Search results for "PERMEABILITY"
showing 10 items of 596 documents
Functional feature of a novel model of blood brain barrier: Studies on permeation of test compounds
2001
Drug delivery to the central nervous system (CNS) is subject to the permeability limitations imposed by the blood-brain barrier (BBB). Several systems in vitro have been described to reproduce the physical and biochemical behavior of intact BBB, most of which lack the feature of the in vivo barrier. We developed a fully formed monolayer of RBE4.B immortalized rat brain microvessel endothelial cells (ECs), grown on top of polycarbonate filter inserts with cortical neuronal cells grown on the outside. Neurons induce ECs to synthesize and sort occludin to the cell periphery. Occludin localization is regulated by both compositions of the substratum and soluble signals released by cortical co-cu…
Studies on a new potential dopaminergic agent: in vitro BBB permeability, in vivo behavioural effects and molecular docking evaluation.
2015
2-Amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-PHEN) has been previously synthesized to obtain a potential prodrug capable of release dopamine (DA) into CNS. However, DA-PHEN could act per se as a dopaminergic drug. In this study, the permeability transport (Pe), obtained by parallel artificial permeability assay (PAMPA), indicated a low passive transcellular transport (Pe = 0.32 ± 0.01 × 10(-6 )cm/s). Using the Caco-2 cell system, the Papp AP-BL in absorptive direction (3.36 ± 0.02 × 10(-5 )cm/s) was significantly higher than the Papp BL-AP in secretive direction (1.75 ± 0.07 × 10(-5 )cm/s), suggesting a polarized transport. The efflux ratio (Papp AP-BL/Papp BL-AP = 0…
Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Sitagliptin Phosphate Monohydrate
2021
Sitagliptin is an antihyperglycemic drug used in adults for the treatment of diabetes Type 2. Literature data and in-house experiments were applied in this monograph to assess whether methods based on the Biopharmaceutics Classification System (BCS) could be used to assess the bioequivalence of solid immediate-release (IR) oral dosage forms containing sitagliptin phosphate monohydrate, as an alternative to a pharmacokinetic study in human volunteers. The solubility and permeability characteristics of sitagliptin were reviewed according to the BCS, along with dissolution, therapeutic index, therapeutic applications, pharmacokinetics, pharmacodynamic characteristics, reports of bioequivalence…
Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Ketoprofen
2012
Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing ketoprofen are reviewed. Ketoprofen's solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability (BA)/dissolution data were taken into consideration. The available data suggest that according to the current Biopharmaceutics Classification System (BCS) and all current guidances, ketoprofen is a weak acid that would be assigned to BCS Class II. The extent of ketoprofen abso…
Evaluation of the pH effect of formulations on the skin permeability of drugs by biopartitioning micellar chromatography☆
2004
Dermal absorption of chemicals is an area of increasing interest for the pharmaceutical and cosmetic industries, as well as in dermal exposure and risk assessment processes. Biopartitioning micellar chromatography (BMC) is a mode of reversed phase micellar chromatography that has proved to be useful in the description and prediction of several pharmacological properties of xenobiotics including oral drug absorption, ocular and skin drug permeability. The present paper deals with the application of biopartitionig micellar chromatography to evaluate the pH effect on the skin permeability of twelve non-steroidal anti-inflammatory drugs and lidocaine. For this purpose the BMC retention of the w…
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Levetiracetam.
2015
Literature and experimental data relevant for the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing levetiracetam are reviewed. Data on solubility and permeability suggest that levetiracetam belongs to class I of the biopharmaceutical classification system (BCS). Levetiracetam's therapeutic use, its wide therapeutic index, and its favorable pharmacokinetic properties make levetiracetam a valid candidate for the BCS-based biowaiver approach. Further, no BE studies with levetiracetam IR formulations in which the test formulation failed to show BE with the comparator have been reported in the open lit…
Intestinal drug efflux: formulation and food effects
2001
The intestine, primarily regarded as an absorptive organ, is also prepared for the elimination of certain organic acids, bases and neutral compounds depending on their affinity to intestinal carrier systems. Several of the transport systems known to mediate efflux in the major clearing organs--liver and kidney--are also expressed in the intestine. Examples of secretory transporters in the intestine are P-glycoprotein, members of the multidrug resistance associated protein family, breast cancer resistance protein, organic cation transporters and members of the organic anion polypeptide family. In this communication, the P-glycoprotein mediated intestinal secretion of talinolol, a model compo…
Amphiphilic HPMA-LMA copolymers increase the transport of Rhodamine 123 across a BBB model without harming its barrier integrity.
2012
Abstract The successful non-invasive treatment of diseases associated with the central nervous system (CNS) is generally limited by poor brain permeability of various developed drugs. The blood–brain barrier (BBB) prevents the passage of therapeutics to their site of action. Polymeric drug delivery systems are promising solutions to effectively transport drugs into the brain. We recently showed that amphiphilic random copolymers based on the hydrophilic p(N-(2-hydroxypropyl)-methacrylamide), pHPMA, possessing randomly distributed hydrophobic p(laurylmethacrylate), pLMA, are able to mediate delivery of domperidone into the brain of mice in vivo. To gain further insight into structure–propert…
Drug gastrointestinal absorption in rat: Strain and gender differences.
2015
Predictive animal models of intestinal drug absorption are essential tools in drug development to identify compounds with promising biopharmaceutical properties. In situ perfusion absorption studies are routinely used in the preclinical setting to screen drug candidates. The objective of this work is to explore the differences in magnitude and variability on intestinal absorption associated with rat strain and gender. Metoprolol and Verapamil absorption rate coefficients were determined using the in situ closed loop perfusion model in four strains of rats and in both genders. Strains used were Sprague-Dawley, Wistar-Han, Wistar-Unilever, Long-Evans and CD∗IGS. In the case of Metoprolol only…
Biowaiver monographs for immediate-release solid oral dosage forms: Zidovudine (azidothymidine).
2012
Literature data on the properties of zidovudine relevant to waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate-release (IR) solid oral dosage forms containing zidovudine alone or in combination with other active pharmaceutical ingredients (APIs) are reviewed. Solubility, dissolution, and permeability data for zidovudine, along with its dosing schedule, therapeutic index and pharmacokinetic properties, and reports related to BE/bioavailability were all taken into consideration. Data for solubility and permeability suggest that zidovudine belongs to Class I according to the Biopharmaceutics Classification System. Also, zidovudine is not a narrow therapeut…