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1.
PLoS One ; 15(2): e0223201, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32050259

RESUMEN

The objective of this study was based on the formulation development of fast dispersible Aceclofenac tablets (100 mg) and to evaluate the influence of pharmaceutical mixtures of directly compressible Avicel PH102 with Mannitol and Ac-di-sol on the compressional, mechanical characteristics and drug release properties. Fast dispersible Aceclofenac formulations were developed by central composite design (CCD). Among them the best possible formulation was selected on the basis of micromeritic properties, appropriate tablet weight and disintegration time for further study. Tablets were directly compressed using manual hydraulic press with a compressional force ranging from 7.2 to 77.2 MN/m2. Pre and post compression studies were performed and the compressed formulations (FA-FF) were assessed for different quality tests. The Heckel and Kawakita equations were applied for determination of compressional behavior of formulations. The quality attributes suggested that formulation (FB) containing avicel PH 102 (20%), mannitol (25%) and ac-di-sol (3%) as best optimized formulation showing better mechanical strength i.e. hardness 35.40 ± 6.93N, tensile strength 0.963 MN/m2, and friability 0.68%. Furthermore, compressional analysis of FB showed lowest PY value 59.520 MN/m2 and Pk value 1.040 MN/m2 indicating plasticity of the material. Formulation FB disintegrated rapidly within 21 seconds and released 99.92% drug after 45 min in phosphate buffer pH 6.8. Results of drug release kinetics showed that all formulations followed Weibull and First-order models in three different dissolution media. Avicel PH102 based formulation mixture exhibit excellent compactional strength with rapid disintegration and quick drug release.


Asunto(s)
Química Farmacéutica/métodos , Diclofenaco/análogos & derivados , Composición de Medicamentos/métodos , Estrés Mecánico , Comprimidos/química , Antiinflamatorios no Esteroideos/química , Fuerza Compresiva , Diclofenaco/química , Dureza , Cinética , Solubilidad , Resistencia a la Tracción
2.
Int J Pharm Compd ; 24(1): 7-12, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32023210

RESUMEN

Minimizing contamination by airborne particulates is essential in pharmaceutical compounding, and biosafety cabinets have long been among the most effective types of equipment used to achieve that goal. In this article, which is the second of a 2-part series on primary engineering controls, the 3 classes and various types of biosafety cabinets are reviewed. In those units, directed airflow and high-efficiency particulate air filtration sweep airborne contaminants away from the operator, the preparation, and/ or the environment. Factors to consider before operating a Class-2 biosafety cabinet (the unit most often used in compounding) are briefly discussed, information about technician certification and training is reviewed, and diagrams demonstrating the mechanism of operation of several Class-2 units are provided. In part 1 of this series, other types of primary engineering controls used in compounding (unidirectional airflow workstations, compounding aseptic isolators, and compounding aseptic containment isolators) are discussed.


Asunto(s)
Contención de Riesgos Biológicos , Contaminación de Medicamentos , Composición de Medicamentos/métodos , Filtración
3.
Int J Pharm Compd ; 24(1): 38-43, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32023215

RESUMEN

Pharmaceutical formulation involves patient acceptability and compliance, ease of preparation, microbiological considerations, and chemical and physical factors affecting compatibility of all ingredients and stability. Physical factors such as light, heat, and humidity can trigger or accelerate undesirable chemical reactions such as oxidation, hydrolysis, decarboxylation, racemization, and photolysis, compromising drug stability. Many drug products and preparations are subject to oxidation, which can often be catalyzed by light, temperature, hydrogen ion concentration, presence of trace metals, or peroxides. Oxidation of a product may be manifested as an unpleasant odor or taste, discoloration or other change in appearance, precipitation, or even a slight loss of activity. Antioxidants are often introduced to improve the shelf life of pharmaceuticals along with suggested procedures to minimize oxidation. Often, chelating agents are added with antioxidants to bind with any trace metals present and enhance the stability of the formulation.


Asunto(s)
Antioxidantes , Composición de Medicamentos/métodos , Excipientes , Quelantes/química , Estabilidad de Medicamentos , Humanos
4.
Int J Pharm Compd ; 24(1): 77-82, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32023219

RESUMEN

This study reports on the stability of United States Pharmacopeia-grade metronidazole powder and commercially available metronidazole tablets in two dye-free oral suspending vehicles, namely Oral Mix and Oral Mix Sugar-Free. Metronidazole at 50 mg/mL was prepared individually in Oral Mix and Oral Mix Sugar-Free suspension vehicles and placed in 50-mL amber polyethyleneterephthalate bottles and 3-mL amber plastic syringes and stored at 4°C or 25°C/60% relative humidity for 90 days. The solutions were analyzed at the time of preparation and at 7 days, 14 days, 30 days, 45 days, 60 days, 75 days, and 90 days, with the concentration of metronidazole measured by high-performance liquid chromatography with photodiode array detection. The oral solutions were also monitored for pH, homogeneity, color, and odor. Except for the Oral Mix suspension of metronidazole prepared from the United States Pharmacopeia-grade powder and from the commercial tablet, when stored in pre-filled syringes, all the other preparations were stable at 4°C or 25°C/60% relative humidity for 90 days, with the metronidazole remaining within ± 10% of the initial concentration. The pH, color, odor, and resuspendability remained essentially unchanged. Metronidazole in Oral Mix and Oral Mix Sugar-Free oral suspensions, compounded from United States Pharmacopeia-grade powder or commercially available tablets, are a suitable alternative as an extemporaneously prepared medication.


Asunto(s)
Metronidazol , Administración Oral , Cromatografía Líquida de Alta Presión , Composición de Medicamentos/métodos , Estabilidad de Medicamentos , Suspensiones , Comprimidos/administración & dosificación , Estados Unidos
5.
Pharm Res ; 37(3): 43, 2020 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-31989336

RESUMEN

PURPOSE: Pyrvinium pamoate (PP) is an anthelmintic drug that has been found to have anti-cancer activity in several cancer types. In the present study, we evaluated PP for potential anti-leukemic activity in B cell acute lymphoblastic leukemia (ALL) cell lines, in an effort to evaluate the repurposing potential of this drug in leukemia. METHODS: ALL cells were treated with PP at various concentrations to determine its effect on cell proliferation. Metabolic function was tested by evaluating Extracellular Acidification Rate (ECAR) and Oxygen Consumption Rate (OCR). Lastly, 3D spheroids were grown, and PP was reformulated into nanoparticles to evaluate distribution effectiveness. RESULTS: PP was found to inhibit ALL proliferation, with varied selectivity to different ALL cell subtypes. We also found that PP's cell death activity was specific for leukemic cells, as primary normal immune cells were resistant to PP-mediated cell death. Metabolic studies indicated that PP, in part, inhibits mitochondrial oxidative phosphorylation. To increase the targeting of PP to a hypoxic bone tumor microenvironment (BTME) niche, we successfully encapsulated PP in a nanoparticle drug delivery system and demonstrated that it retained its anti-leukemic activity in a hemosphere assay. CONCLUSION: We have demonstrated that PP is a novel therapeutic lead compound that counteracts the respiratory reprogramming found in refractory ALL cells and can be effectively formulated into a nanoparticle delivery system to target the BTME.


Asunto(s)
Antineoplásicos/farmacología , Huesos/efectos de los fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Compuestos de Pirvinio/farmacología , Microambiente Tumoral/efectos de los fármacos , Muerte Celular , Línea Celular Tumoral , Proliferación Celular , Composición de Medicamentos/métodos , Liberación de Fármacos , Humanos , Nanocápsulas/química , Fosforilación , Transducción de Señal
6.
J Food Sci ; 85(2): 394-403, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31976556

RESUMEN

The delivery of active probiotic cells in capsules can reduce probiotic cell loss induced by detrimental external factors during digestion. In this study, we determined the optimal conditions for the encapsulation of Weissella cibaria JW15 (JW15) within calcium and polyethylene glycol (PEG)-alginate with chicory root extract powder (CREP). JW15 was encapsulated as the core material (109 cells/mL, 2 mL/min), and a solution containing a mixture of 1.5% sodium alginate and 1% CREP was extruded into a receiving bath with 0.1 M calcium chloride (CaCl2 ) and 0.05% PEG. Capsule morphology and size were measured using optical microscopy. The optimal air pressure and frequency vibration for capsules containing alginate only (Al) were 200 mbar and 200 Hz, respectively and 100 mbar and 350 Hz for capsules containing alginate with CREP (Ch), respectively. The voltage for both capsules types was fixed at 1.35 kV. Then, the capsules were incubated in a simulated gastrointestinal (GI) system for 6 hr at 37 °C. The addition of PEG in a CaCl2 hardening solution led to degradation of the Ch capsule (Ch-PEG) and the release of cells into the small intestine vessel in the simulated GI system. By contrast, the cells were trapped within the Al capsules. Based on these data, effective encapsulation using alginate with CREP and PEG can enable JW15 to be released at a targeted anatomical site of activity within the GI system, thereby, enhancing the efficacy of probiotic cells. These protective effects can be leveraged during the development of probiotic products. PRACTICAL APPLICATION: Weissella cibaria JW15 (109 cells/mL) was encapsulated in biodegradable and biocompatible capsules, prepared by mixing 1.5% alginate with 1% chicory root extract powder (CREP) in 0.1 M CaCl2 and 0.05% PEG using an encapsulator. The optimal processing parameters were as follows: pressure, 100 mbar; vibration frequency, 350 Hz; voltage, 1.35 kV; and core flow rate, 2 mL/min. When the resulting capsules were subjected to a simulated gastrointestinal system for 6 hr, the cells were released into the small intestine, and up to 95% cell viability was preserved. These results suggest that capsules made from alginate with CREP and formulated using calcium and PEG are a promising delivery system for probiotic cells.


Asunto(s)
Alginatos/química , Achicoria/química , Composición de Medicamentos/métodos , Extractos Vegetales/química , Probióticos/química , Weissella/química , Cápsulas/química , Cápsulas/metabolismo , Tracto Gastrointestinal/metabolismo , Humanos , Viabilidad Microbiana , Modelos Biológicos , Raíces de Plantas/química , Probióticos/metabolismo
7.
Pharm Res ; 37(3): 39, 2020 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-31965330

RESUMEN

PURPOSE: The intratumoral heterogeneity observed in breast cancer (BC), in particular with regard to cell surface receptor expression, can hinder the success of many targeted cancer therapies. The development of novel therapeutic agents that target more than one receptor can overcome this inherent property of tumors and can facilitate their selective internalization in cancer cells. The goal of this study is to develop a drug combination-loaded nanoparticle (NP) formulation that is actively-targeted to HER2 and EGFR receptors on BC cells. METHODS: A polymeric NP formulation was prepared which co-encapsulated a synergistic combination of the chemotherapeutic agent, paclitaxel (PTX), and the mTOR inhibitor, everolimus (EVER), and is targeted to HER2 and EGFR receptors on BC cells using antibody Fab fragments as the targeting moieties. The physicochemical characteristics of the dual-targeted formulation (Dual-NP) were evaluated, along with its cytotoxic profile (in both, monolayer and 3D BC models), as well as the degree of cellular uptake in HER2high/EGFRmod and HER2neg/EGFRlow BC cells. RESULTS: Dual-NPs were found to have significantly higher cytotoxicity relative to HER2 mono-targeted (T-NPs) and untargeted NPs (UT-NPs) in HER2high/EGFRmod monolayer BC cells after 72 h exposure, while no significant difference was observed in HER2neg/EGFRlow cells. However, in the HER2high/EGFRmod spheroids, the cytotoxicity of Dual-NPs was comparable to that of T-NPs. This was thought to be attributed to the previously reported downregulation of EGFR in 3D in comparison to 2D BC models. Dual-NPs had significantly higher cellular uptake relative to UT-NPs and T-NPs in HER2high/EGFRmod BC cells after 24 h exposure, whereas in the HER2neg/EGFRlow cells, the increase in cellular uptake of the Dual-NPs was not as high as the level achieved in the HER2high/EGFRmod cells. Blocking HER2 and EGFR significantly reduced the uptake of T-NPs and Dual-NPs in the HER2high/EGFRmod BC cells, demonstrating specific binding to both EGFR and HER2. CONCLUSIONS: The dual-targeting strategy developed in this study in conjunction with a potentially promising delivery vector for a synergistic combination therapy can overcome receptor heterogeneity, yielding significant improvements in the cytotoxicity and cellular uptake in BC cells.


Asunto(s)
Antineoplásicos/química , Neoplasias de la Mama/tratamiento farmacológico , Everolimus/química , Nanocápsulas/química , Paclitaxel/química , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Línea Celular Tumoral , Supervivencia Celular , Composición de Medicamentos/métodos , Liberación de Fármacos , Receptores ErbB/metabolismo , Everolimus/farmacología , Femenino , Humanos , Terapia Molecular Dirigida/métodos , Paclitaxel/farmacología , Panitumumab/química , Panitumumab/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Receptor ErbB-2/metabolismo , Propiedades de Superficie , Trastuzumab/química , Trastuzumab/metabolismo
8.
Pharm Res ; 37(3): 36, 2020 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-31965346

RESUMEN

PURPOSE: We describe the preparation of injectable polymeric paste (IPP) formulations for local and sustained release of drugs. Furthermore, we include the characterization and possible applications of such pastes. Particular attention is paid to characteristics relevant to the successful clinical formulation development, such as viscosity, injectability, degradation, drug release, sterilization, stability performance and pharmacokinetics. METHODS: Paste injectability was characterized using measured viscosity and the Hagen-Poiseuille equation to determine injection forces. Drug degradation, release and formulation stability experiments were performed in vitro and drug levels were quantified using HPLC-UV methods. Pharmacokinetic evaluation of sustained-release lidocaine IPPs used five groups of six rats receiving increasing doses subcutaneously. An anti-cancer formulation was evaluated in a subcutaneous tumor xenograft mouse model. RESULTS: The viscosity and injectability of IPPs could be controlled by changing the polymeric composition. IPPs demonstrated good long-term stability and tunable drug-release with low systemic exposure in vivo in rats. Preliminary data in a subcutaneous tumor model points to a sustained anticancer effect. CONCLUSIONS: These IPPs are tunable platforms for local and sustained delivery of drugs and have potential for further clinical development to treat a number of diseases.


Asunto(s)
Portadores de Fármacos/química , Composición de Medicamentos/métodos , Pomadas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Anilidas/química , Anilidas/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Docetaxel/química , Docetaxel/farmacología , Liberación de Fármacos , Estabilidad de Medicamentos , Humanos , Inyecciones , Lidocaína/química , Lidocaína/farmacocinética , Masculino , Ratones , Ratones Desnudos , Neoplasias Experimentales , Nitrilos/química , Nitrilos/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Ratas , Compuestos de Tosilo/química , Compuestos de Tosilo/farmacología , Viscosidad
9.
Pharm Res ; 37(3): 34, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31942651

RESUMEN

PURPOSE: Alzheimer's disease is a neurodegenerative disorder, and most common form of dementia afflicting over 35 million people worldwide. Rivastigmine is a widely used therapeutic for ameliorating clinical manifestations of Alzheimer's disease. However, current treatments require frequent dosing either orally or via transdermal patch that lead to compliance issues and administration errors risking serious adverse effects. Our objective was to develop a smart polymer based delivery system for controlled release of rivastigmine over an extended period following a single subcutaneous injection. METHODS: Rivastigmine release was optimized by tailoring critical factors including polymer concentration, polymer composition, drug concentration, solvent composition, and drug hydrophobicity (rivastigmine tartrate vs base). Optimized in vitro formulation was evaluated in vivo for safety and efficacy. RESULTS: Formulation prepared using PLGA (50:50) at 5% w/v in 95:5 benzyl benzoate: benzoic acid demonstrated desirable controlled drug release characteristics in vitro. The formulation demonstrated sustained release of rivastigmine tartrate for 7 days in vivo with promising biocompatibility and acetylcholinesterase inhibition efficacy for 14 days. CONCLUSION: The results exemplify an easily injectable controlled release formulation of rivastigmine prepared using phase-sensitive smart polymer. The optimized formulation significantly increases the dosing interval, and can potentially improve patient compliance as well as quality of life of patients living with Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/química , Portadores de Fármacos/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Rivastigmina/química , Polímeros de Estímulo Receptivo/química , Inhibidores de la Colinesterasa/administración & dosificación , Composición de Medicamentos/métodos , Liberación de Fármacos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Transición de Fase , Rivastigmina/administración & dosificación , Solventes/química
10.
Chemistry ; 26(11): 2470-2477, 2020 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-31912555

RESUMEN

Multidrug resistance (MDR) is regarded as a main obstacle for effective chemotherapy, and P-glycoprotein (P-gp)-mediated drug efflux has been demonstrated to be the key factor responsible for MDR. In this study, a novel pH-responsive hybrid drug delivery system was developed by conjugating d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), a kind of P-gp inhibitor, on the surface of laponite nanodisks to overcome MDR. The prepared LM-TPGS display excellent colloidal stability, a high encapsulation efficiency of doxorubicin (DOX), and a pH-responsive drug release profile. In vitro experiments verified that LM-TPGS/DOX could exhibit significantly enhanced therapeutic efficacy in treating DOX-resistant breast cancer cells (MCF-7/ADR) through inhibiting the activity of P-gp-mediated drug efflux and effectively accumulating DOX within cancer cells. In vivo results revealed that LM-TPGS/DOX outstandingly suppressed MCF-7/ADR tumors with low side effects. Therefore, the high drug payload, enhanced inhibition efficacy to drug-resistant cells, and low side effects make the LM-TPGS/DOX a promising nanoplatform to reverse MDR for effective chemotherapy.


Asunto(s)
Antibióticos Antineoplásicos/química , Doxorrubicina/química , Nanocápsulas/química , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antibióticos Antineoplásicos/farmacología , Doxorrubicina/farmacología , Composición de Medicamentos/métodos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Polietilenglicoles/química , Polietilenglicoles/metabolismo , Vitamina E/química , Vitamina E/metabolismo
11.
AAPS PharmSciTech ; 21(2): 40, 2020 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-31897805

RESUMEN

There is a need to develop in vitro dissolution methods that discriminate for particle size of the manipulated abuse deterrent formulation (ADF) and that can be used for in vivo predictive models since dissolution methods developed for intact formulation might not be suitable for manipulated ones. A vertical diffusion cell (VDC) and United States Pharmacopeia (USP) Apparatus 1, 2, and 4 were evaluated for measuring the dissolution of intact and manipulated metoprolol succinate tablets with abuse deterrent-like properties. These tablets were physically manipulated to produce fine (106-500 µm) and coarse (500-1000 µm) powder samples. The VDC method was not able to discriminate the effect of particle size on drug release with varied stirring rate (200 to 800 rpm), molecular weight cut-off (MWCO, 3-5 kDa to 12-14 kDa) of the diffusion membrane, or composition and ionic strength (0.45% and 0.9%) of receiver medium. Standard and modified USP Apparatus 1 and 2 methods were assessed; however, large variations (RSD > 20%) were observed with USP Apparatus 1 for manipulated product dissolution and floating powder samples caused failure of auto-sampling when using standard USP Apparatus 2. For the USP Apparatus 4 dissolution method, packing configuration (1, 3, 8 layers and blend), ionic strength of dissolution medium (0.017, 0.077, and 0.154 M additional NaCl), and flow rate (4, 8, 16 mL/min) were studied to discriminate the effect of particle size on release. The USP Apparatus 4 dissolution method was optimized by using a packaging configuration of 8 layers with 8 mL/min flow rate which exhibited low variability and complete drug release and it could be used for in vivo predictive models. The dissolution method variables can be optimized for a specific product for desirable reproducibility and discriminatory power when using USP Apparatus 4.


Asunto(s)
Formulaciones Disuasorias del Abuso , Composición de Medicamentos/métodos , Liberación de Fármacos , Mal Uso de Medicamentos de Venta con Receta/prevención & control , Difusión , Metoprolol/administración & dosificación , Metoprolol/química , Modelos Teóricos , Peso Molecular , Tamaño de la Partícula , Polvos , Solubilidad , Comprimidos
12.
J Agric Food Chem ; 68(5): 1198-1206, 2020 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-31928001

RESUMEN

In this study, three types of pyraclostrobin formulations (including emulsifiable concentrate (EC), suspension concentrate (SC), and microcapsules (MCs)) were used to control cucumber anthracnose. Pyraclostrobin EC had the highest inhibitory activity against Colletotrichum orbiculare in vitro. Much different from the bioactivity in vitro, pyraclostrobin MCs exhibited the highest control efficacy on cucumber anthracnose both in pot and field experiments. The physicochemical properties (particle size, surface tension) of the spray dilution, their interaction with target leaves (contact angle, adhesional tension, work of adhesion, retention, crystallization) and dissipation dynamic of the active ingredient were found to be highly potential factors that would significantly influence the control efficacy of pesticide formulations. Results showed that the control efficacies of different formulations of pyraclostrobin were determined mainly by the final behavior of the pesticides at the target interface, namely, the retention, crystallization, and dissipation dynamics of active ingredients. This study had revealed crucial factors that would influence the efficacy of different formulations of pyraclostrobin and thus could guide the rational and efficient use of different formulations of pesticides on target crops.


Asunto(s)
Colletotrichum/efectos de los fármacos , Cucumis sativus/microbiología , Composición de Medicamentos/métodos , Fungicidas Industriales/química , Fungicidas Industriales/farmacología , Enfermedades de las Plantas/microbiología , Estrobilurinas/química , Estrobilurinas/farmacología , Colletotrichum/fisiología , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/microbiología
13.
Crit Rev Anal Chem ; 50(1): 62-77, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30810335

RESUMEN

Piperine (PIP) is a natural alkaloid isolated from Piper longum L. that presents antioxidant, anticonvulsant, antimicrobial, neuroprotective, larvicidal, antiparasitic, anticancer effect and other pharmacological properties. However, the low aqueous solubility is the main barrier to its development from the laboratory to the clinic as a drug. Several strategies have been used to overcome this obstacle, like the incorporation of PIP into different drug delivery systems turned out to be highly efficient. In addition, several methods for the quantitative and qualitative analysis of PIP in various raw materials, including biological fluids (plasma, urine, metabolites, brain), plants and drug delivery systems, were investigated. Most recently high-performance liquid chromatography was used together with several detectors for this purpose. Therefore, this review presents a summary of characteristics chemical and biological properties of PIP as well as several techniques and analytical methods to optimize the analytical signal, increase sensitivity, selectivity and reduce the effects of interference for this drug.


Asunto(s)
Alcaloides/análisis , Benzodioxoles/análisis , Portadores de Fármacos/química , Piperidinas/análisis , Alcamidas Poliinsaturadas/análisis , Disponibilidad Biológica , Encéfalo/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Composición de Medicamentos/métodos , Liberación de Fármacos , Humanos , Solubilidad , Espectrometría de Masas en Tándem/métodos , Agua
14.
Crit Rev Anal Chem ; 50(1): 90-96, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30942085

RESUMEN

Tazarotene (TZR) is the first topical receptor-selective retinoid prodrug derived from vitamin A used for management of plaque psoriasis and efficacious in dealing of acne vulgaris, and photo aging. As per US food and drug administration (FDA), 0.1% strength of TZR is permitted for the treatment of acne. This article draws attention to various advanced and conventional analytical methods. The hyphenated and conventional chromatographic techniques such as LC-MS/MS and HPTLC, HPLC respectively. Moreover, spectrophotometric methods like UV/visible spectroscopy also used to quantify TZR as active pharmaceutical ingredient and its formulations, especially in topical preparations. Moreover, the TZR is required alternative methods for routine quality control and to estimate TZR in pharmaceutical dosage form especially in pharmacokinetic studies of topical preparation. This write up focus on critical review of characteristics, uses and the information about the physicochemical, pharmacokinetics properties, mechanisms of action and more emphasis on different analytical methods for estimation of TZR in pharmaceutical formulations.


Asunto(s)
Ácidos Nicotínicos/análisis , Profármacos/análisis , Administración Tópica , Cromatografía Líquida de Alta Presión , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Tecnología Química Verde/métodos , Humanos , Ácidos Nicotínicos/farmacocinética , Espectrofotometría Ultravioleta , Espectrometría de Masas en Tándem
15.
Appl Biochem Biotechnol ; 190(1): 182-196, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31313242

RESUMEN

The present study aimed to improve the survivability of L. acidophilus encapsulated in alginate-whey protein isolate (AL-WPI) biocomposite under simulated gastric juice (SGJ) and simulated intestinal juice (SIJ). Microcapsules were prepared based on emulsification/internal gelation technique. Optimal compositions of AL and WPI and their ratio in the aqueous phase were evaluated based on minimizing mean diameter (MD) of the microcapsules and maximizing encapsulation efficiency (EE), survivability of cells under SGJ (Viability), and release of viable cells under SIJ (Release) using Box-Behnken experimental design. Optimal composition comprising 4.54% (w/v) AL, 10% (w/v) WPI, and 10% (v/v) AL-WPI gum in the aqueous phase was determined statistically. Physicochemical characteristics of the optimized matrix were investigated by SEM, FTIR, and XRD analysis to determine surface morphology, molecular bonds, and crystalline nature of such hydrocolloid. It could be concluded that the proposed biocomposite is a good promise for nutrients encapsulation in the food industry.


Asunto(s)
Alginatos/química , Cápsulas , Lactobacillus acidophilus/fisiología , Probióticos , Proteína de Suero de Leche/química , Recuento de Colonia Microbiana , Composición de Medicamentos/métodos , Lactobacillus acidophilus/aislamiento & purificación
16.
J Agric Food Chem ; 68(1): 97-105, 2020 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-31830779

RESUMEN

The oral delivery efficiency of aged citrus peel extract containing polymethoxyflavones and 5-demethylated polymethoxyflavones (PMFs) in three different systems, including a pure oil phase, a Tween 80-stabilized nanoemulsion, and a milled-cellulose-particles-stabilized Pickering emulsion, was investigated using two typical in vitro digestion models. The digestion profiles and release of PMFs in these emulsions and bulk oil in the human upper gastrointestinal (GI) tract were evaluated using the pH-stat lipolysis model and TNO's gastrointestinal model (TIM-1). Compared to the bulk oil sample, the bioaccessibilities of PMFs in the nanoemulsion and Pickering emulsion were both increased by around 14 fold when the pH-stat lipolysis model was used. However, the results from the TIM-1 system indicated that the bioaccessibilities of PMFs in the nanoemulsion and Pickering emulsion were around two and four times that in bulk oil, respectively. The results from this work would provide valuable information for the rational design and evaluation of lipid-based delivery systems for lipophilic bioactive compounds.


Asunto(s)
Citrus/metabolismo , Composición de Medicamentos/métodos , Lípidos/química , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Citrus/química , Digestión , Emulsiones/química , Flavonas/química , Flavonas/metabolismo , Frutas/química , Frutas/metabolismo , Tracto Gastrointestinal , Humanos , Modelos Biológicos , Tamaño de la Partícula
17.
Mater Sci Eng C Mater Biol Appl ; 106: 110184, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31753394

RESUMEN

There is an increasing attention on solid lipid nanoparticles (SLNs) due to their high biocompatibility and ability to enhance bioavailability for poorly water-soluble drugs. Preparation of SLNs that are capable of high drug loading and sustained drug release through hot melt sonication method is reported here. SLNs of palmitic acid and stearic acid loaded with poorly water-soluble drugs, viz. fenofibrate (FF) and nabumetone (NBT) having spherical morphology and average particle size below 200 nm were prepared. Poloxamer 407 and pluronic® F-127 were used as surfactants. Particle size and spherical morphology was confirmed by dynamic light scattering, field emission scanning electron microscopy, transmission electron microscopy, and atomic force microscopy. The chemical, crystal, and thermal properties of SLNs were studied by Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry, respectively. The palmitic acid-poloxamer 407 SLNs could entrap upto 13.8% FF with 80% entrapment efficiency while the stearic acid-pluronic® F-127 SLNs entrapped 13.6% NBT with 89% entrapment efficiency. The drug loaded in SLNs showed controlled release up to 3 days as confirmed by in-vitro drug release profile. Moreover, the drug loaded SLNs did not show any toxicity on macrophage cell line proving the use of these formulations as control drug delivery vehicles for the studied drugs.


Asunto(s)
Fenofibrato/química , Lípidos/química , Nabumetona/química , Nanopartículas/química , Rastreo Diferencial de Calorimetría , Preparaciones de Acción Retardada/química , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Ácidos Esteáricos/química
18.
Carbohydr Polym ; 228: 115398, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31635734

RESUMEN

In this study, amphiphilic conjugates were synthesized by conjugating curcumin (CUR) to a food-derived hydrophilic hydroxyethyl starch (HES) via an acid-labile ester linker. The self-assembly of the conjugates formed uniform micellar nanoparticles (HES-CUR NPs) with a desirable drug loading efficiency, excellent colloidal and storage stability, as well as acid-responsive release manner. Besides, the formation of the nanoparticles increased the solubility of CUR to thousands times higher than free CUR, and effectively protected the loaded CUR from degradation upon exposure to UV light and high temperature. In vitro cytotoxicity assay and radical scavenging experiments demonstrated that the HES-CUR NPs significantly improved the cytocompatibility, anticancer and antioxidant activity of CUR due to the enhanced solubility, stability, and bioavailability. The HES-CUR NPs reported herein have a great potential in developing functional food or pharmaceutical formulations for preventing or treating various diseases such as inflammatory diseases and cancer.


Asunto(s)
Curcumina/farmacología , Portadores de Fármacos/química , Nanopartículas/uso terapéutico , Almidón/química , Antineoplásicos/farmacología , Antioxidantes/farmacología , Células CACO-2 , Composición de Medicamentos/métodos , Liberación de Fármacos , Células HeLa , Humanos , Micelas , Neoplasias/tratamiento farmacológico , Solubilidad
19.
J Pharm Biomed Anal ; 177: 112846, 2020 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-31522097

RESUMEN

The ß-lactam core is a key structure responsible for inducing both IgE-mediated acute-onset hypersensitivity and T-cell-mediated delayed-onset hypersensitivity with penicillins in humans. There is essentially no clinically significant immunologic cross-reactivity noted between the ß-lactam cores of penicillins and cephalosporins based on challenge studies in humans. The side-chains appear to be more important in inducing IgE-mediated acute-onset hypersensitivity and T-cell delayed-onset hypersensitivity with cephalosporins in humans. Despite these clinical findings, the U. S. Food and Drug Administration (FDA) still requires the level of ß-lactam-related antibiotic residues to be controlled at very low levels in manufacturing facilities. Ceftolozane is Merck & Co., Inc., Kenilworth, NJ, USA's (MSD's) 5th generation broad spectrum cephalosporin antibiotic against gram-negative bacteria. In searching for the optimal decontamination method of ceftolozane, most methods were found to be very slow in opening the ß-lactam ring in ceftolozane. Moreover, most of the previously reported decontamination methods applied analytical methods that only monitored the disappearance of the parent molecule as the endpoint of degradation. In this way, many of the ß-lactam-containing degradation products could be overlooked. In order to develop an efficient decontamination solution for ceftolozane, a sensitive ultra high performance liquid chromatography-high resolution-electrospray ionization-tandem mass spectrometry (UHPLC-HRMS/MS) method was first developed to ensure the detection of the ß-lactam ring in all degradation products. Through online UHPLC-UV-HRMS monitoring, 2.5 N KOH in 50% aqueous MeOH or 50% aqueous EtOH was identified as the best condition to fully degrade the ß-lactam ring in ceftolozane. This decontamination could be done within 15 min, even at 100 mg/mL concentration, and thus enable a quick turnaround time for equipment cleaning in the ß-lactam manufacturing facility. This method was also successfully applied to 12 other commercially available ß-lactam antibiotics.


Asunto(s)
Antibacterianos/análisis , Cefalosporinas/análisis , Descontaminación/métodos , Composición de Medicamentos/instrumentación , Contaminación de Equipos/prevención & control , Antibacterianos/química , Antibacterianos/toxicidad , Cefalosporinas/química , Cefalosporinas/toxicidad , Cromatografía Líquida de Alta Presión/métodos , Composición de Medicamentos/métodos , Composición de Medicamentos/normas , Etanol/química , Hidróxidos/química , Metanol/química , Compuestos de Potasio/química , Solventes/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos
20.
J Pharm Biomed Anal ; 177: 112886, 2020 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-31563757

RESUMEN

The performance of transmission Raman spectroscopy (TRS) for quantifying a cocrystal and its dissociation in solid dosage form was investigated. Some tablets containing 0%-20% (w/w) of a cocrystal of carbamazepine (CBZ)/succinic acid (SUC), 0%-4% of CBZ, 0%-4% of SUC, and 75%-99% of D-mannitol were prepared. The Raman spectra of these tablets were preprocessed using the standard normal variate (SNV) or multiplicative scatter correction (MSC) as well as the Savitzky Golay second derivative, and then, these were used to generate calibration models using partial least squares (PLS) regression. The performance of the model was superior when the MSC preprocessing spectra of the cocrystal between 200 and 1800 cm-1 were used for calibration. The determination coefficient of the PLS calibration curve for the CBZ/SUC cocrystal between 200 and 1800 cm-1 with MSC was 0.97, root mean square error of cross validation (RMSECV) was 1.16, and root mean square error of prediction (RMSEP) was 1.10. As in the case of the CBZ/SUC cocrystal, the performance of the model was superior when the MSC preprocessing spectra of CBZ and SUC between 200 and 1800 cm-1 were used for calibration. These data suggest that TRS is useful for quantifying a cocrystal and its dissociation compounds in solid dosage forms.


Asunto(s)
Carbamazepina/química , Composición de Medicamentos/métodos , Espectrometría Raman/métodos , Ácido Succínico/química , Disponibilidad Biológica , Calibración , Carbamazepina/farmacocinética , Química Farmacéutica/métodos , Cristalización , Estudios de Factibilidad , Análisis de los Mínimos Cuadrados , Ácido Succínico/farmacocinética , Comprimidos
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