Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Eur J Pharm Sci ; 192: 106655, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38016626

RESUMO

Hot-melt extrusion is often used to prepare amorphous solid dispersion to overcome low drug solubility and enhance bio-performance of the formulation. Due to the uniqueness of each drug - polymer combination and its physico-chemical properties, setting the appropriate HME barrel temperature, feed rate and screw speed ensures drug amorphization, absence of residual crystallinity, absence of water, and a suitable drug release profile. In this research, samples with BCS II/IV model drug and PVP/VA polymer were prepared to evaluate the impact of HME process parameters, incoming drug form (anhydrous vs. hydrate), and drug supplier (i.e., impurity profile), on biorelevant drug release. This study provides a relationship between observed in vitro supersaturation and precipitation behavior of amorphous solid dispersion formulation with in vivo results, on patients, by using the acceptor profile of side-by-side dissolution-permeation apparatus. An in vitro dissolution method, in small volumes, in an apparatus with paddles and dissolution-permeation side-by-side method was developed on the MicroFlux™ apparatus to assess if the differences observed in vitro bears relevance to the bioequivalence outcome in vivo. The former was used to guide the generic drug product development due to high discriminatory strength, while the latter was biorelevant, due to the inclusion of the second compartment assuring absorptive environment to capture the impact of supersaturation and subsequent precipitation on bioavailability. Bio-relevancy of the in vitro method was confirmed with the in vivo dog study and clinical study on patients, and an in vitro - in vivo correlation was established. For the investigated BCS II/IV drug, this research highlights the importance of considering supersaturation and formation of colloidal species during amorphous solid dispersion release testing to assure product quality, safety and efficacy.


Assuntos
Contaminação de Medicamentos , Temperatura Alta , Humanos , Animais , Cães , Polímeros/química , Polivinil/química , Solubilidade , Liberação Controlada de Fármacos , Composição de Medicamentos/métodos
2.
J Pharm Sci ; 112(7): 1749-1762, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37142122

RESUMO

The workshop "Drug Permeability - Best Practices for Biopharmaceutics Classification System (BCS) Based Biowaivers" was held virtually on December 6, 2021, organized by the University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI), and the Food and Drug Administration (FDA). The workshop focused on the industrial, academic, and regulatory experiences in generating and evaluating permeability data, with the aim to further facilitate implementation of the BCS and efficient development of high-quality drug products globally. As the first international permeability workshop since the BCS based biowaivers was finalized as the ICH M9 guideline, the workshop included lectures, panel discussions, and breakout sessions. Lecture and panel discussion topics covered case studies at IND, NDA, and ANDA stages, typical deficiencies relating to permeability assessment supporting BCS biowaiver, types of evidence that are available to demonstrate high permeability, method suitability of a permeability assay, impact of excipients, importance of global acceptance of permeability methods, opportunities to expand the use of biowaivers (e.g. non-Caco-2 cell lines, totality-of-evidence approach to demonstrate high permeability) and future of permeability testing. Breakout sessions focused on 1) in vitro and in silico intestinal permeability methods; 2) potential excipient effects on permeability and; 3) use of label and literature data to designate permeability class.


Assuntos
Biofarmácia , Relatório de Pesquisa , Preparações Farmacêuticas , Biofarmácia/métodos , Equivalência Terapêutica , Excipientes , Permeabilidade , Solubilidade
3.
Pharmazie ; 67(6): 518-24, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22822540

RESUMO

Curcumin, a principal component from Curcuma longa, with antioxidant and anti-inflammatory activities was proposed as a potential candidate for the preventation and/or treatment of cancer and chronic diseases. However, curcumin could not achieve its expected therapeutic outcome in clinical trials due to its low solubility and poor bioavailability. The actual intestinal physiological barriers limiting curcumin absorption after oral administration have not been fully investigated. To identify the main barriers curtailing its absorption, in vitro permeability of curcumin and flux of its glucuronide were monitored in rat jejunum and Transwell grown Caco-2 cells. Curcumin was more permeable under acidic conditions, but the permeability was substantially below the permeability of highly permeable standards. Its efflux could not be inhibited by specific Pgp and MRP inhibitors. BCRP was found to participate in curcumin transport, but the Organic Anion Transporting Polypeptide (OATP) did not. The permeability of curcumin significantly increased when the structure of mucus was compromised. The inhibitor of curcumin metabolism, piperin, failed to act as a permeability enhancer. Piperin inhibited Pgp and MRP transporters and decreased the amount of glucuronide transported back into the intestine. Inclusion of piperin in curcumin-containing formulations is highly recommended as to inhibit curcumin glucuronidation and to increase the transport of formed glucuronides into the plasma, therefore increasing the probability of glucuronide distribution into target tissue and inter-convertion to curcumin. It would also be beneficial, if curcumin delivery systems could reversibly compromise the mucous integrity to minimize the non-specific binding of curcumin to its constituents.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacocinética , Algoritmos , Alcaloides/farmacologia , Animais , Benzodioxóis/farmacologia , Soluções Tampão , Células CACO-2 , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Glucuronídeos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Absorção Intestinal , Mucosa Intestinal/metabolismo , Jejuno/metabolismo , Espectrometria de Massas , Potenciais da Membrana/efeitos dos fármacos , Técnicas de Patch-Clamp , Permeabilidade , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Ratos , Solubilidade
4.
Int J Pharm ; 388(1-2): 151-8, 2010 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-20060454

RESUMO

The primary goal of this study was to formulate Ca-pectinate microcapsules with self-microemulsifying core to enhance the solubility and permeability of BCS class IV drug furosemide. An Inotech IE-50R encapsulator equipped with a concentric nozzle was utilized to transform liquid self-microemulsifying system (SMES) to solid microcapsules. Self-microemulsifying core was optimized with respect to drug loading capacity and encapsulation efficiency and evaluated for its impact on furosemide permeability through rat small intestine and Caco-2 cell monolayers. Retention of the core phase was considerably improved (up to 70-80%) by optimization of the SMES and microcapsules' drying process. Incorporation of furosemide in self-microemulsifying core of microcapsules resulted in improved permeability and drug release characteristics in comparison to microspheres (without SMES in the core). The obtained results illustrate the prospective use of microcapsules with self-microemulsifying core for the delivery of compounds with poor biopharmaceutical properties via the oral route.


Assuntos
Excipientes/química , Furosemida/administração & dosagem , Pectinas/química , Animais , Células CACO-2 , Cápsulas , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos , Emulsões , Furosemida/química , Furosemida/farmacocinética , Humanos , Absorção Intestinal , Masculino , Microesferas , Ratos , Ratos Wistar , Solubilidade
5.
Pharmazie ; 62(4): 318-20, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17484293

RESUMO

Although a clinically relevant interaction between a fluoroquinolone and a metal cation was first described more than 20 years ago the biopharmaceutical mechanism of this interaction is still not understood. One of the obvious disagreements in the literature is about the effect of metal cations on the solubility of fluoroquinolones. Namely, metal cations are reported to increase the solubility of fluoroquinolones as well as to decrease it and thus cause the lowered bioavailability. Thus in this work the solubility of ciprofloxacin, norfloxacin and ofloxacin and the effect of metal cations on the solubility of these fluoroquinolones in aqueous media of different pH values were reevaluated. The results clearly show that the metal cations either do not affect or even increase the solubility of fluoroquinolones. Thus they surely do not influence the bioavailability of these drugs by decreasing their solubility. Additionally, possible explanations for the contradictory results reported in the literature are given.


Assuntos
Fluoroquinolonas/química , Metais/química , Antibacterianos/química , Disponibilidade Biológica , Biofarmácia , Cátions , Fenômenos Químicos , Físico-Química , Ciprofloxacina/química , Concentração de Íons de Hidrogênio , Solubilidade , Espectrofotometria Ultravioleta
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...