Biomedical subjects

Ramesh Panchagnula

Publications and source records attributed to Ramesh Panchagnula.

At least 55 records · Page 3Linked to original sources

PubMed2004

RP-HPLC method and its validation for the determination of naloxone from a novel transdermal formulation.

The aim of the present work was to develop a simple and reliable liquid chromatographic method for the quantitative determination of naloxone (NLX) in a novel transdermal formulation. Chromatography was carried out by reversed-phase technique on a C-18 column with a mobile phase composed of methanol, acetonitrile and 50 mM phosphate buffer (pH 7) in the proportion of 40:20:40 v/v/v, at a flow rate of 1 ml/min. The UV spectrophotometric determination was performed at 220 nm. This method was found to be specific and accurate with the mean recovery of 98.72% in the range of 2-50 microg/ml, and a run time of 15 min (retention time of NLX 11.3 min). Method was applied for stability testing of novel transdermal formulation developed in our laboratory. Assay content of NLX in the formulation was determined in stability samples and compared with the control samples. Statistical analysis by Student's t-test showed no significant difference between the assay content of NLX in control and test samples at 95% confidence interval. Overall, the proposed method is highly sensitive, precise and accurate and can be used for the reliable quantitation of NLX in developed transdermal formulation with the added advantage of simple procedure.

Administration, Cutaneous↗

PubMed2004

Bioequivalence trials of rifampicin containing formulations: extrinsic and intrinsic factors in the absorption of rifampicin.

Rifampicin shows variable bioavailability from solid oral dosage forms and the reasons for this variable absorption reported in literature varies from extrinsic formulations factors to intrinsic variability in rifampicin absorption. Hence, we have undertaken a systematic and comprehensive evaluation of all the factors to study contribution of all the factors on rifampicin absorption. As a first step, data from eight bioequivalence studies conducted at National Institute of Pharmaceutical Education and Research (NIPER) bioavailability center was compared across the trials to understand the effect of extrinsic/intrinsic factors on the bioavailability of rifampicin, isoniazid and pyrazinamide. Out of eight fixed dose combination (FDC) formulations, six formulations were bioequivalent for rifampicin to separate formulations whereas one formulation was below and one was above the limits of bioequivalence. It was observed that more variability in rifampicin blood levels is associated with FDC formulations when compared to rifampicin-only formulations and was attributed to complexity involved in the manufacturing of FDCs. Further, one of the rifampicin-only capsule showed unexpectedly lower plasma levels indicating role of physical characteristics of rifampicin bulk material. It was also seen that rifampicin shows dose-dependent pharmacokinetics even at the modest increase in dose due to saturation of efflux system at absorption site and metabolizing enzymes for elimination. Other components of FDC formulations such as isoniazid and pyrazinamide due to high solubility and permeability have shown very less variability and were bioequivalent to separate formulations even from formulations those were failed for rifampicin. The comparison of data across the trials suggested that rifampicin bioavailability problem is more attributable to the extrinsic factors such as formulation or rifampicin bulk material rather than intrinsic variability of rifampicin absorption.

Adolescent↗

PubMed2004

Biopharmaceutic classification system: a scientific framework for pharmacokinetic optimization in drug research.

The tenets of biopharmaceutics, solubility and permeability, are of pivotal importance in new drug discovery and lead optimization due to the dependence of drug absorption and pharmacokinetics on these two properties. A classification system for drugs based on these two fundamental parameters, Biopharmaceutic Classification System (BCS), provides drug designer an opportunity to manipulate structure or physicochemical properties of lead candidates so as to achieve better "deliverability". Considering the facts for failure of NCEs, drug research, once concentrating on optimizing the efficacy and safety of the leads, dramatically transformed in the past two decades. With the enormous number of molecules being synthesized using combinatorial and parallel synthesis, high throughput methodologies for screening solubility and permeability has gained significant interest in pharmaceutical industry. Ultimate aim of the drug discovery scientist in pharmacokinetic optimization is to tailor the molecules so that they show the features of BCS class I without compromising on pharmacodynamics. Considerations to optimize drug delivery and pharmacokinetics right from the initial stages of drug design propelled need for "High Throughput Pharmaceutics" (HTP). In silico predictions and development of theoretical profiles for solubility and lipophilicity provides structure based biopharmaceutical optimization, while in vitro experimental models (microtitre plate assays and cell cultures) validate the predictions. Thus, biopharmaceutical characterization during drug design and early development helps in early withdrawal of molecules with insurmountable developmental problems associated with pharmacokinetic optimization.

Animals↗

PubMed2003

Design of controlled release delivery systems using a modified pharmacokinetic approach: a case study for drugs having a short elimination half-life and a narrow therapeutic index.

The objectives of peroral controlled release drug delivery systems (CRDDS) are to maintain therapeutically effective plasma drug concentration levels for a longer duration thereby reducing the dosing frequency and to minimise the plasma drug concentration fluctuations at steady state by delivering drug in a controlled and a reproducible manner. Drug delivery rate, duration of delivery and the dosing interval are the target features for any temporal CRDDS. The classical pharmacokinetic model for designing CRDDS [Drug Dev. Ind. Pharm. 15 (1989) 1073] assumes the time of drug delivery (t(del)) to be less than the dosing interval. However, termination of drug release from such a CRDDS at t(del) and/or a declining drug input function towards the terminal phase of t(del) from a first order kinetic CRDDS can have severe implications on plasma drug concentration and steady state fluctuations for a drug with very short half-life. A case study is presented in this paper, wherein by means of theoretical calculations using a classical pharmacokinetic approach, it is shown that a first order kinetic CRDDS for hypothetical drugs with short elimination half-life and different pharmacokinetic conditions would result in sub-therapeutic plasma concentrations at least for some time during the dosing interval at steady state. In order to avoid sub-therapeutic plasma drug concentrations a modification in classical pharmacokinetic model is proposed and discussed through theoretical calculations for different hypothetical pharmacokinetic situations and a practical single dose pharmacokinetic study with a first order kinetic CRDDS for nifedipine (a short half-life drug; about 2h). It is shown that improved therapeutic efficacy could be expected from a CRDDS developed based on proposed modification in the classical pharmacokinetic model.

Administration, Oral↗

PubMed2003

Transdermal delivery of insulin from poloxamer gel: ex vivo and in vivo skin permeation studies in rat using iontophoresis and chemical enhancers.

Gels are considered to be the most suitable delivery vehicle for iontophoresis, as they can be easily amalgamated with the iontophoretic delivery system and can also match the contours of the skin. Insulin was used as a model peptide for large peptides in the molecular weight range of 3-7 kDa. A gel formulation of insulin was formulated using poloxamer 407 and was evaluated by ex vivo and in vivo skin permeation studies in rat with chemical enhancer and/or iontophoresis. The poloxamer gel was physically and chemically stable during the storage period. In ex vivo studies, both linoleic acid and menthone in combination with iontophoresis showed a synergistic enhancement of insulin permeation. The plasma insulin concentration (PIC) was highest with linoleic acid pre-treatment, in agreement with ex vivo permeation studies, but the reduction in plasma glucose levels (PGL) was comparable to iontophoresis. Menthone pre-treatment resulted in rapid attainment of peak PIC, but the reduction in PGL was less than other treatment groups. There was no direct relation between PIC and PGL and is attributed to the fact that the action of insulin in mediated by a cascade of cellular mechanisms, before a reduction in PGL is observed. However, iontophoresis either alone or in combination with linoleic acid produced a reduction in PGL to the extent of 36-40%. A combination of chemical enhancers and iontophoresis caused greater skin irritation than when either of them was used alone.

Administration, Cutaneous↗

PubMed2003

Transdermal iontophoresis of insulin. II. Physicochemical considerations.

Transdermal iontophoresis is one of the potential enhancement strategies for the delivery of large and charged molecules. Insulin, a polypeptide of 6 kDa was used as a model for large peptides to understand the influence of peptide concentration, NaCl concentration, buffer type and its concentration on the transport efficiency of iontophoresis. Maximum enhancement was found at 3 mg/ml (75 IU/ml). The permeation of insulin was found to increase up to 0.05 M NaCl and decreased at higher concentrations of NaCl. The glucose permeation studies showed that permeation of insulin increased in the presence of NaCl due to ion induced convective flow. The flux enhancement of insulin in the presence of phthalate buffer was higher in comparison to citrate buffer, but the enhancement in these two buffers was the same in the presence of 0.05 M NaCl, which was also supported by a similar trend in conductivity values. However, the solution conductivity values did not reflect the influence of co-ions and counter ions on the transport of large peptides across the skin. Overall the findings revealed that the transport efficiency of large peptides like insulin may be improved by the optimisation of competing ions in solution.

Administration, Cutaneous↗

PubMed2003

Transdermal iontophoresis of insulin. V. Effect of terpenes.

To increase the skin permeation of large peptides like insulin, it is necessary to utilize a combination of enhancement strategies. In this regard, this study investigated the effect of terpenes/EtOH combination in comparison to EtOH and neat terpene on transdermal iontophoretic permeation of insulin. Ex-vivo experiments were conducted using full thickness rat skin after pre-treatment for 2 h with 5% of menthol, menthone, cineole and pulegone in EtOH; EtOH alone; neat menthone with and without iontophoresis (0.5 mA/cm(2); 6 h). FT-IR studies were carried out using rat epidermal sheets after pre-treatment with enhancer solution for 2 h and tritiated water permeation studies was used to investigate the alteration in skin barrier property after enhancer or current treatment. The lag time was significantly reduced (P<0.05) with terpene/EtOH pre-treatment in comparison to passive control and EtOH pre-treatment, although there was no significant difference (P>0.05) among the terpenes. Synergistic enhancement in flux was observed with terpene/EtOH, and menthone/EtOH showed highest enhancement among the terpene/EtOH combinations. On the other hand, enhancement with neat menthone was higher than with menthone/EtOH. FT-IR studies showed that terpene/EtOH, EtOH and neat terpene act at the intercellular lipids. The skin barrier property was significantly (P<0.05) compromised with neat menthone treatment. Iontophoresis had a lesser effect on skin barrier property compared to chemical enhancer pre-treatment. Terpene/EtOH caused synergistic enhancement of insulin permeation when combined with iontophoresis and was influenced by the type and concentration of terpene.

Administration, Cutaneous↗

PubMed2003

Effect of temperature on imipramine hydrochloride permeation: role of lipid bilayer arrangement and chemical composition of rat skin.

The aim of this investigation was to study the effect of temperature on the permeation of imipramine hydrochloride (IMH) across rat skin from two different vehicles. Differential scanning calorimetry (DSC) was used to characterize the phase transitions of rat epidermis and extracted rat SC lipids, and the transition temperatures were correlated with the permeability of IMH at different temperatures. Permeability of IMH from ethanol and propylene glycol (PG) was determined at five different temperatures and observed that a significant increase in IMH permeability occurred 45 degrees C from both the vehicles. Further, high energies of activation for rat skin permeation suggested that IMH diffuses across intercellular lipid matrix and therefore any change in the packing of SC lipids will have an effect on IMH permeation. Three endotherms T(1), T(2) and T(3) of rat epidermis were observed in DSC thermograms at 44, 53 and 64 degrees C and were assigned as transitions corresponding to orthorhombic to hexagonal, hexagonal to more disordered phase and melting of lipids with high cholesterol content, respectively. The high permeability values of IMH above 45 degrees C were therefore reasoned to be because of orthorhombic to hexagonal phase transition in rat skin from close to that temperature.

Animals↗

PubMed2003

In vitro evaluation of food effect on the bioavailability of rifampicin from antituberculosis fixed dose combination formulations.

Rifampicin is one of the major first line anti-tuberculosis drugs used in the therapy of tuberculosis. In literature, there are conflicting reports regarding effect of food on the bioavailability of rifampicin. In vitro, effect of food on the bioavailability can be studied by simulating in vivo conditions in dissolution fluid hence, to understand the variable effect of food on rifampicin release, dissolution studies were done by simulating in vivo conditions after meal intake. In this study, we assessed the effect of hydrodynamic stress in presence of food and meal composition on two rifampicin containing fixed dose combination formulations by carrying out dissolution at different agitation rates (simulation of fasted and fed state) as well as in the presence of different percentage of oil (fatty food). Agitation intensity as well as presence of oil did not had any influence on rifampicin release from formulation A. This formulation had shown excellent release characteristics at all the conditions studied. Whereas, formulation B showed agitation rate dependent release and also release was affected in presence of oil. Hence, it is concluded that food may not have any effect on the release of rifampicin from the formulation and subsequently on its bioavailability if the formulation has excellent release profile (>85% release in 10 min). Further, effect of food on the rifampicin release was a function of dosage form characteristics such as disintegration time and dissolution rate, which will subsequently affect the release behavior of a formulation in presence of food.

Antitubercular Agents↗

PubMed2003

Transdermal delivery of zidovudine: effect of vehicles on permeation across rat skin and their mechanism of action.

The purpose of this study was to investigate the effects of various solvent systems containing water, ethanol, propylene glycol (PG), and their binary combinations on the ex vivo permeation of zidovudine (AZT) across Sprague-Dawley rat skin using Franz diffusion cells at 37 degrees C. Further, saturation solubility and epidermis/vehicle partition coefficient of AZT in the solvent systems, and their effect on percentage hydration of epidermis using thermogravimetric analysis were determined to understand the mechanisms by which these solvent systems change drug permeability properties. All binary combinations of PG, ethanol and water significantly increased saturation solubility of AZT. Maximum AZT flux was observed with 66.6% ethanol among ethanol-water solvents, with 33.3% PG in PG-water solvents and with 100% ethanol among PG-ethanol combinations. PG-water and PG-ethanol solvents neither reduced the lag time nor increased AZT flux across rat skin. In addition, high concentrations of PG in both water and ethanol reduced steady state flux of AZT. Further, thermogravimetric studies revealed that solvents containing high PG concentrations dehydrate epidermis. Among all the solvent combinations, highest flux and short lag time were achieved with ethanol at 66.6% in water and hence is a suitable vehicle for transdermal delivery of AZT.

Administration, Cutaneous↗

PubMed2003

Effect of iontophoresis and fatty acids on permeation of arginine vasopressin through rat skin.

The aim of this study was to assess the effects of fatty acids and iontophoretic mode of penetration enhancement on transdermal delivery of Arginine Vasopressin (AVP). Sprague-Dawley (SD) rat skin was pretreated with fatty acids (e.g. 5% w/v, lauric acid, oleic acid, and linoleic acid in ethanol:water (EtOH:W, 2:1 system) for 2h and iontophoresis in vitro, separately or together. The results indicate that all fatty acids studied increased (P<0.05) the flux of AVP in comparison to control (not pretreated with enhancer) and their effectiveness in flux enhancement was comparable. Further, oleic acid in combination with iontophoresis significantly increased the permeation of AVP both in comparison to pretreatment with fatty acids and iontophoresis alone. However, iontophoresis did not further increase the permeation of AVP through linoleic acid pretreated skin. Fourier transform infrared (FT-IR) spectroscopic studies revealed that EtOH:W (2:1) system is not effective in lipid extraction. The shift to higher wavenumbers of the symmetric and asymmetric stretching peaks at 2850 and 2920cm(-1) revealed that at the concentration used, oleic acid and linoleic acid caused fluidization of stratum corneum (SC) lipids. This study provides direct evidence that oleic acid in EtOH:W (2:1) system causes disruption of the SC lipid lamellae and that a combination of oleic acid with iontophoresis further enhances the effects of oleic acid in a synergistic manner.

Administration, Cutaneous↗

PubMed2003

Poloxamer gel as vehicle for transdermal iontophoretic delivery of arginine vasopressin: evaluation of in vivo performance in rats.

The present study describes the formulation and evaluation for pharmacokinetic and pharmacodynamic activity of arginine vasopressin (AVP), a nanopeptide with antidiuretic activity on being delivered by transdermal iontophoresis. Poloxamer 407 was used to form stable gels that did not reduce the release of AVP. The release rate from the gel followed Higuchi kinetics indicating that the dominant mechanism of release is diffusion. Iontophoresis alone and in combination with chemical enhancers was used to augment the transdermal permeation of AVP. The results of both pharmacokinetic and pharmacodynamic studies emphasize the dimension of 'rapid onset' achieved by iontophoresis. The correlation between pharmacokinetic data and pharmacodynamic activity was only qualitative. Histopathological studies revealed that skin toxicity caused by either iontophoresis or chemical enhancers when used alone could be reduced by using a combination of both the techniques in tandem.

Administration, Cutaneous↗

PubMed2003

Physicochemical considerations in the iontophoretic delivery of a small peptide: in vitro studies using arginine vasopressin as a model peptide.

Transdermal iontophoresis (TI) is a physical enhancement technique to facilitate the delivery of primarily charged molecules across the skin. TI of peptides is influenced by a complex interplay of several factors and one of the main issues in optimizing iontophoretic delivery of peptides is to improve the transport efficiency. From this perspective, this study investigates the effect of the physicochemical parameters on the TI of a peptide arginine vasopressin (AVP). The permeation of AVP showed a linear dependence on the concentration of drug in the donor medium. The iontophoretic flux of AVP was strongly influenced by the pH of the donor solution. Increasing the pH from 5.16 to 7.4 resulted in a decrease in the enhancement ratio by 4.5 times. When the ionic strength was increased by varying the amount of NaCl from 0.05 to 0.25 M the flux was found to decrease by 3.2 times. Replacing normal saline in the receptor compartment by HEPES buffer showed a resultant four times increase in drug permeation. The physiochemical parameters of the donor medium play a significant role in the efficiency of drug delivery by iontophoresis for a small peptide like AVP. Though electrorepulsion would be expected to be the main mechanism involved in the movement of charged molecules across the skin by iontophoresis, for peptides in the molecular weight range of AVP, other associated secondary effects like osmosis, electroosmosis and counter ion flow may also play a significant role in transport across the skin.

Administration, Cutaneous↗

PubMed2003

P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement.

Drug efflux pumps like P-glycoprotein (P-gp) and multidrug resistance (MDR) proteins were recognized to possess functional role in determining the pharmacokinetics of drugs administered by peroral as well as parenteral route. Advancements in molecular biology, to some extent, had revealed the structure, localization and functional role of P-glycoprotein and its mechanism of drug efflux. Broad substrate recognition by this protein and clinical implications of its inhibition has revolutionized cancer chemotherapy leading to design and development of novel P-glycoprotein inhibitors. In the recent times, the application of these inhibitors in improving peroral drug delivery has gained special interest. Inhibition of P-glycoprotein improves intestinal absorption and tissue distribution while reducing the substrate metabolism and its elimination. Eventually, various screening methodologies have been developed for determining the activity of P-glycoprotein, kinetics of drug transport and identification of substrates and inhibitors. In the present review, techniques used for screening P-glycoprotein inhibitors and the scope of these inhibitors in optimizing peroral drug absorption and pharmacokinetics are discussed along with a brief introduction to P-glycoprotein, its physiological function and active role in extrusion of drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Evaluation of bioequivalence of isoniazid and pyrazinamide in three and four drugs fixed dose combinations using WHO simplified protocol.

The reliable supply of quality drugs in the form of fixed dose combination (FDC) is an essential part of tuberculosis treatment. The objective of this investigation was to evaluate whether the World Health Organization (WHO) simplified screening protocol for the bioequivalence assessment of rifampicin can be used for the evaluation of other components of FDC so as to ensure the bioavailability of all drugs at tissue site. These bioequivalence studies were conducted on 20 and 22 healthy male volunteers for evaluation of three and four drugs FDC formulations, respectively. Both studies were conducted as randomized, open, crossover trials and sampling schedule was upto 8h according to WHO recommended protocol for evaluation of rifampicin bioequivalence. The bioequivalence of isoniazid and pyrazinamide were estimated using AUC(0-8), AUC(0-alpha), and C(max). FDC formulation was considered bioequivalent to separate formulations for isoniazid and pyrazinamide if bioequivalence limit fall in between 0.80 and 1.25. Bioequivalence estimates of AUC(0-8) and AUC(0-alpha) for isoniazid and all the three pharmacokinetic measures of pyrazinamide were within the acceptable limits, whereas C(max) of isoniazid from four drugs FDC was outside the limit when evaluated by two-way ANOVA. After evaluation of isoniazid and pyrazinamide based on their pharmacokinetics, it was found that C(max) is being affected by limited sampling time points of WHO protocol. Further, AUC was a robust parameter unaffected by sampling schedule adopted. The WHO simplified protocol for assessment of rifampicin is also suitable for evaluating bioequivalence of isoniazid and pyrazinamide from FDC formulations. However, for comparison of rate of absorption by means of C(max), careful evaluation of concentration-time profile along with pharmacokinetics is necessary before final judgment.

Administration, Oral↗

PubMed2003

Plasma pooling methodology as a faster and cheaper tool to evaluate bioequivalence of rifampicin component of FDCs of antitubercular drugs.

Rifampicin is one of the most important first line drugs used in fixed dose combinations (FDCs) of antitubercular drugs. The chances of reduced bioavailability of rifampicin from FDCs necessitated its evaluation against standard formulations of individual drugs in bioequivalence studies. This study was undertaken to evaluate the importance of plasma pooling methodology as a rapid and cheaper tool to evaluate bioequivalence of rifampicin component of FDCs of antitubercular drugs. Plasma samples of volunteers obtained from bioequivalence studies were pooled according to volunteer and time-wise pooling. Area under the plasma concentration versus time curves (AUCs) of rifampicin was reduced in the pooled plasma samples when compared to the individual samples. However, the ratio of AUCs of FDCs to that of separate formulations was found to be comparable for both the individual samples and pooled samples data. Concentration-time profiles of rifampicin obtained after time-wise pooling were subjected to non-compartmental analysis for determination of pharmacokinetic parameters. Whereas bioequivalence estimates were determined using individual AUC values obtained from volunteer-wise pooling. Results indicated the possibility of using plasma pooling methodology in bioequivalence estimation of rifampicin to simplify and accelerate the registration process.

Adolescent↗

PubMed2003

Transdermal iontophoresis of insulin. Part 1: A study on the issues associated with the use of platinum electrodes on rat skin.

We have studied the issues associated with the use of platinum electrodes for transdermal iontophoretic delivery of peptides, using insulin as a model peptide. Insulin permeation was studied using full-thickness rat skin by varying the donor solution pH as a function of electrode polarity. The stability of insulin under the iontophoretic conditions was studied using TLC, SDS-polyacrylamide gel electrophoresis and HPLC. Large pH shifts were observed during anodal iontophoresis (AI), when the donor solution pH was above the isoelectric point of insulin and in cathodal iontophoresis (CI), when the donor solution pH was below the isoelectric point of insulin. The direction and magnitude of electroosmotic flow was influenced by pH of the donor solution and the electrode polarity. On the other hand, the buffer used to maintain the pH governed the contribution of electrorepulsion to the overall transport of insulin. Electrochemical degradation of insulin was significant during AI at pH 7.4. Among the pH investigated, AI of insulin at pH 3.6 and CI at pH 8.35 were better, as the pH shift was relatively less and electrochemically more stable during iontophoresis as compared with other pH. In summary, the pH shift caused by platinum electrodes had a significant influence on the permeation and stability of insulin.

Animals↗

PubMed2002

Analytical method for monitoring concentrations of cyclosporin and lovastatin in vitro in an everted rat intestinal sac absorption model.

Cyclosporin A (CSA) and lovastatin (LV) are lipophilic drugs, which show poor and erratic absorption when administered perorally. The permeability of these compounds can be increased transiently by altering the membrane characteristics of the absorptive epithelium by the use of sorption promoters (SPs). In the present work a simple validated HPLC method utilizing an isocratic mobile phase with short retention times for CSA and LV was developed in order to monitor their concentrations in Kreb's Ringer bicarbonate (KRB) solution in vitro in intestinal sac absorption model. The same method was utilized to determine the apparent permeability coefficients and absorption profiles of CSA and LV by a modified Wilson-Wiseman method. Drugs were analysed by a reversed-phase HPLC method using a Shim-pack C18 column. An isocratic mobile phase containing acetonitrile and water in the proportions 70:30 and 80:20 was used for the HPLC analysis of CSA and LV, respectively. The flow-rate was 2 ml/min and quantitative determinations were carried out at 215 nm at 70 degrees C for CSA. In the case of LV the flow-rate was 1 ml/min and detection was done at 238 nm at 25 degrees C. The method was found to be specific as none of the proposed SPs, components of KRB or intestinal sac artefacts interfered with the drug peaks. Recovery studies and intra- and inter-day variations were within statistical limits. The limits of detection were 250 and 10 ng/ml and the limits of quantitation were 400 and 30 ng/ml for CSA and LV, respectively. The calibration curve was found to be linear in concentration range of 0.5-6 microg/ml for CSA and 0.05-0.4 microg/ml for LV. The proposed method was found to be rapid and selective and hence can be applied for continuous monitoring of CSA and LV in vitro in intestinal sac absorption studies.

Animals↗