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1.
Talanta ; 233: 122602, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215090

RESUMO

A smartphone-based technique for determining the titration equivalence point from a linear-segment curve was developed for the first time. In this method, a titrant in an increasing microliter-volume was added to a set of sample aliquots containing an indicator covering both sides of the equivalence point. The solutions were subsequently photographed in one shot, in a dark box using a smartphone camera and an illuminating screen of a tablet or light emitting diode lamps arranged below a white acrylic sheet as a light source. After the colors of the solutions were delineated to Red, Green, and Blue (RGB) values, 1/log G was used to construct a plot in which the equivalence point was located at the intersection of the two lines in the region before and after the equivalence point. The technique was successfully applied to the miniaturized titration of sodium chloride injections, showing the good linear relationship of equivalence points to the sodium chloride concentration in the range of 0.4163-0.9675% w/v (R2 of 0.9998). The assay was accurate (% recovery of 98.92-100.52), precise (% relative standard deviation ≤ 1.20), and unaffected by the use of different types of microplates, smartphones, and RGB analysis tools. Additionally, it required no expensive nor complicated equipment and offered the possibility of performing analysis on a single smartphone device when it was used with a mobile application developed to aid data processing and immediate production of reports of analytical results.


Assuntos
Smartphone , Cloreto de Sódio , Colorimetria , Comprimidos
2.
Georgian Med News ; (314): 172-179, 2021 May.
Artigo em Russo | MEDLINE | ID: mdl-34248050

RESUMO

According to the WHO data, over 35 million people in the world suffer from severe forms of cognitive impairment. Due to the insufficient effectiveness of separate therapy for amyloid or vascular pathologies, an opinion is expressed about the prospects of combined pharmacotherapy of cognitive impairments. The aim of the study was the pharmaceutical development of the combined tablet dosage form formulation with modified release of citicoline and memantine for the treatment of cognitive impairments. Information bases (eLibrary, PubMed) were used, content analysis on State Register of Medicinal Remedies database (grls.rosminzdrav.ru). The compatibility assessment was carried out by stress experiments method in combination with chromatographic analysis. Comparative pharmacokinetic studies were carried out on rabbits. The justification of the pharmacological and clinical feasibility of the proposed fixed dose combination has been carried out, the objective advantage of which is the potentiation of the pharmacotherapeutic action due to the unidirectional effect of memantine and citicoline, and the expected effect is to improve cognition, functioning and behavior and / or slow down their deterioration. The use of the combination will allow achieving ease of treatment, reducing costs, and, accordingly, compliance. The choice of the optimal dosage form for the developed combination was carried out: a tablet containing two release methods: memantine - immediate release, citicoline - prolonged release. The compatibility of the pharmaceutical substances memantine hydrochloride and citicoline monosodium salt with each other and the excipients planned for use in the formulation has been experimentally revealed. Comparative pharmacokinetic studies of the developed combined drug have been carried out.


Assuntos
Excipientes , Memantina , Animais , Preparações de Ação Retardada , Desenvolvimento de Medicamentos , Coelhos , Comprimidos
3.
Sensors (Basel) ; 21(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203526

RESUMO

A laboratory prototype for hyperspectral imaging in ultra-violet (UV) region from 225 to 400 nm was developed and used to rapidly characterize active pharmaceutical ingredients (API) in tablets. The APIs are ibuprofen (IBU), acetylsalicylic acid (ASA) and paracetamol (PAR). Two sample sets were used for a comparison purpose. Sample set one comprises tablets of 100% API and sample set two consists of commercially available painkiller tablets. Reference measurements were performed on the pure APIs in liquid solutions (transmission) and in solid phase (reflection) using a commercial UV spectrometer. The spectroscopic part of the prototype is based on a pushbroom imager that contains a spectrograph and charge-coupled device (CCD) camera. The tablets were scanned on a conveyor belt that is positioned inside a tunnel made of polytetrafluoroethylene (PTFE) in order to increase the homogeneity of illumination at the sample position. Principal component analysis (PCA) was used to differentiate the hyperspectral data of the drug samples. The first two PCs are sufficient to completely separate all samples. The rugged design of the prototype opens new possibilities for further development of this technique towards real large-scale application.


Assuntos
Imageamento Hiperespectral , Preparações Farmacêuticas , Acetaminofen , Aspirina , Ibuprofeno , Comprimidos
4.
Ceska Slov Farm ; 70(2): 66-78, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34237946

RESUMO

The aim of this work was to develop anti-stress compressed lozenges containing 100 mg of glycine and 250 mg of magnesium citrate obtained by the direct compression method. To choose optimal excipient composition providing the sufficient pharmaco-technical properties of the tablet blend, mechanical strength of tablets and non-disintegrating, slow-dissolving behavior of compressed lozenges during sucking, 27 experimental formulations according to fractional factorial Latin cube design were prepared and tested. The excipients used in the study were: Mannogem® EZ, Cellactose® 80 and GalenIQ 721 (fillers); Plasdone S-630, Kollidon® 90 F and Avicel® PH-101 (dry binders); Metolose® 90SH-4000SR and guar gum (gel-forming binders); PRUV®, Neusilin® US2, and Compritol® 888 CG ATO (antifriction excipients). The following parameters were investigated as responses: bulk density, Carrs index, friability, resistance to crushing, and in vitro disintegration time. ANOVA approach was applied for statistical processing, which allowed to reveal the individual effects of each excipient and several interaction effects observed for the excipient amounts used in this study. Isomalt (GalenIQ 721), copovidone (Plasdone S-630), and glyceryl behenate (Compritol® 888 CG ATO) were selected to be incorporated in the final formulation of compressed lozenges.


Assuntos
Celulose , Excipientes , Análise de Variância , Solubilidade , Comprimidos
5.
BMC Res Notes ; 14(1): 254, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193274

RESUMO

OBJECTIVE: To evaluate in-vitro quality of paracetamol 500 mg tablet brands marketed in Saudi Arabia. RESULTS: Two reference (R1 and R2) and seven generic (G1-G7) brands were commercially available. Four brands were single-drug, containing paracetamol only (R1, G1-G3) and five contained additional active ingredients (R2, G4-G7). All brands were immediate-release. Weight variation (n = 20, range as percent difference from mean), active substance content (n = 20, mean (SD) as percent difference from label), breaking force (n = 10, mean (SD)), and friability (n = 20, as percent weight loss) ranged from 97 to 102%, 96.1% (2.9%) to 99.8% (1.1%), 9.9 (0.4) to 21.0 (0.9) kg, and 0.017% to 0.809%, respectively. Disintegration (water medium) time (n = 6, minute: second) ranged from 02:35-03:09 to 12:49-13:10. Dissolution (phosphate buffer, pH 5.8) profile showed a mean release at 30 min of 87% to 97% of label content, with seven brands passing stage-1 (≥ 85% for each of 6 test units) and two passing stage-2 (mean of 12 test units ≥ 85%) criteria. Despite statistically significant differences between R1 and R2 and some of their corresponding generic brands in active substance content, breaking force, and amount dissolved at 30 min, all nine brands met the pre-specified quality standards.


Assuntos
Acetaminofen , Medicamentos Genéricos , Controle de Qualidade , Arábia Saudita , Comprimidos
6.
Ars pharm ; 62(2): 144-162, abr.-jun. 2021. tab, graf
Artigo em Inglês | IBECS | ID: ibc-202441

RESUMO

INTRODUCTION: The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and release the drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach. METHOD: Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes) were identified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23 factor experimental design with midpoints was selected for statistical analysis and optimization. RESULTS: HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit's stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2 of an optimized product when compared to the marketed product. CONCLUSIONS: It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula


INTRODUCCIÓN: Los inconvenientes de la administración oral pueden controlarse o minimizarse mediante formulaciones gastro-retentivas que permanecen flotantes dentro del estómago durante un tiempo prolongado al proporcionar una retención gástrica prolongada y liberan el fármaco de una manera excesivamente prolongada mejorando así la biodisponibilidad. La investigación actual fue desarrollar y optimizar las tabletas flotantes de domperidona y famotidina con liberación prolongada mediante el enfoque Calidad por diseño. MÉTODO: Basado en QTPP (Perfil de producto objetivo de calidad), se identificaron CQA (Atributos críticos de calidad). El análisis de riesgos mediante la evaluación de los parámetros de formulación y proceso mostró que la optimización de los niveles de polímeros podría reducir el alto riesgo para lograr el perfil objetivo. Se seleccionó un diseño experimental de 2 factores de nivel 3 con puntos medios para el análisis estadístico y la optimización. RESULTADOS: HPMC K100, Carbopol 934P tuvo un efecto positivo y la etilcelulosa tuvo un efecto negativo sobre las respuestas seleccionadas. La cinética de liberación del fármaco siguió a la liberación de primer orden con difusión de Higuchi y difusión de Fickian. Se seleccionó y evaluó una fórmula optimizada que satisfacía todos los parámetros requeridos. Los valores de respuesta previstos estaban en estrecha concordancia con los valores de respuesta experimental. Las imágenes de rayos X abdominales después de la administración oral de las tabletas en el estómago sano del conejo confirmaron el comportamiento de flotación prolongado con un tiempo de retraso más corto. Losin vivo estudios farmacocinético sen conejos revelaron que la formulación optimizada exhibía una liberación prolongada del fármaco con una mayor Cmax, tmax, AUCo-t y t1 / 2 del producto. CONCLUSIONES: Se concluyó que la aplicación de Quality by Design en la formulación y optimización redujo el número de ensayos para producir una fórmula rentable


Assuntos
Animais , Coelhos , Sistemas de Liberação de Medicamentos/métodos , Domperidona/farmacologia , Famotidina/farmacologia , Antieméticos/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Liberação Controlada de Fármacos , Desenho de Fármacos , Combinação de Medicamentos , Fatores de Tempo , Disponibilidade Biológica , Medição de Risco , Comprimidos/farmacologia
7.
Ars pharm ; 62(2): 190-202, abr.-jun. 2021. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-202445

RESUMO

INTRODUCCIÓN: Los estudios gauge permiten ganar información sobre el desempeño de procesos y son de utilidad para control de calidad, así como identificación de fuentes de variación. El objetivo del presente estudio, fue diseñar y analizar sistemas de medición para los modelos de Heckel y Ryshkewitch-Duckworth para caracterizar materiales, a través de estudios Gauge R&R. MÉTODO: Estudio Gauge R&R cruzado para evaluar el sistema de medición del peso y estudio Gauge R&R anidado para el sistema de la resistencia a la fractura. RESULTADOS: Ambos estudios cumplieron con los supuestos de normalidad, varianza constante e independencia de los datos, por lo que fue posible determinar la significación de las fuentes de variación (factores) mediante un ANOVA así como su porcentaje de contribución. Para el estudio Gauge R&R cruzado los punzones evaluados contribuyen a la variación de la medición de manera significativa y en un 97,38% de la variación total; los operadores contribuyen en menos del 1% y de manera no significativa y no existió interacción parte-operador. Respecto al estudio Gauge R&R anidado, se identificó que el operador no influyó de manera significativa en la variabilidad de la medición y que ésta es atribuible en un 95% a las diferencias existentes entre las tabletas evaluadas. CONCLUSIONES: Se realizó el diseño, ejecución y análisis de los sistemas de medición, destacando que en ambos estudios la principal fuente de variación fueron las partes evaluadas y que los operadores no contribuyen en la variabilidad de las mediciones, por lo que los estudios pueden usarse para evaluar los modelos matemáticos y durante el control estadístico de un proceso


INTRODUCTION: Gauge studies allow gaining information about the performance of processes and are very useful tools for quality control and identification of variability sources. The objective of the present study was design and analyzes measurement systems for the Heckel and Ryshkewitch-Duckworth models for characterizing materials, through Gauge R&R studies. METHOD: Crossed Gauge R&R study for the evaluation of weight measurement system and nested Gauge R&R study for the system of tablet hardness. RESULTS: Both studies fulfilled with the assumptions of normality, constant variance and data independence, therefore it was possible to estimate the significance of variation sources (factors) through ANOVA and their contribution percentage. The crossed Gauge R&R study showed that the flat punches contributed to variability of the measurement in a significant manner in 97.38% of the total variation of the study; operators did it in less than 1% and they were not statistically significant and there was no Part-Operator interaction. With respect to the nested Gauge R&R study, it was found that the operator did not influence in a statistically significant way in the variability of the measurement and it was attributable in 95% to the existing differences between the tablets evaluated. CONCLUSIONS: Design, run and analysis of the measurement systems was performed, we remark that in both of the studies the main source of variability were the parts evaluated and that operators did not contribute to variability in the measurements; therefore, both studies could be used to evaluate the Heckel and Ryshkewitch-Duckworth mathematical models and also for statistical process control


Assuntos
Modelos Teóricos , Comprimidos/normas , Teste de Materiais/normas , Controle de Qualidade , Valores de Referência , Resistência à Flexão , Análise de Variância , Reprodutibilidade dos Testes
8.
Gen Dent ; 69(4): 19-26, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34185664

RESUMO

The objectives of this study were to determine the effectiveness of a mucoadhesive tablet of pilocarpine, 5 mg, for the treatment of xerostomia and verify its pharmacokinetic profile. The randomized, double-blind, crossover clinical trial involved 25 older adults (60 to 80 years) with xerostomia and hyposalivation who were randomly divided into groups A and B. Once daily, for 7 days, group A used a mucoadhesive tablet containing pilocarpine, while group B used a mucoadhesive tablet without the active ingredient (first intervention). After 7 days of washout (no treatment), use of the medications resumed for 7 days, with a crossover between groups (second intervention). Xerostomia was evaluated through a shortened version of the Summated Xerostomia Inventory-Dutch Version, and the unstimulated salivary flow (USF) and stimulated salivary flow (SSF) of the patients were measured. The patients were evaluated at baseline and 7, 14, and 21 days. Then, the pharmacokinetic profiles of mucoadhesive and conventional oral pilocarpine tablets were compared using saliva obtained from 8 patients. Both of the interventions resulted in a significant reduction in Summated Xerostomia Inventory scores and a significant increase in the mean USF (P < 0.05). A statistically significant increase in the mean SSF only occurred when pilocarpine was administered (P < 0.05). No significant adverse effects were found. The mucoadhesive tablet resulted in much higher salivary concentrations of pilocarpine than did the conventional oral tablet. Both formulations of the mucoadhesive tablet, with or without pilocarpine, relieved patients' dry mouth symptoms. Trial registration: Registro Brasileiro de Ensaios Clinicos (ReBEC) No. RBR-9qdnws.


Assuntos
Pilocarpina , Xerostomia , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Humanos , Pessoa de Meia-Idade , Saliva , Comprimidos , Xerostomia/tratamento farmacológico
9.
AAPS PharmSciTech ; 22(5): 167, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34080078

RESUMO

In developing countries, populations have employed herbal medicines for primary health care because they are believed to be more appropriate to the human body and have less side effects than chemically synthesized drugs. The present study aimed to develop and evaluate herbal tablets incorporated with a Thai traditional medicinal extract, U-pa-ri-waat (URW), using microwave-assisted extraction (MAE). The extraction efficiency for URW using MAE and traditional solvent extraction was compared based on the percent yield after spray drying. URW tablets were prepared using the dry granulation method. The optimized products were assessed using standard characterization methods based on the United States and British Pharmacopeias. DPPH and ABTS radical scavenging assays were performed to analyze the antioxidant capacity of the microwave-assisted extracts. The results revealed that the flowability of the dry granule with added maltodextrin was improved compared to a granule without additives, as indicated by an angle of repose of 33.69 ± 2.0°, a compressibility index of 15.38 ± 0.66, and a Hausner's ratio of 1.18 ± 0.06. The resulting formulation produced flat tablets with uniform weight variation, hardness, thickness, friability, and optimum disintegration time. The URW extracts showed antioxidant activity and MAE with maltodextrin carrier displayed the strongest DPPH and ABTS radical activities with IC50 values of 1.60 ± 0.02 µg/mL and 4.02 ± 0.24 µg/mL, respectively. The URW tablet formulation passed the quality control tests. Storage of the formulation tablets for 90 days under accelerated conditions had minimal effects on tablet characteristics.


Assuntos
Química Farmacêutica/métodos , Micro-Ondas , Compostos Fitoquímicos/síntese química , Preparações de Plantas/síntese química , Administração Oral , Antioxidantes/administração & dosagem , Antioxidantes/síntese química , Antioxidantes/farmacocinética , Avaliação Pré-Clínica de Medicamentos/métodos , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/farmacocinética , Medicina Herbária/métodos , Humanos , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/farmacocinética , Preparações de Plantas/administração & dosagem , Preparações de Plantas/farmacocinética , Comprimidos , Tailândia
10.
AAPS PharmSciTech ; 22(5): 183, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34132921

RESUMO

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.


Assuntos
Carboximetilcelulose Sódica/síntese química , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Povidona/síntese química , Carboximetilcelulose Sódica/farmacocinética , Avaliação Pré-Clínica de Medicamentos/métodos , Excipientes/síntese química , Excipientes/farmacocinética , Excipientes Farmacêuticos/síntese química , Excipientes Farmacêuticos/farmacocinética , Porosidade , Povidona/farmacocinética , Solubilidade , Comprimidos , Resistência à Tração
11.
Eur J Pharm Sci ; 164: 105907, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34118411

RESUMO

Electrospinning is a technology for manufacture of nano- and micro-sized fibers, which can enhance the dissolution properties of poorly water-soluble drugs. Tableting of electrospun fibers have been demonstrated in several studies, however, continuous manufacturing of tablets have not been realized yet. This research presents the first integrated continuous processing of milled drug-loaded electrospun materials to tablet form supplemented by process analytical tools for monitoring the active pharmaceutical ingredient (API) content. Electrospun fibers of an amorphous solid dispersion (ASD) of itraconazole and poly(vinylpyrrolidone-co-vinyl acetate) were produced using high speed electrospinning and afterwards milled. The milled fibers with an average fiber diameter of 1.6 ± 0.9 µm were continuously fed with a vibratory feeder into a twin-screw blender, which was integrated with a tableting machine to prepare tablets with ~ 10 kN compression force. The blend of fibers and excipients leaving the continuous blender was characterized with a bulk density of 0.43 g/cm3 and proved to be suitable for direct tablet compression. The ASD content, and thus the API content was determined in-line before tableting and at-line after tableting using near-infrared and Raman spectroscopy. The prepared tablets fulfilled the USP <905> content uniformity requirement based on the API content of ten randomly selected tablets. This work highlights that combining the advantages of electrospinning (e.g. less solvent, fast and gentle drying, low energy consumption, and amorphous products with high specific surface area) and the continuous technologies opens a new and effective way in the field of manufacturing of the poorly water-soluble APIs.


Assuntos
Excipientes , Análise Espectral Raman , Dessecação , Composição de Medicamentos , Itraconazol , Comprimidos , Tecnologia Farmacêutica
12.
Molecules ; 26(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067434

RESUMO

The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics.


Assuntos
Química Farmacêutica/métodos , Cetoprofeno/química , Cetoprofeno/síntese química , Impressão Tridimensional , Comprimidos , Varredura Diferencial de Calorimetria , Preparações de Ação Retardada , Composição de Medicamentos/métodos , Desenho de Fármacos , Liberação Controlada de Fármacos , Elasticidade , Excipientes/química , Álcool de Polivinil , Medicina de Precisão , Reprodutibilidade dos Testes , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Difração de Raios X , Microtomografia por Raio-X
13.
Drug Dev Ind Pharm ; 47(5): 778-789, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34082622

RESUMO

OBJECTIVE: The generic drug product DRL ABC is an Extended Release (ER) Tablet manufactured by Dr. Reddy's Laboratories Limited and have multi point dissolution as part of release specification. A proposal is being made to revise the dissolution specification and the aim of present work was to evaluate if this would still provide bioequivalent product. METHODS: PBBM was developed for DRL ABC using literature reported pharmacokinetic (PK) data. The intravenous PK data and in vitro metabolic rate constants were utilized for developing PBPK model first, followed by that in conjugation with mechanistic ACATTM model, a PBBM is developed for per-oral immediate release formulations. The validated model was applied to predict clinical bioequivalence (BE) study data for the Reference (Innovator ER Tablet) and Test product. For Reference and Test product, in vivo dissolution profiles were mechanistically deconvoluted from plasma concentration (Cp)-time profiles. Further, mechanistic in vitro-in vivo relationship (IVIVR) applied to in vitro release profiles of two hypothetical Test product batches (one with single point low dissolution profile (SPLP) and other with overall low dissolution profile (LP)) in order to calculate their in vivo releases and population simulation was performed with 40 virtual subjects. RESULTS: Results from the cross-over virtual trials showed BE between the Reference and various Test product batches (SPLP and LP), with maximum Cp (Cmax) and area under the Cp-time curve (AUC0-inf) well within 80-125% range. CONCLUSION: PBBM in conjugation with IVIVR and virtual BE was successfully applied for justifying changes in dissolution specification of DRL ABC.


Assuntos
Biofarmácia , Modelos Biológicos , Administração Oral , Humanos , Solubilidade , Comprimidos , Equivalência Terapêutica
14.
Medicine (Baltimore) ; 100(25): e26369, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160409

RESUMO

BACKGROUND: Diseases of the oral cavity (OC) with an infectious trigger such as caries and periodontal disease are extremely common in the general population and can also have effects at the cardiovascular level. The oral salivary flow, with its buffering capacity, is able to regulate the pH of the OC and, therefore, significantly contribute to the ecological balance of the microenvironment in which the oral microbiome (OM) develops. On the other side, when the quality/quantity of salivary flow is altered it is supposed the disruption of this balance with the potential increase in oral pathogens and triggered diseases. Among the endogenous substances able to exert a significant effect on the salivary flow and its characteristics, carnosine (Car), a dipeptide originally isolated in skeletal muscle, represents, thanks to the known buffering properties, a promising principle. METHODS: We aimed this protocol to evaluate the quantitative/qualitative characteristics of the salivary flow in healthy volunteer subjects (n = 20) and in subjects suffering from common OC pathologies (n = 40), before and after 7 days of supplementation with SaliflussTM (Metis Healthcare srl, Milan, Italy), a Class I medical device on the market as 400 mg mucoadhesive oral tablets that has Car as the main ingredient. DISCUSSION: Combining the characteristics of saliva with the OM and comparing them with OC pathologies, we expect to clarify their reciprocal relationship and, using quantitative proteomics techniques, to help clarify the mechanism of action of Car.


Assuntos
Carnosina/administração & dosagem , Cárie Dentária/dietoterapia , Gengivite/dietoterapia , Periodontite/dietoterapia , Saliva/química , Administração Bucal , Adolescente , Adulto , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Cárie Dentária/complicações , Cárie Dentária/prevenção & controle , Suplementos Nutricionais , Gengivite/microbiologia , Gengivite/prevenção & controle , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Masculino , Microbiota/fisiologia , Mucosa Bucal/microbiologia , Periodontite/microbiologia , Periodontite/prevenção & controle , Saliva/metabolismo , Comprimidos , Adulto Jovem
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 261: 119984, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34087772

RESUMO

An innovative and sensitive spectrofluorimetric method has been developed for determination of 6-aminocaproic acid (ACA) in its pure form and its laboratory prepared tablets. The aim of this method is the reaction of ethyl acetoacetate and formaldehyde with the primary amino group presented in ACA as aimed in the Hantzsch reaction, this reaction resulted in formation of a yellow fluorescent dihydropyridine derivative that can be easily detected spectrofluorimetrically at 438 nm (excitation at 358 nm). At the optimum conditions of the reaction, the linear range was found to be (0.7-3.5 µg\mL) with limit of detection is 0.231 µg\mL and limit of quantitation is 0.700 µg\mL. The proposed method used for detection of ACA laboratory prepared tablets with average percentage 100.721 ±â€¯0.701% without any interference from any excipients. This method used for in vitro determination of ACA in spiked human plasma with a percent mean recovery 99.874 ±â€¯1.416%. In addition, the developed method used for determination of ACA in spiked human urine with percent mean recovery 100.314 ±â€¯1.793%.


Assuntos
Ácido Aminocaproico , Formaldeído , Excipientes , Humanos , Espectrometria de Fluorescência , Comprimidos
16.
Ther Deliv ; 12(7): 523-538, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098729

RESUMO

Background: Orally disintegrating tablets rapidly disintegrate in saliva and then swallowed without the need for water. Materials & methods: The orally disintegrating tablets were prepared by freeze-drying of an aqueous dispersion of isosorbide dinitrate containing a matrix former (gelatin), a cryoprotectant (mannitol), a plasticizer (glycerin) and a dissolution enhancer (Tween/polyethylene glycol). Results: Results demonstrated that the selected formulation, Ft9, disintegrated within 1 min and showed faster dissolution rate compared with the commercial tablet. Conclusion: Having a fast disintegration time, the developed lyophilized tablet does not need to be swallowed as a whole. So, it is a convenient solid oral dosage form for the patients who have difficulty with swallowing such as the pediatric and elderly ones.


Assuntos
Sistemas de Liberação de Medicamentos , Dinitrato de Isossorbida , Administração Oral , Idoso , Criança , Liofilização , Humanos , Solubilidade , Comprimidos
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 261: 120045, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34126397

RESUMO

A very simple, economic analytical method with few sample pretreatment steps has been developed for quantitation of simvastatin in the presence of its isostructure lovastatin without any interference. It was utilized for easy and complete fine characterization of simvastatin FTIR spectrum from that of lovastatin. Simvastatin has been determined efficiently by the developed method either alone or in mixture with lovastatin giving LOQ values of 0.009 and 0.02% w/w, respectively indicating good sensitivity. Acceptable correlation coefficient values of 0.9975 and 0.9886 alone and in mixture with lovastatin, respectively. The developed spectroscopic method has provided simple and sensitive tool in quality control laboratories for efficient quantitation simvastatin in pharmaceutical tablets with good recoveries.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Lovastatina , Sinvastatina , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos
18.
BMC Infect Dis ; 21(1): 595, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34157984

RESUMO

BACKGROUND: We aimed to assess the overall cardiovascular and metabolic effect of the switch to three different single tablet regimens (STRs) [tenofovir alafenamide/emtricitabine/rilpivirine (TAF/FTC/RPV), TAF/FTC/elvitegravir/cobi (TAF/FTC/EVG/cobi) and ABC/lamivudine/dolutegravir (ABC/3TC/DTG)] in a cohort of people living with HIV/AIDS (PLWH) under effective ART. METHODS: All PLWH aged above 18 years on antiretroviral treatment with an HIV-RNA < 50 cp/mL at the time of the switch to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG were retrospectively included in the analysis. Framingham risk score modification after 12 months from the switch such as lipid profile and body weight modification were assessed. The change from baseline to 12 months in mean cardiovascular risk and body weight in each of the STR's group were assessed by means of Wilcoxon signed-rank test whereas a mixed regression model was used to assess variation in lipid levels. RESULTS: Five-hundred and sixty PLWH were switched to an STR regimen of whom 170 (30.4%) to TAF/FTC/EVG/cobi, 191 (34.1%) to TAF/FTC/RPV and 199 (35.5%) to ABC/3TC/DTG. No difference in the Framingham cardiovascular risk score was observed after 12 months from the switch in each of the STR's groups. No significant overtime variation in mean total cholesterol levels from baseline to 12 months was observed for PLWH switched to ABC/3TC/DTG [200 (SD 38) mg/dl vs 201 (SD 35) mg/dl; p = 0.610] whereas a significant increment was observed in PLWH switched to TAF/FTC/EVG/cobi [192 (SD 34) mg/dl vs 208 (SD 40) mg/dl; p < 0.0001] and TAF/FTC/RPV [187 (SD 34) mg/dl vs 195 (SD 35) mg/dl; p = 0.027]. In addition, a significant variation in the mean body weight from baseline to 12 months was observed in PLWH switched to TAF/FTC/EVG/cobi [72.2 (SD 13.5) kilograms vs 74.6 (SD 14.3) kilograms; p < 0.0001] and TAF/FTC/RPV [73.4 (SD 11.6) kilograms vs 75.6 (SD 11.8) kilograms; p < 0.0001] whereas no difference was observed in those switched to ABC/3TC/DTG [71.5 (SD 12.8) kilograms vs 72.1 (SD 12.6) kilograms; p = 0.478]. CONCLUSION: No difference in the cardiovascular risk after 1 year from the switch to these STRs were observed. PLWH switched to TAF/FTC/EVG/cobi and TAF/FTC/RPV showed an increase in total cholesterol levels and body weight 12 months after the switch.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Combinação Emtricitabina, Rilpivirina e Tenofovir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/uso terapêutico , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Piridonas/uso terapêutico , Adulto , Fármacos Anti-HIV/metabolismo , Peso Corporal/efeitos dos fármacos , Estudos de Coortes , Didesoxinucleosídeos/metabolismo , Combinação de Medicamentos , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/metabolismo , Combinação Emtricitabina, Rilpivirina e Tenofovir/metabolismo , Feminino , Fatores de Risco de Doenças Cardíacas , Compostos Heterocíclicos com 3 Anéis/metabolismo , Humanos , Itália/epidemiologia , Lamivudina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Oxazinas/metabolismo , Piperazinas/metabolismo , Piridonas/metabolismo , Estudos Retrospectivos , Comprimidos/uso terapêutico
19.
AAPS PharmSciTech ; 22(5): 190, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34159445

RESUMO

In direct compression of tablets, it is crucial to maintain content uniformity within acceptable margins, especially in formulations with low drug loading. To assure it, complex and multistep mixing processes are utilized in the industry. In this study, we suggest the use of a simple segregation test to evaluate mixing process performance and mixture segregation to produce tablets having satisfying content uniformity while keeping the process as simple and low cost as possible. Eventually, the formulation propensity to segregation can be evaluated using process analytical technology (PAT) to adjust the mixing process parameters to changing source drug properties. In this study, that approach was examined on a model drug with a broad batch-to-batch variability in particle size and shape. Excipients were chosen so that the resulting blend composition mimicked some marketed formulations. For each drug batch, two formulation blends were prepared through different preparation processes (one simple and one complex) and subsequently subjected to segregation tests. From those, segregation coefficients were obtained to compare segregation tendencies and homogeneity robustness between the drug batches and the blend preparation methods. The inter-particulate interactions were substantially influenced by the drug particle morphology and size and resulted in different segregation behavior. Based on these findings, a simple segregation test proved to be a useful tool for determining the suitability of different batches of the model drug to be used in a certain formulation. Moreover, for a particular batch A, the test revealed a potential for mixing process simplification and therefore process intensification and cost reduction.


Assuntos
Composição de Medicamentos/métodos , Excipientes/síntese química , Tamanho da Partícula , Tecnologia Farmacêutica/métodos , Pós , Pressão , Comprimidos
20.
Ther Deliv ; 12(7): 539-552, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34165001

RESUMO

Aim: The present study focused on the development of a dry emulsion tablet of raloxifene hydrochloride (RXF) using a solid carrier adsorption technique to enhance oral bioavailability. Methods: An oil-in-water emulsion was formulated and converted into dry powder using HPMC K4M plus Aerosil 200, then compressed into tablets. Results: The prepared emulsion was evaluated for globule size, drug content and zeta potential. In vitro release study revealed significantly higher release from emulsion. The prepared tablets possessed acceptable hardness, friability, weight variation, disintegration time, thickness, etc. In vivo pharmacokinetic studies indicated a more than sevenfold increase in oral bioavailability. Stability studies indicated good physical and chemical stability of the developed formulation. Conclusion: The authors successfully formulated dry emulsion tablets with enhanced oral bioavailability.


Assuntos
Cloridrato de Raloxifeno , Adsorção , Disponibilidade Biológica , Emulsões , Solubilidade , Comprimidos
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