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1.
Nat Commun ; 11(1): 4450, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895379

RESUMO

Hollow multishelled structures (HoMSs), with relatively isolated cavities and hierarchal pores in the shells, are structurally similar to cells. Functionally inspired by the different transmission forms in living cells, we studied the mass transport process in HoMSs in detail. In the present work, after introducing the antibacterial agent methylisothiazolinone (MIT) as model molecules into HoMSs, we discover three sequential release stages, i.e., burst release, sustained release and stimulus-responsive release, in one system. The triple-shelled structure can provide a long sterility period in a bacteria-rich environment that is nearly 8 times longer than that of the pure antimicrobial agent under the same conditions. More importantly, the HoMS system provides a smart responsive release mechanism that can be triggered by environmental changes. All these advantages could be attributed to chemical diffusion- and physical barrier-driven temporally-spatially ordered drug release, providing a route for the design of intelligent nanomaterials.


Assuntos
Antibacterianos/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Portadores de Fármacos/química , Nanoestruturas/química , Antibacterianos/farmacocinética , Preparações de Ação Retardada/farmacocinética , Difusão , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microesferas , Tiazóis/administração & dosagem , Tiazóis/farmacocinética
2.
Int J Nanomedicine ; 15: 5389-5403, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801695

RESUMO

Hypothesis: Developing oral formulations to enable effective release of poorly water-soluble drugs like progesterone is a major challenge in pharmaceutics. Coaxial electrospray can generate drug-loaded nanoparticles of strategic compositions and configurations to enhance physiological dissolution and bioavailability of poorly water-soluble drug progesterone. Experiments: Six formulations comprising nanoparticles encapsulating progesterone in different poly(lactide-co-glycolide) (PLGA) matrix configurations and compositions were fabricated and characterized in terms of morphology, molecular crystallinity, drug encapsulation efficiency and release behavior. Findings: A protocol of fabrication conditions to achieve 100% drug encapsulation efficiency in nanoparticles was developed. Scanning electron microscopy shows smooth and spherical morphology of 472.1±54.8 to 588.0±92.1 nm in diameter. Multiphoton Airyscan super-resolution confocal microscopy revealed core-shell nanoparticle configuration. Fourier transform infrared spectroscopy confirmed presence of PLGA and progesterone in all formulations. Diffractometry indicated amorphous state of the encapsulated drug. UV-vis spectroscopy showed drug release increased with hydrophilic copolymer glycolide ratio while core-shell formulations with progesterone co-dissolved in PLGA core exhibited enhanced release over five hours at 79.9±1.4% and 70.7±3.5% for LA:GA 50:50 and 75:25 in comparison with pure progesterone without polymer matrix in the core at 67.0±1.7% and 57.5±2.8%, respectively. Computational modeling showed good agreement with the experimental drug release behavior in vitro.


Assuntos
Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Progesterona/administração & dosagem , Progesterona/farmacocinética , Disponibilidade Biológica , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Microscopia Eletrônica de Varredura , Nanopartículas/administração & dosagem , Tamanho da Partícula , Solubilidade , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Água/química , Difração de Raios X
3.
AAPS PharmSciTech ; 21(5): 181, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32607628

RESUMO

Cocrystals have gained a lot of consideration regarding its superior role in enhancement of solubility and dissolution of the included API. Cocrystals could be converted to coamorphous systems via different techniques like milling and quench cooling; however, the use of spray-drying technique has not been investigated before. So, the aim of this study was to explore the effect of spray drying on the amorphization of indomethacin/nicotinamide, INDNIC, as model cocrystals. Spray-drying operating parameters were optimized using the Taguchi design of experiment for maximum powder yield and low moisture content. The obtained INDNIC spray-dried cocrystals were characterized for their degree of crystallinity, morphology, moisture content, and dissolution performance. In addition, stability study was performed at different temperature and humidity conditions. Experimental design results delineate that spray-drying inlet temperature and cocrystal concentrations as the most influential factors for maximum powder yield and low moisture content. Powder X-ray diffraction and differential scanning calorimetry studies revealed the conversion of INDNIC cocrystals to a partial coamorphous or coamorphous structure without dissociation of INDNIC molecular structure. INDNIC coamorphous powders showed a significantly higher release of IND compared with cocrystals and remain physically stable for 2 months when stored in the refrigerator.


Assuntos
Dessecação/métodos , Estabilidade de Medicamentos , Indometacina/química , Niacinamida/química , Varredura Diferencial de Calorimetria , Composição de Medicamentos/métodos , Estrutura Molecular , Pós/química , Solubilidade , Difração de Raios X
4.
J Mycol Med ; 30(3): 101003, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32586733

RESUMO

OBJECTIVE: In order to improve the effect of ketoconazole, poly-lactic acid (PLA) nanoparticles containing ketoconazole were prepared, characterized and tested against dermatophytes and Candida spp planktonic and biofilm cells. METHODS: The ketoconazole-PLA nanoparticles obtained by nanoprecipitation were characterized using dynamic light scattering, scanning electron microscopy, transmission electron microscopy, and differential scanning calorimetry. In addition, quantification of encapsulated ketoconazole and the in vitro release profile were determined. Antifungal susceptibility tests against dermatophytes Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum and yeasts Candida albicans, C. dubliniensis, C. krusei, C. parapsilosis, and C. tropicalis were performed. RESULTS: Spherical nanoparticles, with a mean diameter of 188.5nm and an encapsulation efficiency of 45% ketoconazole, were obtained. The nanoparticles containing ketoconazole had superior antifungal activity against all tested fungi strains than free ketoconazole. Inhibition of yeast biofilm formation was also achieved. CONCLUSION: Ketoconazole-PLA nanoparticles resulted in better antifungal activity of ketoconazole nanoparticles than free drug against dermatophytes and Candida species, indicating a promising tool for the development of therapeutic strategies.


Assuntos
Antifúngicos/administração & dosagem , Arthrodermataceae/efeitos dos fármacos , Candida/efeitos dos fármacos , Portadores de Fármacos , Cetoconazol/administração & dosagem , Nanopartículas/química , Poliésteres/química , Antifúngicos/farmacocinética , Arthrodermataceae/fisiologia , Biofilmes/efeitos dos fármacos , Candida/fisiologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Cetoconazol/farmacocinética , Teste de Materiais , Testes de Sensibilidade Microbiana , Resultado do Tratamento
5.
Int J Mol Med ; 46(1): 3-16, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32377694

RESUMO

In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS­COV­2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID­19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais , Infecções por Coronavirus/classificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Composição de Medicamentos/métodos , Composição de Medicamentos/normas , Composição de Medicamentos/tendências , Desenvolvimento de Medicamentos/métodos , Desenvolvimento de Medicamentos/normas , Desenvolvimento de Medicamentos/tendências , Humanos , Segurança do Paciente , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Resultado do Tratamento , Vacinação/efeitos adversos , Potência de Vacina , Vacinas Virais/classificação , Vacinas Virais/normas , Vacinas Virais/provisão & distribução , Vacinas Virais/uso terapêutico
7.
AAPS PharmSciTech ; 21(5): 154, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32449146

RESUMO

Moving from batch to continuous manufacturing (CM) requires implementation of process analytical technology (PAT), as it is crucial to monitor and control these processes. CM of semi-solids has been demonstrated but implementation of a broader range of PAT tools with in- or on-line process interfacing at the end of the CM line has not been demonstrated. The goal of this work was to continuously manufacture creams and to investigate whether in- and on-line measurement of viscosity, changes in the concentration of active pharmaceutical ingredient (API), and pH could be used to support optimization of a model cream product. Additionally, the torque of the mixers was assessed for determination of the physical properties of the cream. Two Raman probes with different probe optics were compared for characterization of the API concentration. The API concentration, amount of neutralizer, and mixing speed of the CM line were systematically varied. Both the PhAT probe with a larger sampling volume and immersion Raman probe with a smaller sampling volume could detect the step changes in the API concentration. The torque from the mixer was compared with the viscosity measurements, but the torque signal could not be correlated with the viscosity due to the dynamic nature of the polymer conformation and the time-dependency of this property. Adjustment of pH of the cream could be monitored with the current installation. The investigated PAT tools could be implemented into a continuous line and, further, be used to support the optimization of a model cream composition and related process parameters.


Assuntos
Composição de Medicamentos/métodos , Emulsões , Polímeros , Indústria Farmacêutica , Excipientes , Concentração de Íons de Hidrogênio , Pomadas , Análise Espectral Raman , Torque , Viscosidade
8.
AAPS PharmSciTech ; 21(4): 133, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415395

RESUMO

Phage therapy has gained prominence due to the increasing pathogenicity of "super bugs" and the rise of their multidrug resistance to conventional antibiotics. Dry state formulation of therapeutic phage is attractive to improve their "druggability" by increasing their shelf life, improving their ease of handling, and ultimately retaining their long-term potency. The use and selection of excipients are critical to stabilize phage in solid formulations and protect their viability from stresses encountered during the solidification process and long-term storage prior to use. Here, this review focuses on the current classes of excipients used to manufacture dry state phage formulations and their ability to stabilize and protect phage throughout the process, as discussed in the literature. We provide perspective of outstanding challenges involved in the formulation of dry state phage. We suggest strategies to improve excipient identification and selection, optimize the potential excipient combinations to improve phage viability during formulation, and evaluate new methodologies that can provide greater insight into phage-excipient interactions to improve design criteria to improve formulation of dry state phage therapeutics. Addressing these challenges opens up new opportunities to re-design and re-imagine phage formulations for improved efficacy as a pharmaceutical product.


Assuntos
Bacteriófagos/química , Produtos Biológicos/química , Composição de Medicamentos/métodos , Excipientes/química , Animais , Produtos Biológicos/administração & dosagem , Estabilidade de Medicamentos , Excipientes/administração & dosagem , Humanos
9.
Int J Pharm Compd ; 24(3): 206-212, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401740

RESUMO

Viscosity plays many roles in pharmaceutical dosage forms, especially solutions, suspensions, emulsions and gels. It is important in increasing both physical and chemical stability as well as enhancing patient compliance by making drug products easier to handle and administer. There are numerous different viscosity-enhancing agents that can be used and tailored to specific needs based upon their solubility, pH range of effectiveness, concentration required, esthetics, and other factors. Preparation and proper incorporation into dosage forms is important to obtain the desired characteristics of the finished drug product as well as assuring microbial stability. Appropriate viscosity- increasing additives can aid in ensuring patient compliance with the compounded medication.


Assuntos
Emulsões/química , Excipientes , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Humanos , Solubilidade , Viscosidade
10.
Int J Pharm Compd ; 24(3): 200-205, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401739

RESUMO

Drug stability can be affected by light, moisture, oxygen, temperature, and other factors. About 25% of drugs on the market today have some requirement for light-resistant packaging. The rate of drug degradation varies from rapid to slow among different categories and examples of drugs. When compounding very light-sensitive drugs, environmental controls should be implemented and exposure to any light may need to be minimized. Packaging of the final compounded product is critical as well as light protection during storage, distribution, and when held at the patient's home for administration. Pharmacists have access to different sources of information that provide information on which drugs need protection from light.


Assuntos
Embalagem de Medicamentos/métodos , Preparações Farmacêuticas , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Humanos , Preparações Farmacêuticas/química , Farmacêuticos
11.
Int J Pharm Compd ; 24(3): 215-220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401741

RESUMO

Intravenous admixture compounding requires knowledge of stability, compatibility, and incompatibility issues related to the complete composition and formulation. In evaluating an intravenous admixture, one is not just concerned with the active ingredients but also with all the excipients. Both active pharmaceutical ingredients and excipients used in the formulations of commercially available products may vary among manufacturers and can influence drug compatibility and stability. Clinical pharmaceutics includes the study and application of pharmaceutics to clinical compounding situations to aid in the evaluation of each intravenous admixture. A critical aspect of successful intravenous admixture preparation is the prevention or minimization of particulate matter in the finished product. This article discusses the source, method of prevention, and detection of particulates in intravenous admixtures.


Assuntos
Administração Intravenosa , Excipientes , Composição de Medicamentos/métodos , Estabilidade de Medicamentos
12.
AAPS PharmSciTech ; 21(5): 136, 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32419122

RESUMO

The paclitaxel protein-bound particles for injectable suspension (marketed under the brand name Abraxane®) contains nanosized complexes of paclitaxel and albumin. The molecular interaction between paclitaxel and albumin within the higher-order nanostructure is analytically challenging to assess, as is any correlation of differences to differences in therapeutic effect. However, because the higher-order nanostructures may affect the paclitaxel release, a suitable in vitro assay to detect potential differences in paclitaxel release between comparator lots and products is desirable. Herein, solution NMR spectroscopy with a T2-filtering technique was developed to detect paclitaxel signal while suppressing albumin signals to follow the released paclitaxel in the NMR tube upon dilution. The non-invasive nature of NMR allows for precise measurement of a full range of dilution-induced drug release percentage from 14 to 92% without any sample extraction. The critical concentration of the drug product (DP) at 50% of release was 0.63 ± 0.04 mg/mL in PBS buffer. In addition, 2D diffusion ordered NMR spectroscopy (DOSY) results revealed that the released paclitaxel experiencing slightly slowed diffusion rates than free paclitaxel, which was attributed to paclitaxel in equilibrium with albumin-bound states. Collectively, the dilution-based NMR method offered an analytical approach to investigate physicochemical attributes of complex injectable products with minimal needed sample preparation and perturbation to nanoparticle formulation.


Assuntos
Albuminas/química , Composição de Medicamentos/métodos , Espectroscopia de Ressonância Magnética/métodos , Nanopartículas/química , Paclitaxel/administração & dosagem , Difusão , Paclitaxel/química , Tamanho da Partícula , Padrões de Referência , Solubilidade , Suspensões
13.
Pharm Res ; 37(6): 91, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385723

RESUMO

PURPOSE: Bevacizumab (BCZ) is a recombinant monoclonal antibody that inhibits the biological activity of the vascular endothelial growth factor, which has an important role in angiogenesis for tumoral growth and progression. In this way, our objective was to develop chitosan-coated lipid-core nanocapsules functionalized with BCZ by an organometallic complex using gold-III. METHODS: The formulation was produced and characterized in relation to physicochemical characteristics. Furthermore, the antitumoral and antiangiogenic activities were evaluated against C6 glioma cell line and chicken embryo chorioallantoic membrane (CAM), respectively. RESULTS: Final formulation showed nanometric size, narrow polydispersity, positive zeta potential and gold clusters size lower than 2 nm. BCZ in aqueous solution (0.01-0.10 µmol L-1) did not show cytotoxic activity in vitro against C6 glioma cell line; although, MLNC-Au-BCZ showed cytotoxicity with a median inhibition concentration of 30 nmol L-1 of BCZ. Moreover, MLNC-Au-BCZ demonstrated cellular internalization dependent on incubation time and BCZ concentration. BCZ solution did not induce significant apoptosis as compared to MLNC-Au-BCZ within 24 h of treatment. CAM assay evidenced potent antiangiogenic activity for MLNC-Au-BCZ, representing a decrease of 5.6 times in BCZ dose comparing to BCZ solution. CONCLUSION: MLNC-Au-BCZ is a promising product for the treatment of solid tumors.


Assuntos
Inibidores da Angiogênese/química , Bevacizumab/química , Quitosana/química , Glioma/tratamento farmacológico , Ouro/química , Lipídeos/química , Nanocápsulas/química , Inibidores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Bevacizumab/metabolismo , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Composição de Medicamentos/métodos , Hexoses/química , Humanos , Lectinas de Plantas/química , Polissorbatos/química , Proteínas de Soja/química , Propriedades de Superfície , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Pharm Res ; 37(6): 92, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32394200

RESUMO

PURPOSE: The aim of the study was to evaluate organogel nanoparticles as a lipophilic vehicle to increase the oral bioavailability of poorly soluble compounds. Efavirenz (EFV), a Biopharmaceutical Classification System (BCS) Class II, was used as drug model. METHODS: Organogel nanoparticles loaded with EFV were formulated with sunflower oil, 12-hydroxystearic acid (HSA) and polyvinyl alcohol (PVA). Various parameters have been investigated in the current study such as (i) the release profile of organogel assessed by USP 4 cell flow dialysis, (ii) the impact of organogel on intestinal absorption, using Caco-2 cells as in vitro model and jejunum segments as ex vivo assay and (iii) the bioavailability of organogel following oral pharmacokinetic study. RESULTS: 250-300 nm spherical particles with a final concentration of 4.75 mg/mL drug loading were obtained, corresponding to a thousand fold increase in EFV solubility, combined to a very high encapsulation efficiency (>99.8%). Due to rapid diffusion, drug was immediately released from the nanoparticles. The biopharmaceutical evaluation on ex vivo jejunum segments demonstrated an increased absorption of EFV from organogel nanoparticles compare to a native EFV suspension. In vitro assays combining Caco-2 cell cultures with TEM and confocal microscopy demonstrated passive diffusion, while paracellular integrity and endocytosis activity remain expelled. Oral pharmacokinetics of EFV organogel nanoparticles improve oral bioavailability (Fr: 249%) and quick absorption compared to EFV suspension. CONCLUSION: Organogel nanoparticles increase the bioavailability of BCS Class II drugs. The main phenomena is simply oil transfer from the gelled particles through the cell membrane.


Assuntos
Benzoxazinas/química , Portadores de Fármacos/química , Géis/química , Nanocápsulas/química , Álcool de Polivinil/química , Ácidos Esteáricos/química , Óleo de Girassol/química , Animais , Benzoxazinas/administração & dosagem , Benzoxazinas/farmacocinética , Disponibilidade Biológica , Células CACO-2 , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Difusão , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Excipientes/química , Humanos , Absorção Intestinal , Masculino , Solubilidade , Suspensões/química , Distribuição Tecidual
15.
Pharm Res ; 37(6): 99, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32435855

RESUMO

PURPOSE: To evaluate the performance of artificial membranes in in vitro lipolysis-permeation assays useful for absorption studies of drugs loaded in lipid-based formulations (LBFs). METHODS: Polycarbonate as well as PVDF filters were treated with hexadecane, or lecithin in n-dodecane solution (LiDo) to form artificial membranes. They were thereafter used as absorption membranes separating two compartments mimicking the luminal and serosal side of the intestine in vitro. Membranes were subjected to dispersions of an LBF that had been digested by porcine pancreatin and spiked with the membrane integrity marker Lucifer Yellow (LY). Three fenofibrate-loaded LBFs were used to explore the in vivo relevance of the assay. RESULTS: Of the explored artificial membranes, only LiDo applied to PVDF was compatible with lipolysis by porcine pancreatin. Formulation ranking based on mass transfer in the LiDo model exposed was the same as drug release in single-compartment lipolysis. Ranking based on observed apparent permeability coefficients of fenofibrate with different LBFs were the same as those obtained in a cell-based model. CONCLUSIONS: The LiDo membrane was able to withstand lipolysis for a sufficient assay period. However, the assay with porcine pancreatin as digestive agent did not predict the in vivo ranking of the assayed formulations better than existing methods. Comparison with a Caco-2 based assay method nonetheless indicates that the in vitro in vivo relationship of this cell-free model could be improved with alternative digestive agents.


Assuntos
Portadores de Fármacos/química , Fenofibrato/química , Lipídeos/química , Lipólise , Membranas Artificiais , Administração Oral , Adsorção , Alcanos/química , Animais , Bioensaio/métodos , Células CACO-2 , Digestão , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Excipientes/química , Fenofibrato/administração & dosagem , Humanos , Lecitinas/química , Modelos Biológicos , Pancreatina/metabolismo , Permeabilidade , Solubilidade , Suínos
16.
Pharm Res ; 37(6): 100, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32436083

RESUMO

PURPOSE: We investigated the potential correlations between skin barrier integrity and hydrophilic drugs distribution in skin in the presence of different types of penetration enhancers (PEs) and their combinations. METHODS: We measured skin conductivity to evaluate skin barrier integrity before and after the topical application of different chemical PEs, physical PE, peptide PE and their combinations in vitro. We also investigated their effect on the skin distribution profiles of two hydrophilic model drugs, Fluorescein sodium (376 Da) and Fluorescein isothiocyanate-dextrans 10 (10 KDa). RESULTS: The physical PE significantly increased the skin conductivity compared to all other PEs, while the peptide PE had no effect on it. The drug deposition in different skin layers was not only dependent on PE applied but also its own molecular weight. We further found two excellent correlations: one (R2 = 0.9388) between skin barrier integrity and total skin absorption of FNa and another one(R2 = 0.9212) between skin barrier integrity and the deposition of FNa in dermis and receptor in presence of chemical or physical PEs and their combinations. CONCLUSIONS: The total skin absorption or the deposition in dermis and receptor of small hydrophilic drug in the presence of chemical and physical PEs and their combinations show a good correlation with skin barrier integrity. However, such correlations hold true neither for large hydrophilic drug nor for peptide PE. All good relationships found in this work will allow screening suitable PEs or combinations by measuring the skin conductivity induced by corresponding PEs. Graphical Abstract The total skin absorption of small hydrophilic drug shows a good correlation with skin barrier integrity in the presence of chemical and physical penetration enhancers and their combinations. However, such a correlation hold true neither for large hydrophilic drug nor for peptide penetration enhancer.


Assuntos
Melhoramento Biomédico/métodos , Portadores de Fármacos/química , Peptídeos/química , Preparações Farmacêuticas/química , Absorção Cutânea/efeitos dos fármacos , Pele/metabolismo , Administração Cutânea , Animais , Dextranos/administração & dosagem , Dextranos/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Excipientes/química , Fluoresceína/administração & dosagem , Fluoresceína/química , Fluoresceína-5-Isotiocianato/administração & dosagem , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/química , Cobaias , Humanos , Interações Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Conformação Molecular , Estrutura Molecular , Peso Molecular , Permeabilidade , Preparações Farmacêuticas/administração & dosagem , Solubilidade , Relação Estrutura-Atividade , Distribuição Tecidual
17.
Artigo em Inglês | MEDLINE | ID: mdl-32330807

RESUMO

Honey-processed Astragalus is a dosage form of radix Astragali processed with honey, which is deemed to contain better qi-tonifying effects in traditional Chinese medicine theroy. Our previous study has demonstrated that honey-processed Astragalus exhibited a better effect on reinforcing qi (vital energy) and immune improvement toward spleen qi deficiency compared with radix Astragali. However, the detailed mechanisms related to qi-tonifying effects of honey-processed Astragalus is still unclear. In this study, we evaluated the qi-tonifying effects of honey-processed Astragalus on spleen qi deficiency rats and predicted the mechanisms by aggregating metabonomics, lipidomics and network pharmacology. The results revealed that body weights, symptom scores, the levels of red blood cell, white blood cell, lymphocyte, spleen and thymus indexes, and three cytokines (TNF-α, IL-6, IFN-γ) in honey-processed Astragalus treated rats were improved in comparison with spleen qi deficiency rats. In parallel, based on the 26 biomarkers screened in metabonomics and lipidomics, we inferred that glycerophospholipid metabolism significantly regulated in pathway analysis was connected with qi-tonifying effects. Moreover, the network pharmacology analysis concluded that the compounds targets of honey-processed Astragalus CDK2, NOS3, MAPK14, PTGS1 and PTGS2 interacted with markers targets PLA2G(s) family and LYPLA1 could be responsible for regulation of glycerophospholipid metabolism to develop qi-tonifying effects. What's more, the above processes were possibly through VEGF signaling and MAPK signaling pathways.


Assuntos
Astrágalo (Planta)/química , Citocinas/sangue , Medicamentos de Ervas Chinesas/farmacologia , Espectrometria de Massas em Tandem/métodos , Animais , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Citocinas/metabolismo , Composição de Medicamentos/métodos , Eritrócitos/efeitos dos fármacos , Feminino , Mel , Humanos , Leucócitos/efeitos dos fármacos , Lipidômica , Linfócitos/efeitos dos fármacos , Qi , Ratos , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos
18.
Int J Pharm Compd ; 24(2): 121-126, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32196475

RESUMO

The study of intravenous admixture compatibility is an excellent application of "clinical pharmaceutics." Clinical pharmaceutics involves the study and application of pharmaceutics and pharmaceutic (physical pharmacy/ chemistry) principles to clinical compounding situations to aid in the evaluation of each intravenous admixture. This series includes compatibility and stability considerations in intravenous admixture compounding. Part 2 of this series of articles discussed many factors that should be considered that may give rise to compatibility concerns, as well as drug sorption issues. In this issue (Part 3), there is a discussion on the methods and techniques that can be used to decrease the occurrence and incidence of incompatibilities, along with some alternate techniques to consider when some approaches do not seem feasible.


Assuntos
Composição de Medicamentos/métodos , Farmácia , Administração Intravenosa , Biofarmácia , Incompatibilidade de Medicamentos
19.
Int J Pharm Compd ; 24(2): 140-147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32196476

RESUMO

In New Zealand, there are no liquid formulations of omeprazole commercially available, therefore suspensions must be extemporaneously compounded from solid dosage forms for patients with swallowing difficulties. The funding for solid dosage forms of omeprazole changes frequently, often every one to two years, without consideration of the impact this may have when extemporaneously compounded liquid dosage forms are required. This study examined suspensions compounded from various solid dosage forms of omeprazole with the purpose of identifying suitable quality formulations and evaluating their chemical and physical stability. Six different solid dosage forms of omeprazole that are available in New Zealand, including capsules, tablets, and powder, were used to prepare 2-mg/mL suspensions in 8.4% w/v sodium bicarbonate solution. The suspensions were then assessed visually for quality and by quantifying sedimentation rate over 120 minutes. Two products, stored in amber bottles at either 4°C or 25°C, demonstrated acceptable quality over a 30-day period whilst monitoring physical and chemical stability on day 0, 7, 14, 20, and 30. Four of the formulated suspensions were deemed to be of poor quality due to either a lack of uniformity or rapid sedimentation, attributes that could lead to inaccurate dosing. Acceptable quality suspensions were prepared from Losec and Dr. Reddy's brands of omeprazole 20-mg capsules. For both brands, a change in color was observed after 20 days and 7 days when stored at 4°C and 25°C, respectively. Chemical stability was determined using a stability-indicating high-performance liquid chromatographic method, with >90% of the active remaining for 30 days when kept at 4°C, and 20 days when stored at 25°C. Not all brands are suitable for extemporaneously compounding omeprazole suspensions. Losec and Dr. Reddy's brands of capsules were suitable to prepare quality omeprazole suspensions. Omeprazole suspensions compounded from these products are stable for 20 days if stored at 4°C and protected from light.


Assuntos
Omeprazol , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Humanos , Omeprazol/química , Suspensões , Comprimidos
20.
Int J Pharm Compd ; 24(2): 148-155, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32196477

RESUMO

Orodispersible tablets disintegrate rapidly (within 3 minutes) in the oral cavity and release the medicament before swallowing. The mode of disintegrant addition might affect the properties of orodispersible tablets. The objective of this study was to formulate and evaluate orodispersible tablets by studying different modes of disintegration addition with varying concentrations of disintegrants. The wet granulation method was used to produce the orodispersible tablets. Two methods of disintegration addition were compared (i.e., intragranular, extragranular). Three disintegrants (i.e., cornstarch, sodium starch glycolate, crospovidone) were used at three levels (5%, 10%, and 15%) in the study. The formulations were tested for the powder flowability (angle of repose) and characterized physically (hardness, weight, thickness, friability, disintegration time). The mangosteen pericarp extract was used as a model active pharmaceutical ingredient to be incorporated into the optimum formulation. It was observed that the extragranular method produced granules with better flowability compared to that of the intragranular method. Crospovidone was found as the most efficient disintegrant among the three. The optimum formulation selected was one with the highest concentration of crospovidone (15%), which showed the fastest disintegration time. The mode of disintegrant addition into the orodispersible tablets formulation was found to show a marked difference in the disintegration, as well as other physical characteristics of the orodispersible tablets where the extragranular mode of addition showed better property, which caused the orodispersible tablets to disintegrate the fastest.


Assuntos
Composição de Medicamentos/métodos , Excipientes , Comprimidos/química , Administração Oral , Química Farmacêutica/métodos , Excipientes/química , Dureza , Pós , Solubilidade
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