共查询到20条相似文献,搜索用时 46 毫秒
1.
Thiago da Silva Honório Eduardo Costa Pinto Helvécio Vinicius A. Rocha Valeria Sant’Anna Dantas Esteves Tereza Cristina dos Santos Helena Carla Rangel Castro Carlos Rangel Rodrigues Valeria Pereira de Sousa Lucio Mendes Cabral 《AAPS PharmSciTech》2013,14(3):1244-1254
The aim of the present work was to use GastroPlus™ software for the prediction of pharmacokinetic profiles and in vitro–in vivo correlation (IVIVC) as tools to optimize the development of new generic medications. GastroPlus™ was used to simulate the gastrointestinal compartment and was based on the advanced compartmental absorption and transit model. Powder dissolution and efavirenz tablet dissolution studies were carried out to generate data from which correlation was established. The simulated plasma profile, based on the physicochemical properties of efavirenz, was almost identical to that observed in vivo for biobatches A and B. A level A IVIVC was established for the dissolution method obtained for the generic candidate using the Wagner–Nelson (r2 = 0.85) and for Loo–Riegelman models (r2 = 0.92). The percentage of fraction absorbed indicated that 0.5% sodium lauryl sulfate may be considered a biorelevant dissolution medium for efavirenz tablets. The simulation of gastrointestinal bioavailability and IVIVC obtained from immediate-release tablet formulations suggests that GastroPlus™ is a valuable in silico method for IVIVC and for studies directed at developing formulations of class II drugs.KEY WORDS: bioavailability, computational simulation, efavirenz, GastroPlus™, in vivo–in vitro correlation 相似文献
2.
The present study was aimed to predict the absorption profile of a risperidone immediate release tablet (IR) and to develop the level A in vitro–in vivo correlation (IVIVC) of the drug using the gastrointestinal simulation based on the advanced compartmental absorption and transit model implemented in GastroPlus™. Plasma concentration data, physicochemical, and pharmacokinetic properties of the drug were used in building its absorption profile in the gastrointestinal tract. Since the fraction absorbed of risperidone in simulation was more than 90% with low water solubility, the drug met the criteria of class II of the Biopharmaceutics Classification System. The IVIVC was developed based on the model built using the plasma data and the in vitro dissolution data in several dissolution media based on the Japanese Guideline for Bioequivalence Studies of Generic Products. The gastrointestinal absorption profile of risperidone was successfully predicted. A level A IVIVC was also successfully developed in all dissolution media with percent prediction error for Cmax and the area under the curve less than 10% for both reference and test drug.Key words: GastroPlus™, immediate release tablet, in vitro–in vivo correlation, risperidone 相似文献
3.
Katja Berginc Nata?a ?kalko-Basnet Purusotam Basnet Albin Kristl 《AAPS PharmSciTech》2012,13(4):1045-1053
Vaginal administration is a promising alternative to the per-oral route in achieving systemic or local therapeutic effects, when intestinal drug absorption is hindered by problematic biopharmaceutical drug properties. The aim of this study was to establish an in vitro vaginal model and use it to characterize biopharmaceutical properties of liposomally associated curcumin destined for vaginal delivery. The in vitro permeability, metabolism, and tissue retention of high/low permeable compounds were assessed on cow vaginal mucosa and compared to the permeabilities determined through Caco-2 cells and rat jejunum in vitro. The results showed that the intestinal mucosa was superior to the vaginal one in categorizing drugs based on their permeabilities in high/low permeable classes. Passive diffusion was found to be the main mechanism of drug penetration through vaginal mucosa and it was not affected by transporter–enzyme alliance, as their expression/activity was significantly reduced compared to the intestinal tract. Curcumin permeability from the solution form was the lowest of all tested substances due to its significant tissue retention and curcumin–mucus interactions. The permeability of liposomally associated curcumin was even lower but the binding of liposomally associated curcumin to the vaginal tissue was significantly higher. The permeability and tissue retention of liposomal curcumin were vesicle size dependent. Vaginal application of liposomally associated curcumin provides relatively high levels of curcumin in vaginal tissue, with limited systemic absorption.KEY WORDS: curcumin, intestinal models, liposomes, permeability, vaginal mucosa 相似文献
4.
Ashutosh K. Dash Debaraj Mukherjee Abhijeet Dhulap Saqlain Haider Deepak Kumar 《Bioorganic & medicinal chemistry letters》2019,29(24):126750
A green chemistry approach has been developed for the synthesis of chromene dihydropyrimidinone (CDHPM) using recyclable Fe/Al pillared clay catalyst. Pharmacokinetic parameters like aqueous solubility, lipophilicity, P-glycoprotein (P-gp) ATPase activity, permeability, plasma protein binding, red blood cell (RBC) partitioning, metabolic stability in liver microsomes and in silico computations have been studied for the most potent anticancer chromene dihydropyrimidinone hybrid 1. This compound exhibited low solubility, optimum lipophilicity, no P-gp inhibitory activity, intermediate permeability, high plasma protein binding, low RBC partitioning, acceptable metabolic stability in rat liver microsomes (RLM) as well as human liver microsomes (HLM) with transitional hepatic extraction ratio. 相似文献
5.
Polyamines decrease the permeability of the outer membrane of Escherichia coli to fluoroquinolones and β-lactams. In this study, we tested the effect of four polyamines (spermidine, spermine, cadaverine and putrescine) on fluoroquinolone uptake in Mycobacterium bovis BCG. Our results show that polyamines are also capable of reducing the permeability of the mycobacterial outer membrane to fluoroquinolones. Spermidine was most effective and demonstrated reversible dose- and pH-dependent inhibition of ciprofloxacin accumulation. The extent of this inhibition was demonstrated across the fluoroquinolone compound class to varying degrees. Furthermore, we have shown that the addition of spermidine increases the survival of M. bovis BCG after a 5-day exposure to ciprofloxacin by up to 25 times. The treatment of actively-replicating Mycobacterium tuberculosis with spermidine reduced ciprofloxacin accumulation by half while non-replicating nutrient-starved M. tuberculosis cultures lacked similar sensitivity to polyamines. Gene expression studies showed that several outer membrane proteins are significantly down–regulated during the shift to non–replication. Collectively, these characteristics of fluoroquinolone uptake in M. bovis BCG are consistent with facilitated transport by porin-like proteins and suggest that a reduction in intracellular uptake contributes to the phenotypic drug resistance demonstrated by M. tuberculosis in the non-replicating state. 相似文献
6.
A novel drug-in-adhesive matrix was designed and prepared. A thermoplastic elastomer, styrene–isoprene–styrene (SIS) block copolymer, in combination with tackifying resin and plasticizer, was employed to compose the matrix. Capsaicin was selected as the model drug. The drug percutaneous absorption, adhesion properties, and skin irritation were investigated. The results suggested that the diffusion through SIS matrix was the rate-limiting step of capsaicin percutaneous absorption. [SI] content in SIS and SIS proportions put important effects on drug penetration and adhesion properties. The chemical enhancers had strong interactions with the matrix and gave small effect on enhancement of drug skin permeation. The in vivo absorption of samples showed low drug plasma peaks and a steady and constant plasma level for a long period. These results suggested that the possible side effects of drug were attenuated, and the pharmacological effects were enhanced with an extended therapeutic period after application of SIS matrix. The significant differences in pharmacokinetic parameters produced by different formulations demonstrated the influences of SIS copolymer on drug penetrability. Furthermore, the result of skin toxicity test showed that no skin irritation occurred in guinea pig skin after transdermal administration of formulations.Key words: adhesion, in vivo absorption, skin irritation, thermoplastic elastomer, transdermal drug delivery 相似文献
7.
Jerome K. Geroge Priya Ranjan Prasad Verma Jayachandran Venkatesan Jin-Young Lee Dong-Han Yoon Se-Kwon Kim Sandeep Kumar Singh 《AAPS PharmSciTech》2017,18(8):2871-2888
The present study aimed for in vitro-in vivo-in silico simulation studies of experimentally designed (32-factorial) Capmul PG-8-cored, Eudragit RSPO-Lutrol F 127 nanocapsules to ferry felodipine using GastroPlus?. The in silico parameter sensitivity analysis for pharmacokinetic parameters was initially assessed to justify the preparation of felodipine-loaded nanocapsules (FLNs) with enhanced solubility to overcome the bioavailability issues of felodipine. The overall integrated desirability ranged between 0.8187 and 0.9488 for three optimized FLNs when analyzed for mean particle size, zeta potential, encapsulation efficiency, and in vitro dissolution parameters. The morphological evaluation (SEM, TEM, and AFM) demonstrated spherical nanoparticles (200–300 nm). Validated LC-MS/MS analysis demonstrated enhanced relative bioavailability (13.37-fold) of optimized FLN as compared to suspension. The simulated regional absorption of the FLN presented significant absorption from the cecum (26.3%) and ascending colon (20.1%) with overall absorption of 67.4% from the GIT tract. Furthermore, in vitro-in vivo correlation demonstrated the Wagner-Nelson method as the preferred model as compared to mechanistic and numerical deconvolution on the basis of least mean absolute prediction error, least standard error of prediction, least mean absolute error, and maximum correlation coefficient (r 2 = 0.920). The study demonstrated enhanced oral absorption of felodipine-loaded nanocapsules, and GastroPlus? was found to be an efficient simulation tool for in vitro-in vivo-in silico simulations. 相似文献
8.
The parallel artificial membrane permeation assay (PAMPA) was developed as a model for the prediction of transcellular permeation in the process of drug absorption. Our research group has measured the PAMPA permeability of peptide‐related compounds, diverse drugs, and agrochemicals. This work led to a classical quantitative structure–activity relationship (QSAR) equation for PAMPA permeability coefficients of structurally diverse compounds based on simple physicochemical parameters such as lipophilicity at a particular pH (log Poct and |pKa?pH|), H‐bond acceptor ability (SAHA), and H‐bond donor ability (SAHD). Since the PAMPA permeability of lipophilic compounds decreased with their apparent lipophilicity due to the unstirred water layer (UWL) barrier on membrane surfaces and to membrane retention, a bilinear QSAR model was introduced to explain the permeability of a broader set of compounds using the same physicochemical parameters as those used for the linear model. We also compared PAMPA and Caco‐2 cell permeability coefficients of compounds transported by various absorption mechanisms. The compounds were classified according to their absorption pathway (passively transported compounds, actively transported compounds, and compounds excreted by efflux systems) in the plot of Caco‐2 vs. PAMPA permeability. Finally, based on the QSAR analyses of PAMPA permeability, an in silico prediction model of human oral absorption for possibly transported compounds was proposed, and the usefulness of the model was examined. 相似文献
9.
K. Karthikeyan Ezhilarasan Vijayalakshmi Purna Sai Korrapati 《AAPS PharmSciTech》2014,15(5):1172-1180
In this study, we have evaluated the interactions of zein microspheres with different class of drugs (hydrophobic, hydrophilic, and amphiphilic) using in vitro and in silico analysis. Zein microspheres loaded with aceclofenac, metformin, and promethazine has been developed by solvent evaporation technique and analyzed for its compatibility. The physical characterization depicted the proper encapsulation of hydrophobic drug in the microspheres. The in vitro release study revealed the sustaining ability of the microspheres in the following order: hydrophobic > hydrophilic > amphiphilic. In silico analysis also confirmed the better binding affinity and greater interactions of hydrophobic drug with zein. The above results revealed that zein is more suitable for hydrophobic drugs in the development of sustained drug delivery systems using solvent evaporation technique. The study therefore envisages a scope for identifying the most suitable polymer for a sustained drug delivery system in accordance with the nature of the drug.KEY WORDS: hydrophilic drugs, hydrophobic drugs, in silico analysis, protein-drug interactions, solvent evaporation, zein microspheres 相似文献
10.
Hefei Zhang Binfeng Xia Jennifer Sheng Tycho Heimbach Tsu-Han Lin Handan He Yanfeng Wang Steven Novick Ann Comfort 《AAPS PharmSciTech》2014,15(2):400-406
Physiologically based pharmacokinetic (PBPK) modeling has been broadly used to facilitate drug development, hereby we developed a PBPK model to systematically investigate the underlying mechanisms of the observed positive food effect of compound X (cpd X) and to strategically explore the feasible approaches to mitigate the food effect. Cpd X is a weak base with pH-dependent solubility; the compound displays significant and dose-dependent food effect in humans, leading to a nonadherence of drug administration. A GastroPlus Opt logD Model was selected for pharmacokinetic simulation under both fasted and fed conditions, where the biopharmaceutic parameters (e.g., solubility and permeability) for cpd X were determined in vitro, and human pharmacokinetic disposition properties were predicted from preclinical data and then optimized with clinical pharmacokinetic data. A parameter sensitivity analysis was performed to evaluate the effect of particle size on the cpd X absorption. A PBPK model was successfully developed for cpd X; its pharmacokinetic parameters (e.g., C max, AUCinf, and t max) predicted at different oral doses were within ±25% of the observed mean values. The in vivo solubility (in duodenum) and mean precipitation time under fed conditions were estimated to be 7.4- and 3.4-fold higher than those under fasted conditions, respectively. The PBPK modeling analysis provided a reasonable explanation for the underlying mechanism for the observed positive food effect of the cpd X in humans. Oral absorption of the cpd X can be increased by reducing the particle size (<100 nm) of an active pharmaceutical ingredient under fasted conditions and therefore, reduce the cpd X food effect correspondingly. 相似文献
11.
The objective of this study was to investigate the relationship between in vitro permeability (Papp) values obtained from isolated nasal tissues and the absorption rates (ka) of the same compounds following nasal administration in animals and humans. The Papp of a set of 11 drug compounds was measured using animal nasal explants and plasma time–concentration profiles for each of the same compounds following intravenous (IV) and intranasal (IN) administration were experimentally determined or obtained from literature reports. The plasma clearance was estimated from the IV plasma time–concentration profiles, and ka was determined from the IN plasma time–concentration profiles using a deconvolution approach. The level of correlation between Papp and ka was established using Pearson correlation analysis. A good correlation (r = 0.77) representing a point-to-point relationship for each of the compounds was observed. This result indicates that the nasal absorption for many drug candidates can be estimated from a readily measured in vitro Papp value.Key words: bioavailability, drug transport, nasal administration, nasal mucosa, permeability 相似文献
12.
The aim of this article was to construct a T–ϕ phase diagram for a model drug (FD) and amorphous polymer (Eudragit® EPO) and to use this information to understand the impact of how temperature–composition coordinates influenced the final properties of the extrudate. Defining process boundaries and understanding drug solubility in polymeric carriers is of utmost importance and will help in the successful manufacture of new delivery platforms for BCS class II drugs. Physically mixed felodipine (FD)–Eudragit® EPO (EPO) binary mixtures with pre-determined weight fractions were analysed using DSC to measure the endset of melting and glass transition temperature. Extrudates of 10 wt% FD–EPO were processed using temperatures (110°C, 126°C, 140°C and 150°C) selected from the temperature–composition (T–ϕ) phase diagrams and processing screw speed of 20, 100 and 200rpm. Extrudates were characterised using powder X-ray diffraction (PXRD), optical, polarised light and Raman microscopy. To ensure formation of a binary amorphous drug dispersion (ADD) at a specific composition, HME processing temperatures should at least be equal to, or exceed, the corresponding temperature value on the liquid–solid curve in a F–H T–ϕ phase diagram. If extruded between the spinodal and liquid–solid curve, the lack of thermodynamic forces to attain complete drug amorphisation may be compensated for through the use of an increased screw speed. Constructing F–H T–ϕ phase diagrams are valuable not only in the understanding drug–polymer miscibility behaviour but also in rationalising the selection of important processing parameters for HME to ensure miscibility of drug and polymer.KEY WORDS: DSC, Flory–Huggins theory, hot-melt extrusion, thermal processing 相似文献
13.
Han vandeWaterbeemd 《化学与生物多样性》2009,6(11):1760-1766
Many compounds entering clinical studies do not survive the numerous hurdles for a good pharmacological lead to a drug on the market. The reasons for attrition have been widely studied which resulted in more early attention to compound quality related to physical chemistry, drug metabolism and pharmacokinetics (DMPK), and toxicology/safety. This paper will briefly review current physicochemical in vitro assays and in silico predictions to support compound and library design through to lead optimization. The most important physicochemical properties include lipophilicity (log P/D), pKa, solubility, and permeability. These drive key ADMET properties such as absorption, cell penetration, access to the brain, volume of distribution, plasma protein binding, metabolism, and toxicity, as well as biopharmaceutical behavior. Much data are now available from medium‐ to high‐throughput physchem and ADMET in vitro assays, either in the public domain (see, e.g., PubChem, PubMed) or in drug companies' in‐house databases. Such data are increasingly being computer‐modelled and used in predictive chemistry. New pipelining technology makes it easier to build and update QSAR models so that such models can use the latest available data to produce robust local and global predictive in silico ADMET models. 相似文献
14.
Ravi D. Vaishya Mitan Gokulgandhi Sulabh Patel Mukul Minocha Ashim K. Mitra 《AAPS PharmSciTech》2014,15(5):1238-1251
Development and characterization of dexamethasone (DEX)-encapsulated polymeric nanomicelles have been reported. A low molecular weight di-block copolymer was synthesized and characterized for its structure, molecular weights, critical micelle concentration (CMC), and cytotoxicity in ocular cells. In order to delineate the effects of drug–polymer interactions on drug solubilization in micelle core, a response surface methodology was generated with the help of SAS 9.02 (exploratory model). The method for preparing micelle was modified based on the results obtained from exploratory model. The formulation was optimized by response surface methodology (optimization model) to achieve DEX solubility of above 1 mg/mL. The optimized formulation was characterized for DEX solubility, nanomicelle size, polydispersity index, surface morphology, in vitro transport across conjunctival cell line, and ex vivo transport across excised rabbit sclera. Nanomicelles exhibited average sizes in range of 25–30 nm with unimodel size distribution and low polydispersity of 0.125. Nanomicelles increased DEX permeability by 2 times across conjunctival cell line and by 2.5 times across the excised rabbit sclera as compared to DEX suspension. A design of experiment (DOE) strategy was successfully applied to understand the effects of drug–polymer interaction on drug solubility. DOE was also employed to achieve optimal formulation with high DEX solubility. Nanomicellar formulation significantly enhanced DEX permeability across the excised rabbit sclera. Therefore, nanomicellar formulation may provide therapeutic levels in the back of the eye following topical administration. 相似文献
15.
We have determined the X-ray structure of the complex between the DNA quadruplex d(5′-GGGG-3′)4 and daunomycin, as a potential model for studying drug–telomere interactions. The structure was solved at 1.08 Å by direct methods in space group I4. The asymmetric unit comprises a linear arrangement of one d(GGGG) strand, four daunomycin molecules, a second d(GGGG) strand facing in the opposite direction to the first, and Na and Mg cations. The crystallographic 4-fold axis generates the biological unit, which is a 12-layered structure comprising two sets of four guanine layers, with four layers each of four daunomycins stacked between the 5′ faces of the two quadruplexes. The daunomycin layers fall into two groups which are novel in their mode of self assembly. The only contacts between daunomycin molecules within any one of these layers are van der Waals interactions, however there is substantial π–π stacking between successive daunomycin layers and also with adjacent guanine layers. The structure differs significantly from all other parallel d(TGGGGT)4 quadruplexes in that the 5′ guanine adopts the unusual syn glycosyl linkage, refuting the widespread belief that such conformations should all be anti. In contrast to the related d(TGGGGT)/daunomycin complex, there are no ligand–quadruplex groove insertion interactions. 相似文献
16.
Jin Wang Ruimiao Chang Yanan Zhao Jiye Zhang Ting Zhang Qiang Fu Chun Chang Aiguo Zeng 《AAPS PharmSciTech》2017,18(7):2541-2550
Coamorphous systems using citric acid as a small molecular excipient were studied for improving physical stability and bioavailability of loratadine, a BCS class II drug with low water solubility and high permeability. Coamorphous loratadine-citric acid systems were prepared by solvent evaporation technique and characterized by differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy. Solid-state analysis proofed that coamorphous loratadine-citric acid system (1:1) was amorphous and homogeneous, had a higher T g over amorphous loratadine, and the intermolecular hydrogen bond interactions between loratadine and citric acid exist. The solubility and dissolution of coamorphous loratadine-citric acid system (1:1) were found to be significantly greater than those of crystalline and amorphous form. The pharmacokinetic study in rats proved that coamorphous loratadine-citric acid system (1:1) could significantly improve absorption and bioavailability of loratadine. Coamorphous loratadine-citric acid system (1:1) showed excellently physical stability over a period of 3 months at 25°C under 0% RH and 25°C under 60% RH conditions. The improved stability of coamorphous loratadine-citric acid system (1:1) could be related to an elevated T g over amorphous form and the intermolecular hydrogen bond interactions between loratadine and citric acid. These studies demonstrate that the developed coamorphous loratadine-citric acid system might be a promising oral formulation for improving solubility and bioavailability of loratadine. 相似文献
17.
Nikhil Malewar Makarand Avachat Varsha Pokharkar Shirish Kulkarni 《AAPS PharmSciTech》2013,14(3):1178-1189
The purpose of the present study was to control in vitro burst effect of the highly water-soluble drug, ropinirole hydrochloride to reduce in vivo dose dumping and to establish in vitro–in vivo correlation. The pharmacokinetics of two entirely different tablet formulation technologies is also explored in this study. For pharmacokinetics study, FDA recommends at least 10% difference in drug release for formulations to be studied but here a different approach was adopted. The formulations F8A and F9A having similar dissolution profiles among themselves and with Requip® XL™ (f2 value 72, 77, 71 respectively) were evaluated. The Cmax of formulation F8A comprising hypromellose 100,000 cP was 1005.16 pg/ml as compared to 973.70 pg/ml of formulation F9A comprising hypromellose 4000 cP irrespective of Tmax of 5 and 5.75 h, respectively. The difference in release and extent of absorption in vivo was due to synergistic effect of complex RH release mechanism; however, AUC0–t and AUC0–∞ values were comparable. The level A correlation using the Wagner–Nelson method supported the findings where R2 was 0.7597 and 0.9675 respectively for formulation F8A and F9A. Thus, in vivo studies are required for proving the therapeutic equivalency of different formulation technologies even though f2 ≥ 50. The technology was demonstrated effectively at industrial manufacturing scale of 200,000 tablets.KEY WORDS: controlled release polymer, in vitro–in vivo correlation (IVIVC), multiple barrier layer tablets, pharmacokinetics, ropinirole hydrochloride (RH) 相似文献
18.
Oluwatoyin A. Adeleke Yahya E. Choonara Pradeep Kumar Lisa C. du Toit Lomas K. Tomar Charu Tyagi Viness Pillay 《AAPS PharmSciTech》2013,14(4):1349-1359
Drug release from hydrophilic matrices is regulated mainly by polymeric erosion, disentanglement, dissolution, swelling front movement, drug dissolution and diffusion through the polymeric matrix. These processes depend upon the interaction between the dissolution media, polymeric matrix and drug molecules, which can be significantly influenced by formulation variables and excipients. This study utilized mathematical parameters to evaluate the impacts of selected formulation variables and various excipients on the release performance of hydrophilic polyamide 6,10 (PA 6,10) monolithic matrix. Amitriptyline HCl and theophylline were employed as the high and low solubility model drugs, respectively. The incorporation of different excipient concentrations and changes in formulation components influenced the drug release dynamics as evidenced by computed mathematical quantities (t x%, MDT x%, f 1, f 2, k 1, k 2, and К F). The effects of excipients on drug release from the PA 6,10 monolithic matrix was further elucidated using static lattice atomistic simulations wherein the component energy refinements corroborates the in vitro and in silico experimental data. Consequently, the feasibility of modulating release kinetics of drug molecules from the novel PA 6,10 monolithic matrix was well suggested. 相似文献
19.
20.
Wexler DS Gao L Anderson F Ow A Nadasdi L McAlorum A Urfer R Huang SG 《Journal of biomolecular screening》2005,10(4):383-390
Solubility and permeability are intimately linked in drug absorption processes. They have, however, been traditionally assayed separately. To support this linkage, a combined solubility/permeability assay was developed for determining absorption properties of chemical entities. First, solubility is determined at 4 pH values by comparing the concentration of a saturated compound solution to its dilute, known concentration. The filtered, saturated solution from the solubility assay is then used as input material for the membrane permeability determination. The permeability assay is a parallel artificial membrane technique whereby a membrane is created on a solid support parallel artificial membrane permeation assay (PAMPA). The 2 artificial membranes presented here model the gastrointestinal tract and the blood-brain barrier (BBB). Data are presented for control compounds, which are well documented in the literature and exemplify a range of solubility and membrane permeability. The advantages of the combination method are 1) reduction of sample usage and preparation time, 2) elimination of interference from compound precipitation in membrane permeability determination, 3) maximization of input concentration to permeability assay for improved reproducibility, and 4) optimization of sample tracking by streamlining data entry and calculations. BBB permeability ranking of compounds correlates well with literature CNS activity. 相似文献