Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
AAPS PharmSciTech ; 24(2): 67, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36788171

RESUMO

It is well-known that plenty of active pharmaceutical ingredients (API) inherently possess an unpleasant taste, which influences the acceptance of patients, especially children. Therefore, manufacturing taste-masked dosage forms has attracted a lot of attention. This review describes in detail the taste-masking technologies based on the difference in the taste transmission mechanism which is currently available. In particular, the review highlights the application of various methods, with a special focus on how to screen the appropriate masking technology according to the properties of API. Subsequently, we overviewed how to assess taste-masking efficacy, guiding researchers to rationally design taste-masking formulations.


Assuntos
Paladar , Tecnologia Farmacêutica , Criança , Humanos , Administração Oral , Composição de Medicamentos/métodos , Tecnologia Farmacêutica/métodos , Tecnologia
2.
J Mater Chem B ; 11(4): 865-878, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36594907

RESUMO

Drug resistance caused by facultative intracellular bacteria such as Salmonella typhimurium (S. typhimurium) is still a tough challenge. Bacteria phagocytosed by macrophages have evolved a variety of mechanisms to defend against host attack, and the poor entry of antibiotics into infected macrophages is conducive to the survival of intracellular bacteria. In this report, we prepared a quasi-opsonized chloramphenicol (Chl)-loaded micellar system (B-mLBP-M/Chl) assembled by a bacterial lipase-sensitive polymer with a conjugate of lipopolysaccharide-binding protein (LBP) analog and biotin (B) as a ligand, which could eliminate drug-resistant S. typhimurium with quasi-opsonization via 3 steps: (i) target and release antibiotics on bacteria lipase, (ii) opsonize S. typhimurium to be digested by the macrophage, and (iii) activate the macrophage for fighting. The B-mLBP-M/Chl could target bacterial LPS through mLBP by simulating the N-terminal sequence of native LBP, exhibiting a high ability to target the localized infection site in mice. It could also activate the phagocytosis of macrophages via coupled biotin, cooperating with antibiotics and effectively improving the survival of mice with little pathological damage to tissues. Moreover, compared with native opsonin, B-mLBP does not cause an excessive inflammatory response and could recover homeostasis after exerting the quasi-opsonization by regulating the levels of pro-inflammatory cytokines and anti-inflammatory cytokines. With a universal target site for Gram-negative bacteria and macrophage activation, this B-mLBP-M/Chl could be applied to other bacterial infections in the future. In particular, this analog may also serve as a useful template to design safe artificial opsonin, which could be a ligand for drug delivery systems or prodrugs.


Assuntos
Infecções Bacterianas , Proteínas Opsonizantes , Animais , Camundongos , Proteínas Opsonizantes/farmacologia , Micelas , Biotina/farmacologia , Ligantes , Macrófagos , Citocinas , Antibacterianos/farmacologia
3.
Drug Deliv Transl Res ; 12(6): 1376-1394, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34476765

RESUMO

Chemical penetration enhancer (CPE) is a preferred approach to improve drug permeability through the skin, due to its unique advantages of simple use and high compatibility. However, CPEs efficiency and safety problems frequently arise, which greatly restrains the further application in transdermal drug delivery systems (TDDS). To get access to the root of problems, the efficiency and safety of CPEs are reviewed especially from molecular perspectives, which include (1) the possible factors of CPEs low efficiency; (2) the possible contribution of CPEs in the evolution of safety problems such as skin irritation and allergic reaction; (3) the interactive relationship between CPEs efficiency and safety, as well as the bottlenecks of achieving their balance. More importantly, based on these, recent advances are summarized in improving efficiency or safety of CPEs, which offers a guidance of rationally selecting CPEs in future research.


Assuntos
Absorção Cutânea , Pele , Administração Cutânea , Sistemas de Liberação de Medicamentos , Permeabilidade , Preparações Farmacêuticas/metabolismo , Pele/metabolismo
4.
AAPS PharmSciTech ; 22(4): 139, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33880664

RESUMO

Chemical enhancers (CEs) decreased the barrier of the stratum corneum (SC) to enhance drug permeation. This was a "dynamic" behavior, which involved three processes including passing in, acting on, and passing out of the SC. However, compared with mature "static" researches about acting on the SC, the other two processes were poorly understood. This work aimed to probe the dynamic behavior of CEs and modulate it for satisfactory effectiveness. The investigating method of CEs' dynamic behavior was established to obtain the rate of CEs passing in and out of the SC. An analysis attribution was conducted to obtain the possible reasons for the quite different dynamic behavior of CEs based on log P, solubility parameter, and minimum binging energy. It demonstrated the rate of CEs passing in and out of the SC was dependent on CE affinity with the SC and the interaction between CEs and the SC, respectively. The relevance between CEs' dynamic behavior and the extent of decreasing SC barrier was confirmed by transepidermal water loss (TEWL). The higher rate of CE passing in the SC and a lower rate of passing out of the SC may contribute to an increased concentration of CEs in the SC, leading to a stronger ability to decrease the SC barrier. More importantly, two biodegradable CEs (Leu-Dod and Ser-Dod) of dodecanol were synthesized and achieved a modulation of its dynamic behavior to obtain more satisfactory effectiveness of enhancing drug permeation. This work was meaningful for the guidance of rationally promoting CEs' effectiveness from a dynamic perspective, which was an unprecedented attempt in this field.


Assuntos
Absorção Cutânea , Pele/metabolismo , Materiais Biocompatíveis , Epiderme/metabolismo , Humanos , Solubilidade , Água/metabolismo
5.
Pharm Res ; 37(9): 169, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32794010

RESUMO

PURPOSE: Penetration enhancers (PEs) enhancing efficacy depends on two processes: PEs release from patches and action on skin. Compared with their action on skin, PEs release process was poorly understood. Therefore, the purpose of this study was to make a mechanistic understanding of PEs release from acrylic pressure-sensitive adhesive of patches and propose an unconventional enhancement of PEs efficacy. METHODS: PEs efficacy was evaluated both in drug permeation study and drug pharmacokinetic study. Confocal Raman spectroscopy was employed to observe PEs release behavior by mapping PEs dynamic distribution in skin. The mechanism of PEs release behavior was provided from molecular interaction and rheology using FT-IR, molecular docking, molecular dynamic simulation and rheometer, separately. RESULTS: The release behavior of PEs themselves greatly restricted their efficacy. By using PEG 400, an improvement of oleic acid (OA) release behavior was achieved, and the efficacy of OA was significantly enhanced with enhancing ratio (ER) from 2.69 to 4.10 and AUClast from 1574 ± 87 to 2664 ± 249 ng·h/mL, separately. The improvement of OA release behavior was primarily resulted from reduction of the interaction between OA and adhesive, which was caused by other small molecules with a strong ability in forming hydrogen bonds with adhesive. Also, the rigidity of adhesive was a factor in affecting PEs release behavior. CONCLUSIONS: An unconventional passive enhancement of transdermal drug delivery was achieved via improving PEs themselves releasing from acrylic pressure-sensitive adhesive. Graphical abstract Influence of PEs release behavior on drug permeation through skin and molecular mechanism.


Assuntos
Liberação Controlada de Fármacos/fisiologia , Absorção Cutânea/fisiologia , Adesivos/química , Administração Cutânea , Animais , Química Farmacêutica , Sistemas de Liberação de Medicamentos , Ácidos Graxos/química , Felodipino/administração & dosagem , Felodipino/farmacocinética , Masculino , Modelos Moleculares , Simulação de Acoplamento Molecular , Preparações Farmacêuticas/metabolismo , Ratos , Pele/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Adesivo Transdérmico
6.
Ther Deliv ; 3(3): 299-301, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22833990

RESUMO

"In order to increase the quality of transdermal drug-delivery systems, it [quality] must be built into the systemic product development".


Assuntos
Administração Cutânea , Sistemas de Liberação de Medicamentos , Humanos
7.
Pharm Res ; 20(1): 103-9, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12608543

RESUMO

PURPOSE: The purpose of this work was to characterize in vitro/in vivo delivery and pharmacokinetics of oxybutynin (OXY) and its active metabolite. N-desethyloxybutynin (DEO), by a novel matrix transdermal system (TDS). METHODS: Two in vivo, randomized, three-way crossover trials examined single/multiple OXY TDS doses. Abdomen, buttock, and hip application sites were compared and dose proportionality was evaluated. Model independent pharmacokinetics, elimination rate constants, and metabolite/drug ratios were derived from both plasma OXY and DEO concentrations. RESULTS: Single/multiple applications of the OXY TDS to the abdomen yielded mean Cmax OXY concentrations of 3.4 +/- 1.1/6.6 +/- 2.4 ng/mL and median tmax of 36/10 h, with steady state achieved during the second application. Plasma OXY and DEO concentrations decreased gradually after Cmax until system removal. Buttock and hip applications resulted in bioequivalent OXY absorption. AUC ratios of DEO/OXY were 1.5 +/- 0.4 (single dose) and 1.3 +/- 0.3 (multiple dose). Mean in vitro OXY skin absorption (186 microg/h) was comparable to the estimated in vivo delivery (163 microg/h) over 96 h. CONCLUSIONS: Sustained delivery over 4 days and multiple sites allow a convenient, well-tolerated, twice-weekly OXY TDS dosing. A low incidence of anticholinergic side effects is expected during clinical use because of the avoidance of presystemic metabolism and low DEO plasma concentrations. The consistent delivery, absorption, and pharmacokinetics should result in an effective treatment of patients with overactive bladder.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Ácidos Mandélicos/administração & dosagem , Ácidos Mandélicos/farmacocinética , Administração Cutânea , Adulto , Idoso , Área Sob a Curva , Intervalos de Confiança , Estudos Cross-Over , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/metabolismo , Preparações de Ação Retardada/farmacocinética , Feminino , Humanos , Masculino , Ácidos Mandélicos/metabolismo , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...