESUMEN

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.


Asunto(s)
COVID-19/virología , Conjuntiva/virología , Conjuntivitis Viral/virología , Infecciones Virales del Ojo/virología , Nasofaringe/virología , ARN Viral/genética , SARS-CoV-2/aislamiento & purificación , Administración Oftálmica , Administración Oral , Adulto , Antirreumáticos/uso terapéutico , Antivirales/uso terapéutico , COVID-19/diagnóstico , Prueba de Ácido Nucleico para COVID-19 , Conjuntivitis Viral/diagnóstico , Conjuntivitis Viral/tratamiento farmacológico , Quimioterapia Combinada , Infecciones Virales del Ojo/diagnóstico , Infecciones Virales del Ojo/tratamiento farmacológico , Ganciclovir/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Presión Intraocular , Masculino , Excipientes Farmacéuticos/uso terapéutico , Povidona/uso terapéutico , SARS-CoV-2/genética , Microscopía con Lámpara de Hendidura , Agudeza Visual , Tratamiento Farmacológico de COVID-19
14.
Pharm Res ; 37(12): 234, 2020 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-33123783

RESUMEN

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.


Asunto(s)
Competencia Clínica/estadística & datos numéricos , Composición de Medicamentos/historia , Excipientes Farmacéuticos/efectos adversos , Medicamentos bajo Prescripción/química , Prescripciones de Medicamentos , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Excipientes Farmacéuticos/química , Excipientes Farmacéuticos/historia , Medicamentos bajo Prescripción/efectos adversos , Medicamentos bajo Prescripción/historia , Encuestas y Cuestionarios/estadística & datos numéricos
15.
Mol Pharm ; 17(10): 3825-3836, 2020 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-32870691

RESUMEN

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.


Asunto(s)
Carbamazepina/química , Cristalización , Excipientes Farmacéuticos/química , Polímeros/química , Administración Oral , Rastreo Diferencial de Calorimetría , Química Farmacéutica , Derivados de la Hipromelosa/química , Solubilidad , Propiedades de Superficie , Agua , Difracción de Rayos X
16.
Mol Pharm ; 17(10): 3773-3782, 2020 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-32881529

RESUMEN

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.


Asunto(s)
Antineoplásicos/farmacocinética , Cinamatos/química , Portadores de Fármacos/química , Excipientes Farmacéuticos/química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Curcumina/administración & dosificación , Curcumina/química , Curcumina/farmacocinética , Liberación de Fármacos , Emulsiones , Femenino , Interacciones Hidrofóbicas e Hidrofílicas , Inyecciones Intravenosas , Ratones , Ratones Endogámicos ICR , Modelos Animales , Nanopartículas/química , Aceites/química , Paclitaxel/administración & dosificación , Paclitaxel/química , Paclitaxel/farmacocinética , Solubilidad
17.
United European Gastroenterol J ; 8(10): 1217-1227, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32838693

RESUMEN

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.


Asunto(s)
Colonoscopía/métodos , Laxativos/administración & dosificación , Excipientes Farmacéuticos/administración & dosificación , Cuidados Preoperatorios/métodos , Colonoscopía/estadística & datos numéricos , Humanos , Laxativos/efectos adversos , Laxativos/química , Evaluación del Resultado de la Atención al Paciente , Satisfacción del Paciente , Excipientes Farmacéuticos/química , Ensayos Clínicos Controlados Aleatorios como Asunto , Gusto , Resultado del Tratamiento
18.
Curr Drug Deliv ; 17(9): 736-754, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32729418

RESUMEN

Nowadays, the focus has been shifted to new technologies for improving drug solubility, permeability, and bioavailability, amid unprecedentedly increasing the number of newly discovered Active Pharmaceutical Ingredients (APIs), which are mostly categorized under Biopharmaceutical Classification System (BCS) as class-II and class IV. Traditional technologies and classical formulation strategies often fail to address most of the formulation problems associated with new APIs, particularly solubility and bioavailability. Therefore, exploring new and innovative technologies on an industrial scale is a prerequisite and requires modernization of manufacturing processes, as well as more advanced research and development. Liquisolid technology is a new, innovative industrial technology, particularly designed for either improving the release rates of poorly absorbed drugs or controlling their release pattern by achieving sustained-release profiles with zero-order release kinetics. Besides, it is a promising photoprotective system for photosensitive drugs and can further be used for modulating the drug microenvironmental pH. The next generation of liquisolid systems stems from a set of emerging technologies, such as liqui-pellet technology, which originates from combining liquisolid technology with pelletization technique, particularly extrusion-spheronization technique. This review article highlights the current state of liquisolid technology, ongoing challenges, characterization and applications, possible future prospects, the advent of new and emerging technologies, and the revolution of the next generation of liquisolid technology.


Asunto(s)
Química Farmacéutica/métodos , Preparaciones de Acción Retardada/farmacocinética , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Excipientes Farmacéuticos/química , Disponibilidad Biológica , Cápsulas , Química Farmacéutica/tendencias , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/química , Composición de Medicamentos/tendencias , Liberación de Fármacos , Modelos Biológicos , Porosidad , Literatura de Revisión como Asunto , Solubilidad , Propiedades de Superficie , Comprimidos
19.
Curr Drug Deliv ; 17(8): 720-726, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32640958

RESUMEN

OBJECTIVE: To prepare the sustained-release complex, quercetin was incorporated with ß- cyclodextrin (ß-CD) and the effect of ß-CD-quercetin complex on the growth of ethanol-injuried hepatocytes was studied. METHODS: By using scanning electron microscopy, infrared spectroscopy, and release rate analysis, ß- CD-quercetin complex was identified. The effect of different concentrations of ß-CD-quercetin complex on the growth of ethanol-damaged hepatocytes at different time was observed by using MTT assay, and the cell quantity and morphology were observed by using hematoxylin-eosin staining. By using single-cell gel electrophoresis, the prevention of ß-CD-quercetin complex from the DNA damage of ethanol-damaged BRL-3A cells was studied, and Olive tail moment was calculated. RESULTS: ß-CD-quercetin complex as the sustained-release complex was successfully prepared. The ethanol induced damage of BRL-3A cells could be prevented by 20, 40 and 80 mg/L of quercetin complex, and the protection mechanism of hepatocyte was related to the antioxidation of DNA. CONCLUSION: Quercetin sustained-release complex could be prepared with ß-CD, and it might be used to treat alcoholic liver disease.


Asunto(s)
Antioxidantes/farmacología , Hepatocitos/efectos de los fármacos , Hepatopatías Alcohólicas/tratamiento farmacológico , Quercetina/farmacología , beta-Ciclodextrinas/química , Animales , Antioxidantes/química , Antioxidantes/uso terapéutico , Línea Celular , Daño del ADN/efectos de los fármacos , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacología , Preparaciones de Acción Retardada/uso terapéutico , Modelos Animales de Enfermedad , Composición de Medicamentos/métodos , Etanol/toxicidad , Hepatocitos/patología , Humanos , Estrés Oxidativo/efectos de los fármacos , Excipientes Farmacéuticos/química , Quercetina/química , Quercetina/uso terapéutico , Ratas , Solubilidad
20.
Int J Mol Sci ; 21(11)2020 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-32512914

RESUMEN

In this study, an innovative methodology to optimize amorphization during the hot melt impregnation (HMI) process was proposed. The novelty of this report revolves around the use of thermal analysis in combination with design of experiments (DoEs) to reduce residual crystallinity during the HMI process. As a model formulation, a mixture of ibuprofen (IBU) and Neusilin was used. The main aim of the study was to identify the critical process parameters of HMI and determine their optimal values to assure a robust impregnation process and possibly the highest possible amorphization rate of IBU. In order to realize this, a DoE approach was proposed based on a face-centered composite design involving three factors. The IBU/Neusilin ratio, the feeding rate, and the screw speed were considered as variables, while the residual crystallinity level of IBU, determined using differential scanning calorimetry (DSC), was measured as the response. Additionally, the stability of IBU under HMI was analyzed using high-performance liquid chromatography to estimate the extent of potential degradation. In order to verify the correctness of the DoE model, tested extrudates were manufactured by HMI and the obtained extrudates were thoroughly examined using scanning electron micrography, X-ray powder diffraction, and DSC.


Asunto(s)
Tecnología de Extrusión de Fusión en Caliente/métodos , Rastreo Diferencial de Calorimetría , Química Farmacéutica/métodos , Cromatografía Líquida de Alta Presión , Ibuprofeno/química , Excipientes Farmacéuticos/química , Comprimidos , Difracción de Rayos X
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