Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.249
Filtrar
1.
Anticancer Res ; 40(9): 5097-5106, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878798

RESUMO

BACKGROUND/AIM: Accumulating evidence has shown therapeutic effects of herbals on breast cancer, a commonly diagnosed malignancy in women worldwide. However, their underlying mechanisms remain unclear. We aimed to explore the mode of action of a recently developed herbal combination at system-level. MATERIALS AND METHODS: We employed network pharmacological approaches to study the mechanism of a combination of three herbals, Astragalus membranaceus, Angelica gigas and Trichosanthes kirilowii by investigating active compounds and performing functional enrichment analysis for the interacting targets. RESULTS: For in silico pharmacokinetic evaluation, ten active ingredients interacted with fifty-six breast cancer-associated therapeutic targets. Functional enrichment analysis revealed that TNF, estrogen, PI3K-Akt and MAPK signaling pathways were involved in tumorigenesis and development of breast cancer. The pharmacological mechanisms might be associated with cellular effects on proliferation, cell cycle process and apoptosis. CONCLUSION: The present study provides novel insights into the system-level pharmacological mechanisms underlying a herbal combination used for breast cancer therapies.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Redes Neurais de Computação , Biologia de Sistemas/métodos , Tecnologia Farmacêutica/métodos , Antineoplásicos Fitogênicos/química , Astragalus propinquus , Neoplasias da Mama , Linhagem Celular Tumoral , Biologia Computacional/métodos , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Feminino , Humanos , Medicina Tradicional Chinesa , Fluxo de Trabalho
2.
AAPS PharmSciTech ; 21(5): 179, 2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32596747

RESUMO

Coating process is a critical unit operation for manufacturing solid oral dosage forms. For a long time, the coating weight gain has been discerned as the most important, if not only, characteristic describing the coating quality. As the introduction of quality by design (QbD) and advancement of process analytical technology (PAT), nowadays more techniques are available to analyze other quality attributes which have been overlooked but have substantial impacts on the performance of coated products. The techniques that permit rapid and non-destructive measurements are of particular importance to improve process operation and product quality. This article reviews the analytical techniques that have been and potentially could be used as PAT tools for characterizing the quality of pharmaceutical coating product. By identifying the challenges and pitfalls encountered during PAT application, the review aims at fostering the adoption of PAT for paving the way to enhanced quality and efficiency of the coating processes.


Assuntos
Tecnologia Farmacêutica/métodos , Preparações Farmacêuticas , Análise Espectral/métodos
3.
An Acad Bras Cienc ; 92(1): e20181021, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401841

RESUMO

Fosamprenavir calcium is an amprenavir prodrug of the protease inhibitors class used in the treatment of patients with acquired immunodeficiency syndrome (AIDS). Different solid forms of this drug are described in patents, in this sense studies on the physico-chemical characterization and stability are relevant for the selection of a solid form with adequate features for pharmaceutical purposes. In the present work form I (commercial) and amorphous of fosamprenavir calcium were characterized by the techniques of Differential Scanning Calorimetry (DSC), Thermogravimetry (TGA), Powder X-ray Diffraction (PXRD), Fourier-Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). Furthermore, the chemical and polymorphic stability of the commercial form were evaluated by DSC, PXRD, FTIR and High-Performance Liquid Chromatography (HPLC). In the studies of characterization, thermal analyses allied to spectroscopic methods (PXRD and FTIR) demonstrated that the presence of water in the crystalline structure of Form I is fundamental for maintaining its crystallinity. In studies of accelerated stability the techniques of DSC, PXRD and FTIR showed that Form I does not suffer phase change when submitted to controlled conditions of temperature and humidity. Moreover, HPLC and FTIR proved the chemical stability of this solid form of fosamprenavir, thus demonstrating its suitability for pharmaceutical purposes.


Assuntos
Carbamatos/química , Organofosfatos/química , Preparações Farmacêuticas/análise , Sulfonamidas/química , Tecnologia Farmacêutica/métodos , Umidade , Microscopia Eletrônica de Varredura , Análise Espectral/métodos , Temperatura , Termodinâmica
4.
Expert Opin Drug Deliv ; 17(7): 899-902, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32427004

RESUMO

The ongoing COVID-19 crisis has highlighted the importance of a robust drug supply chain which can be quickly and flexibly ramped up to produce life-saving drug treatments. 3D printing (3DP) of oral solid dosage forms (OSDF) could be a viable part of the emergency drug production response to support vulnerable patients in rural regions and other isolated locations. In the context of the current pandemic, the suitability of different 3DP technologies will depend on the physicochemical properties, unit dose strength and BCS classification of the repurposed drug compounds currently being trialed for COVID-19. Furthermore, the deployment strategy should focus on simplifying dosage forms and formulations, scaling down the size and complexity of the printing systems and real-time quality assurance via process analytical technologies (PAT).


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Química Farmacêutica/métodos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Impressão Tridimensional , Administração Oral , Humanos , Pandemias , Tecnologia Farmacêutica/métodos
5.
Pharm Res ; 37(5): 90, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382838

RESUMO

PURPOSE: The blood-brain barrier limits the application of idarubicin in the therapy of glioblastoma multiforme. Biodegradable, intracranial wafers with prolonged release may increase therapy efficiency. METHODS: Blank wafers, wafers containing 5% w/w and 10% w/w of idarubicin were formulated by solution casting from poly(L-lactide-co-glycolide) and poly(glycolide-co-ε-caprolactone). The following methods were used: NMR, GPC, DSC, FTIR, AFM, UV-VIS, and a viability and proliferation assay for idarubicin action (U87MG cell line). RESULTS: Wafers showed a surface with numerous immersions and hills. A lack of interactions between idarubicin and the copolymers was observed. The substance was entrapped in the matrix and released in two phases for all wafers with the appropriate bolus and maintenance dose. The burst effect was observed for all wafers, however, the biggest bolus for poly(L-lactide-co-glycolide) wafers containing 5% w/w of idarubicin was noted. The stable and steady degradation of poly(glycolide-co-ε-caprolactone) wafers containing 5% w/w of idarubicin ensures the most optimal release profile and high inhibition of proliferation. CONCLUSIONS: Copolymer wafers with idarubicin are an interesting proposition with great potential for the local treatment of glioblastoma multiforme. The release rate and dose may be regulated by the amount and kind of wafers for various effects.


Assuntos
Portadores de Fármacos/síntese química , Glioblastoma/tratamento farmacológico , Idarubicina/uso terapêutico , Polímeros/síntese química , Linhagem Celular Tumoral , Sobrevivência Celular , Liberação Controlada de Fármacos , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Tecnologia Farmacêutica/métodos
6.
Anesth Analg ; 130(5): 1120-1132, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32287120

RESUMO

As most of us are aware, almost every facet of our society is becoming, for better or worse, progressively more technology-dependent. Technological advancement has made autonomous systems, also known as robots, an integral part of our life in several fields, including medicine. The application of robots in anesthesia could be classified into 3 types of robots. The first ones are pharmacological robots. These robots are based on closed-loop systems that allow better-individualized anesthetic drug titration for optimal homeostasis during general anesthesia and sedation. Recent evidence also demonstrates that autonomous systems could control hemodynamic parameters proficiently outperforming manual control in the operating room. The second type of robot is mechanical. They enable automated motorized reproduction of tasks requiring high manual dexterity level. Such robots have been advocated to be more accurate than humans and, thus, could be safer for the patient. The third type is a cognitive robot also known as decision support system. This type of robot is able to recognize crucial clinical situation that requires human intervention. When these events occur, the system notifies the attending clinician, describes relevant related clinical observations, proposes pertinent therapeutic options and, when allowed by the attending clinician, may even administer treatment. It seems that cognitive robots could increase patients' safety. Robots in anesthesia offer not only the possibility to free the attending clinicians from repetitive tasks but can also reduce mental workload allowing them to focus on tasks that require human intelligence such as analytical and clinical approach, lifesaving decision-making capacity, and interpersonal interaction. Nevertheless, further studies have yet to be done to test the combination of these 3 types of robots to maintain simultaneously the homeostasis of multiple biological variables and to test the safety of such combination on a large-scale population.


Assuntos
Anestesia/métodos , Robótica/métodos , Anestesia/tendências , Humanos , Robótica/tendências , Tecnologia Farmacêutica/métodos , Tecnologia Farmacêutica/tendências
7.
Pharm Res ; 37(5): 84, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32318827

RESUMO

PURPOSE: The current trend for continuous drug product manufacturing requires new, affordable process analytical techniques (PAT) to ensure control of processing. This work evaluates whether property models based on spectral data from recent Fabry-Pérot Interferometer based NIR sensors can generate a high-resolution moisture signal suitable for process control. METHODS: Spectral data and offline moisture content were recorded for 14 fluid bed dryer batches of pharmaceutical granules. A PLS moisture model was constructed resulting in a high resolution moisture signal, used to demonstrate (i) endpoint determination and (ii) evaluation of mass transfer performance. RESULTS: The sensors appear robust with respect to vibration and ambient temperature changes, and the accuracy of water content predictions (±13 % ) is similar to those reported for high specification NIR sensors. Fusion of temperature and moisture content signal allowed monitoring of water transport rates in the fluidised bed and highlighted the importance water transport within the solid phase at low moisture levels. The NIR data was also successfully used with PCA-based MSPC models for endpoint detection. CONCLUSIONS: The spectral quality of the small form factor NIR sensor and its robustness is clearly sufficient for the construction and application of PLS models as well as PCA-based MSPC moisture models. The resulting high resolution moisture content signal was successfully used for endpoint detection and monitoring the mass transfer rate.


Assuntos
Espectroscopia de Luz Próxima ao Infravermelho/economia , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação , Tecnologia Farmacêutica/métodos , Composição de Medicamentos , Sistemas Microeletromecânicos , Pós/química , Pressão , Temperatura , Água
8.
AAPS PharmSciTech ; 21(4): 119, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32318974

RESUMO

In the presented study, insight into the development and optimisation of the dry emulsion formulation and spray drying process is provided. The aim was to facilitate the dissolution of the poorly soluble, highly lipophilic drug, simvastatin, by forming spray-dried dry emulsion particles having adequate powder flow properties, while assuring sufficient drug content. Simvastatin and a mixture of caprylic, capric triglyceride and 1-oleoyl-rac-glycerol were employed as a model drug and solubilising oils, respectively. A matrix of the dry emulsions was composed at a fixed ratio mixture of mannitol and HPMC. Tween 20 was used in low amounts as the primary emulsion stabiliser. To facilitate process optimisation, a DoE surface response design was used to study the influence of formulation and process parameters on the particle size distribution, powder bulk properties, emulsion reconstitution ability, drug stability and process yield of spray-dried products. Two-fluid nozzle geometry was identified, studied and confirmed to be important for most product critical quality attributes. Models obtained after the study showed acceptable coefficients of determination and provided good insight in the relationship governing the process and product characteristics. Five model optimised products showed adequate process yield, suitable particle size distribution, good reconstitution ability and improved dissolution profile, when compared to a non-lipid-based tablet and the pure drug. However, the obtained dry emulsion powders exhibited poor flow character according to the Carr index. The optimised product was further analysed with NMR during lipolysis to gain insight into the species formed during digestion and the kinetics of their formation.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Emulsões/síntese química , Sinvastatina/síntese química , Tecnologia Farmacêutica/métodos , Fenômenos Químicos , Dessecação/métodos , Estabilidade de Medicamentos , Emulsões/administração & dosagem , Glicerídeos/administração & dosagem , Glicerídeos/síntese química , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/síntese química , Tamanho da Partícula , Polissorbatos/administração & dosagem , Polissorbatos/síntese química , Sinvastatina/administração & dosagem , Solubilidade , Comprimidos
9.
PLoS Negl Trop Dis ; 14(3): e0008142, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32210437

RESUMO

Human rabies, a neglected viral zoonosis, is preventable through domestic animals vaccination and post-exposure prophylaxis using inactivated rabies vaccines. During vaccine production, several mandatory in vivo quality control trials, such as potency, live virus, and safety, are responsible for the use of large numbers of laboratory animals. Over the years, global organizations encouraged the development of alternative methods to reduce, replace and refine the use of animals in the pharmaceutical industry. In this study we standardized an in vitro assay for determination of residual live virus combining viral isolation techniques with direct immunofluorescence detection and viral quantification by a molecular method. Standardization of viral recovery steps and quantification by RT-qPCR were performed and the combined method was shown to be 3 fold more sensitive than the in vivo assay. It was possible to identify viral suspensions cultures, which still had residual viable rabies virus particles, evidencing the importance to implement this method in quality control schemes of rabies vaccine production. In addition, this developed assay is more practical, inexpensive and less time consuming, producing results in just 4 days, which may allow greater agility in the internal quality control of the vaccine. The in vitro method may reduce 2/3rd of laboratory animals numbers used for this purpose, since it can be applied in the intermediate quality control of inactivated rabies vaccine production.


Assuntos
Vacinas Antirrábicas/normas , Vírus da Raiva/crescimento & desenvolvimento , Vírus da Raiva/isolamento & purificação , Tecnologia Farmacêutica/métodos , Tecnologia Farmacêutica/normas , Cultura de Vírus/métodos , Técnica Direta de Fluorescência para Anticorpo , Reação em Cadeia da Polimerase em Tempo Real , Vacinas de Produtos Inativados/normas
10.
J Chromatogr A ; 1619: 460911, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32007219

RESUMO

High performance liquid chromatography (HPLC) methods with UV/vis detection are the most widespread analytical procedures in modern pharmaceutical applications, but reach their limitations when it comes to non-chromophore molecules. Hence, instead of using tiresome derivatization procedures, many liquid chromatography methods make use of the so-called aerosol-based universal detectors, namely the evaporative light scattering detector (ELSD), the condensation nucleation light scattering detector (CNLSD) and the charged aerosol detector (CAD). Amongst these, the CAD, being the youngest (introduced in 2005) of these three options, is often described as the most easy-to-use detector and is stated to exhibit sufficient sensitivity and good linearity of signal in a dedicated range of concentration. Therefore, this review sets its focus on the recent applications of the CAD for active pharmaceutical ingredients, excipient analysis as well as botanical applications. Alongside the post-column solvent addition techniques, the new CAD's ability to adjust the evaporation temperature and the possibility to use an integrated power function for signal linearization are reviewed as previously unavailable, new parameters for optimization.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Preparações Farmacêuticas/análise , Aerossóis/análise , Excipientes/química , Extratos Vegetais/química , Controle de Qualidade , Tecnologia Farmacêutica/métodos , Tecnologia Farmacêutica/normas , Temperatura
11.
AAPS PharmSciTech ; 21(3): 79, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974817

RESUMO

In order to investigate the correlation among energy input-related, drug-related, and stabilizer-related aspects for both top-down and bottom-up nanocrystal production, meloxicam nanosuspensions (NS) were produced by using three different methods (low-energy wet milling, high-pressure homogenization, and precipitation) and each method was optimized by using design of experiment (DoE). Box-Behnken design of 3 factors and 3 levels was applied for the optimization of each method. All the three models were found to be significant and the optimized process parameters were used for production of NS, respectively. Interestingly, by comparison of the top-down and bottom-up approaches, the influence of energy input (homogenization pressure or milling speed) from the instruments seemed not significant for top-down compared with bottom-up for this drug. Different mechanisms of homogenization (relatively high energy zone) and milling (relatively low energy zone) led to obtained various significant correlations for each method. Capsules containing nanocrystals were successfully produced by using a novel method applying NS (after wet bead milling and homogenization processes) as wetting agent for direct capsuling and showed superiority regarding as dissolution rate compared with the traditional two-step method (freeze-dried powder used for capsuling as the first step). Different NS preparation methodologies proved to have a direct influence on the following capsuling process and consequently, in the dissolution rate. This study also proved that residual DMSO in nanosuspension after precipitation process could affect the freeze-drying process, which might further alter the redispersion and influence the downstream processes.


Assuntos
Meloxicam/química , Tecnologia Farmacêutica/métodos , Cápsulas , Nanopartículas/química , Tamanho da Partícula , Solubilidade , Suspensões
12.
Eur J Pharm Biopharm ; 147: 102-110, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31899368

RESUMO

Electrospraying or electrohydrodynamic atomisation, i.e. the formation of tiny droplets from a jet of conductive liquid under the influence of an electric field, has been gaining in popularity as a particle engineering technique in recent years. In addition to general benefits for particle engineering, e.g. the ability to generate nanometre sized particles with a very narrow size distribution, electrospraying also possesses a number of characteristics, like its applicability at ambient conditions, which could make it especially interesting for formulating therapeutic proteins. However, as fully aqueous solutions of proteins tend to have relatively high electrical conductivities and surface tensions, obtaining a stable Taylor cone-jet mode for these solutions is inherently challenging. This is why in the majority of studies reporting the successful electrospraying of proteins, either emulsions, aqueous suspensions or a mixture of water and one or more organic solvents were used instead of fully aqueous solutions. Therefore, an ab initio electrospraying formulation development study was conducted, using only fully aqueous feed solutions containing protein stabilising excipients commonly used in spray- and freeze-drying of therapeutic proteins. The study included bovine serum albumin (BSA) as a model protein and consisted out of two parts: (1) a one parameter at a time screening study, designed to improve the understanding of how various formulation components influence relevant physicochemical properties and the electrospraying process and (2) two subsequent mixture design of experiments (DoE) studies, designed to aid in the statistical description and prediction of the influence of different protein-excipient combinations on the electrospraying process. Additionally, the influence of physicochemical properties relevant to the electrospraying process, i.e. the volumetric mass density, electrical conductivity, kinematic viscosity and surface tension, was assessed for all feed solutions included in the study.


Assuntos
Composição de Medicamentos/métodos , Excipientes/química , Soroalbumina Bovina/química , Tecnologia Farmacêutica/métodos , Estudos de Viabilidade , Liofilização , Hidrodinâmica , Tamanho da Partícula , Soroalbumina Bovina/administração & dosagem , Solventes/química , Tensão Superficial , Viscosidade , Água/química
13.
Pharm Biol ; 58(1): 131-137, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31967911

RESUMO

Context: Carbonized ginger, a type of charry herb, has been used as a hemostatic medicine since ancient times. However, there are some serious problems such as inhomogeneous heating and emitting smoke during processing with traditional stir-frying method.Objective: To investigate the feasibility to obtain carbonized ginger by stir-frying with sand instead of stir-frying method.Materials and methods: Dried-ginger (100 g) was processed by stir-frying for 30 min at 270 ± 10 °C, or by stir-frying with sand (1:10, w/w) for 8 min at 240 ± 5 °C. The HPLC fingerprint was established for two samples. The adsorption capacity and major components including tannins, gingerols, shogaols and gingerone were quantitated by UV and HPLC, respectively. The hemostatic effect by prothrombin time (PT) and activated partial thromboplastin time (APTT) was evaluated in vitro.Results: The similarity of the two samples for HPLC fingerprints was >0.93. The sand-fried samples showed significantly higher adsorption capacity compared with the stir-fried samples (4.915 vs. 4.593 mg/g; p < 0.05) and higher contents of major components (4.698 vs. 3.930 mg/g, 1.352 vs. 1.144 mg/g, 2.419 vs. 2.095 mg/g, 0.666 vs. 0.568 mg/g and 1.083 vs. 0.911 mg/g for tannins, gingerone, 6-shogaol, 8-shogaol and 10-shogaol, respectively; p < 0.05); while no significant differences were seen for 6-gingerol, 8-gingerol and 10-gingerol (p > 0.05). The PT and APTT values were similar between the stir-fried and sand-fried test groups and significantly lower compared to controls (p < 0.05).Conclusions: The carbonizing process by stir-frying with sand is superior to the stir-frying method for carbonized ginger.


Assuntos
Gengibre/química , Hemostáticos/farmacologia , Extratos Vegetais/farmacologia , Tecnologia Farmacêutica/métodos , Animais , Carbono/química , Cromatografia Líquida de Alta Pressão , Estudos de Viabilidade , Tempo de Tromboplastina Parcial , Extratos Vegetais/química , Tempo de Protrombina , Coelhos , Rizoma , Areia/química
14.
Biochim Biophys Acta Rev Cancer ; 1873(1): 188319, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678141

RESUMO

The treatment of cancer is still a major challenge. But tremendous progress in anticancer drug discovery and development has occurred in the last few decades. However, this progress has resulted in few effective oncology products due to challenges associated with anticancer drug delivery. Oral administration is the most preferred route for anticancer drug delivery, but the majority of anticancer drugs currently in product pipelines and the majority of those that have been commercially approved have inherently poor water solubility, and this cannot be mitigated without compromising their potency and stability. The poor water solubility of anticancer drugs, in conjunction with other factors, leads to suboptimal pharmacokinetic performance. Thus, these drugs have limited efficacy and safety when administered orally. The amorphous solid dispersion (ASD) is a promising formulation technology that primarily enhances the aqueous solubility of poorly water-soluble drugs. In this review, we discuss the challenges associated with the oral administration of anticancer drugs and the use of ASD technology in alleviating these challenges. We emphasize the ability of ASDs to improve not only the pharmacokinetics of poorly water-soluble anticancer drugs, but also their efficacy and safety. The goal of this paper is to rationalize the application of ASD technology in the formulation of anticancer drugs, thereby creating superior oncology products that lead to improved therapeutic outcomes.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Monitoramento de Medicamentos/métodos , Tecnologia Farmacêutica/métodos , Administração Oral , Antineoplásicos/química , Antineoplásicos/farmacocinética , Química Farmacêutica , Sistemas de Liberação de Medicamentos/tendências , Descoberta de Drogas/métodos , Descoberta de Drogas/tendências , Monitoramento de Medicamentos/tendências , Humanos , Solubilidade , Tecnologia Farmacêutica/tendências , Água/química
15.
Pharm Dev Technol ; 25(1): 20-27, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31017030

RESUMO

In pediatrics, it is crucial to ameliorate the unpleasant taste of oral pharmaceutical formulations in order to facilitate patient compliance. Scientists' attempt to develop modern products for children is included among the new trends in pharmaceutical technology. Designing the preparation procedures and selecting the age-appropriate dosage form should be based on a benefit-risk approach, taking into account safety, efficacy, ease of use and accessibility to the patient. Part of this process should examine the necessity for taste masking, considering organoleptic and physicochemical properties of the active pharmaceutical ingredient. This research describes the incorporation of metoclopramide hydrochloride in the form of a soft candy (jelly) containing pomegranate juice. The low cost excipients and the ease of preparation are such characteristics that qualify the proposed technique as one of the alternative methods for modern drug formulations. At the same time, metoclopramide is quantitatively determined by developing a reverse phase HPLC method. The method is accurate (%RSD = 2.63, %mean recovery = 100.75) and can be used for routine analysis. The stability of metoclopramide was satisfactory after 6 months of storage (recovery 103.43%). Dissolution of the drug exceeded 92%. The proposed formulation enclosing metoclopramide in a jelly is modern, palatable and can be administered to children.


Assuntos
Excipientes/química , Metoclopramida/química , Administração Oral , Doces , Química Farmacêutica/métodos , Alimentos , Humanos , Pediatria , Solubilidade , Paladar/efeitos dos fármacos , Tecnologia Farmacêutica/métodos
16.
J Pharm Biomed Anal ; 178: 112937, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31679845

RESUMO

Amorphous solid dispersions (ASDs) are single-phase amorphous systems, where drug molecules are molecularly dispersed (dissolved) in a polymer matrix. The molecular dispersion of the drug molecules is responsible for their improved dissolution properties. Unambiguously establishing the phase behavior of the ASDs is of utmost importance. In this paper, we focused on the complementary nature of (modulated) differential scanning calorimetry ((m)DSC) and X-ray powder diffraction (XRPD) to elucidate the phase behavior of ASDs as demonstrated by a critical discussion of practical real-life examples observed in our research group. The ASDs were manufactured by either applying a solvent-based technique (spray drying), a heat-based technique (hot melt extrusion) or mechanochemical activation (cryo-milling). The encountered limiting factors of XRPD were the lack of sensitivity for small traces of crystallinity, the impossibility to differentiate between distinct amorphous phases and its impossibility to detect nanocrystals in a polymer matrix. In addition, the limiting factors of (m)DSC were defined as the well-described heat-induced sample alteration upon heating, the interfering of residual solvent evaporation with other thermal events and the coinciding of enthalpy recovery with melting events. In all of these cases, the application of a single analytical technique would have led to erroneous conclusions, whilst the combination of (m)DSC and XRPD elucidated the true phases of the ASD.


Assuntos
Polímeros/química , Pós/química , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Cristalização/métodos , Temperatura Alta , Nanopartículas/química , Sensibilidade e Especificidade , Solubilidade/efeitos dos fármacos , Solventes/química , Tecnologia Farmacêutica/métodos , Difração de Raios X/métodos
17.
Curr Pharm Biotechnol ; 21(5): 364-373, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31845630

RESUMO

BACKGROUND: Bacteriophages are viruses, which are obligate parasites of specific bacteria for the completion of their lifecycle. Bacteriophages could be the possible alternative to antibioticresistant bacterial diseases. With this objective, extensive research in different fields is published which are discussed in this article. METHODS: After a review of bacteriophage therapy, bacteriophages were found to be effective against the multidrug-resistant bacteria individually or synergistically with antibiotics. They were found to be more effective, even better than the bacteria in the development of a vaccine. RESULTS: Apart from the bacteriophages, their cell contents like Lysin enzymes were found equally very much effective. Only the major challenge faced in phage therapy was the identification and characterization of bacteria-specific phages due to the wide genetic diversity of bacterial populations. Similarly, the threshold level of bacteriophages to act effectively was altered by ultraviolet radiation and heat exposure. CONCLUSION: Thus, bacteriophage therapy offers promising alternatives in the treatment of antibioticresistant bacteria in different fields. However, their effectiveness is determined by a triad of bacteriophages (type & quantity), host (bacteria) and environmental factors.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Bacteriófagos/crescimento & desenvolvimento , Farmacorresistência Bacteriana Múltipla , Terapia por Fagos/métodos , Terapia por Fagos/tendências , Tecnologia Farmacêutica/métodos , Animais , Bacteriófagos/efeitos da radiação , Ensaios Clínicos como Assunto , Temperatura Alta , Humanos , Raios Ultravioleta
18.
Drug Deliv ; 27(1): 54-65, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31858849

RESUMO

Didymin is a dietary flavonoid that first found in citrus fruits, and possesses antioxidant properties. Our preliminary experiments first discovered that didymin was able to sensitize the resistant cancer cells against chemotherapeutics and combat multidrug resistance. However, its poor aqueous solubility and resultant low bioavailability limit its potentials as an adjuvant phytochemical drug for chemotherapy. Thus, this study prepared the inclusion complex of didymin with ß-cyclodextrin and 2-hydroxypropyl-ß-cyclodextrin to improve its bioavailability and then evaluate their chemosensitization effects. The didymin inclusion complexes formulation was prepared and their host-guest structure was characterized by FT-IR, PXRD, DSC, and SEM techniques. In vitro/in vivo results demonstrated that didymin inclusion complex enhanced its water solubility and orally bioavailability. Furthermore, didymin inclusion complex exerted considerable chemosensitivity potency, and improve the anti-tumor effects of chemotherapeutics in vivo. Therefore, didymin inclusion complex could provide a safe, effective, economical, and adjuvant drug for future treatment of chemoresistant cancers.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Flavonoides/administração & dosagem , Flavonoides/farmacologia , Glicosídeos/administração & dosagem , Glicosídeos/farmacologia , Tecnologia Farmacêutica/métodos , beta-Ciclodextrinas/química , Animais , Varredura Diferencial de Calorimetria , Flavonoides/farmacocinética , Glicosídeos/farmacocinética , Células Endoteliais da Veia Umbilical Humana , Humanos , Células MCF-7 , Masculino , Células PC12 , Ratos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
19.
Drug Deliv ; 27(1): 110-127, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31885288

RESUMO

Amorphous solid dispersions (ASDs) can increase the oral bioavailability of poorly soluble drugs. However, their use in drug development is comparably rare due to a lack of basic understanding of mechanisms governing drug liberation and absorption in vivo. Furthermore, the lack of a unified nomenclature hampers the interpretation and classification of research data. In this review, we therefore summarize and conceptualize mechanisms covering the dissolution of ASDs, formation of supersaturated ASD solutions, factors responsible for solution stabilization, drug uptake from ASD solutions, and drug distribution within these complex systems as well as effects of excipients. Furthermore, we discuss the importance of these findings on the development of ASDs. This improved overall understanding of these mechanisms will facilitate a rational ASD formulation development and will serve as a basis for further mechanistic research on drug delivery by ASDs.


Assuntos
Excipientes/química , Farmacocinética , Tecnologia Farmacêutica/métodos , Disponibilidade Biológica , Cristalização , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Solubilidade , Tensoativos/química
20.
Eur J Pharm Sci ; 141: 105089, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626967

RESUMO

The goals of this work were to evaluate if high-speed electrospinning can be used as a gentle and continuous drying technology to produce protein-containing cyclodextrin-based fibers from an aqueous solution and to convert the produced protein-cyclodextrin fibers into a directly compressible powder. A 400 mL/h feeding rate was used during the electrospinning experiments, corresponding to a ~270 g/h production rate of the dried material. The produced fibers were collected in a cyclone. The fibers were found grindable without secondary drying, and the ground powder was mixed with tableting excipients and was successfully tableted by direct compression. The model protein-type drug (ß-galactosidase) remained stable during each of the processing steps (electrospinning, grinding, tableting) and after 6 months of storage at room temperature in the tablets. The obtained results demonstrate that high speed electrospinning can be a gentle alternative to traditional drying methods used for protein-type drugs, and that tablet formulation is achievable from the electrospun material prepared this way.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Tecnologia Farmacêutica/métodos , beta-Galactosidase/química , Dessecação , Estabilidade Enzimática , Pós , Comprimidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA