ABSTRACT
OBJECTIVE: There is no standard mechanism for empathy guidance and counselling for medical students. This study aimed to determine the dimensionality and reliability of a questionnaire developed for establishing guidance and counselling for pre-clinical medical students at Universiti Sains Malaysia (USM). METHODS: A cross-sectional study was conducted among undergraduate medical students of the School of Medical Sciences of USM. The proposed USM Medical Students' Guidance and Counselling Needs (USM-MSGCN) questionnaire is a self-administered instrument that consists of 68 initial items developed from the recommendation of medical students, counsellors, and lecturers in the medical education department. To determine the dimensionality (construct validity) and reliability of the questionnaire, exploratory factor analysis and Cronbach's alpha internal consistency reliability analysis were conducted. RESULTS: A total of 208 students participated in the study. Factor analysis revealed that the items were not unidimensional; four potential constructs could be extracted from the questionnaire, namely, self-leadership (7 items), communication (5 items), learning (5 items), and psychological coping skills (3 items), with factor loading ranges of 0.56-0.82, 0.56-0.88, 0.65-0.84, and 0.79-0.80, respectively. These domains had the following internal consistency reliability (Cronbach's alpha): 0.89, 0.90, 0.87, and 0.87, respectively; the overall alpha value was 0.93. CONCLUSION: Four factors, with 20 items in the USM-MSGCN questionnaire had good validity and reliability values when administered among the pre-clinical medical students.
ABSTRACT
A rapid, sensitive and selective liquid chromatography-mass spectrometry (LC-MS) assay has been developed for determination of cyclosporin A (CyA) in human plasma; cyclosporin B (CyB) was used as internal standard (IS). The method utilized a combination of a column-switching valve and a reversed-phase symmetry column. The mobile phase was a 25:75 (v/v) mixture of 10% aqueous glacial acetic acid and acetonitrile. Running time per single run was less than 10 min. Sample preparation included C8 SPE of human plasma spiked with the analyte and internal standard, evaporation of the eluate to dryness at 50 degrees C under N2 gas, and finally reconstitution in the mobile phase. Detection of cyclosporin A and the IS was performed in selected ion-monitoring mode at m/z 601.3 and 594.4 Da for CyA and IS, respectively. Quantitation was achieved by use of the regression equation of relative peak area of cyclosporin to IS against concentration of cyclosporin. The method was validated according to FDA guideline requirements. The linearity of the assay in the range 5.0-400.0 ng mL(-1) was verified as characterized by the least-squares regression line Y = (0.00268+/-1.9 x 10(-4))X+(0.00078+/-1.8 x 10(-3)), correlation coefficient, r = 0.9986+/-1.1 x 10(-3) (n = 48). Intra and inter-day quality-control measurements in the range 5.0-350.0 ng mL(-1) revealed almost 100% accuracy and < or = 9% CV for precision. The mean absolute recovery of CyA was found to be 84.01+/-9.9% and the respective relative recovery was 100.3+/-9.19. The limit of quantitation (LOQ) achieved was 5 ng mL(-1). Eventually, stability testing of the analyte and IS in plasma or stock solution revealed that both chemicals were very stable when stored for long or short periods of time at room temperature or -20 degrees C.
Subject(s)
Chromatography, Liquid/methods , Cyclosporine/blood , Spectrometry, Mass, Electrospray Ionization/methods , Humans , Quality Control , Reference Standards , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
A validated liquid chromatographic-mass spectrometric (LC/MS) method for the determination of lisinopril in human plasma is presented. Enalapril was used as an internal standard. After the addition of internal standard, solid phase extraction was used as a cleaning step. To separate lisinopril and enalapril from interfering endogenous plasma substances, the analysis was performed using column switching valve. The quantitative determination was performed using selected ion monitoring (+)-electrospray LC-MS. A combination of an acidic mobile phase and a reverse phase column was used. A precision in the linear range from 10 to 500.0 ng/mL plasma, absolute recovery of 91.69% for lisinopril and 90.26% for enalapril, stability for 3.5 months at -20 degrees C have been achieved. Limit of quantitation (LOQ) was 10 ng/mL while limit of detection (LOD) was about 1 ng/mL.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/blood , Lisinopril/blood , Calibration , Chromatography, High Pressure Liquid , Enalapril/blood , Freezing , Humans , Mass Spectrometry , Quality Control , Reference Standards , Reproducibility of ResultsABSTRACT
Two studies have been performed to assess the relative bioavailability of Azomycin (Julphar, UAE) as compared with Zithromax (Pfizer, USA) at the International Pharmaceutical Research Center (IPRC), Amman, Jordan. One study involved Azomycin capsules and the other Azomycin suspension. Each study enrolled 24 volunteers and in both studies, after an overnight fasting, the two brands of azithromycin were administered as single dose on two treatment days separated by a 2 weeks washout period. After dosing, serial blood samples were collected for a period of 192 h. Plasma harvested from blood, was analysed for azithromycin by HPLC coupled with electrochemical detection. Various pharmacokinetic parameters including AUC(0-t,) AUC(0-infinity,) C(max), T(max), T(1/2) and K(elm) were determined from plasma concentrations for both formulations and found to be in good agreement with the reported values. AUC(0-t), AUC(0-infinity) and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence intervals for the test/reference ratios of these parameters were found within the bioequivalence acceptance range of 80-125%. Based on these statistical inferences it was concluded that Azomycin capsule is bioequivalent to Zithromax capsule and Azomycin suspension is bioequivalent to Zithromax suspension.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Azithromycin/blood , Azithromycin/pharmacokinetics , Nitroimidazoles/pharmacokinetics , Administration, Oral , Adolescent , Adult , Analysis of Variance , Anti-Bacterial Agents/blood , Area Under Curve , Chemistry, Pharmaceutical , Confidence Intervals , Humans , Male , Therapeutic EquivalencyABSTRACT
Release of salicylic acid, diclofenac acid, diclofenac diethylamine and diclofenac sodium, from lyotropic structured systems, namely; neat and middle liquid crystalline phases, across mid-dorsal hairless rat skin into aqueous buffer were studied. Release results were compared with those from the isotropic systems. The donor systems composed of the surfactant polyoxyethylene (20) isohexadecyl ether, HCl buffer of pH 1 or distilled water and the specific drug. High performance liquid chromatography (HPLC) methods were used to monitor the transfer of the drugs across the skin barrier. Results indicated that the rate-determining step in the transport process was the release of the drug from the specified donor system. Further, apparent zero order release was demonstrated with all systems. Except for diclofenac sodium, drug fluxes decreased as the donor medium changed from isotropic to anisotropic. The decrease in fluxes was probably due to the added constrains on the movement of drug molecules. By changing the anisotropic donor medium from neat to middle phase, drug flux decreased in case of salicylic acid and diclofenac sodium. In the mean time, flux increased in case of the diethylamine salt and appeared nearly similar in case of diclofenac acid. Rates of drug transfer across the skin from the anisotropic donors seemed to be largely controlled by the entropy contribution to the transport process. The type and extent of drug-liquid crystal interactions probably influenced the latter.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Diclofenac/pharmacokinetics , Salicylic Acid/pharmacokinetics , Skin/metabolism , Surface-Active Agents/administration & dosage , Animals , Diclofenac/administration & dosage , Male , Rats , Rats, Sprague-Dawley , Salicylic Acid/administration & dosageABSTRACT
The experimental work of studying the adsorption of ketotifen and allopurinol by chitosan focused on determining the solubilities and the adsorption isotherms of the adsorbates employed in this study. The adsorption of the aforementioned compounds by chitosan was studied using the rotating bottle method. The concentrations, both before and after the attainment of equilibrium, were determined with the aid of a reversed-phase high-performance liquid chromatography column. The results of these studies demonstrated that ketotifen and allopurinol are both adsorbed by chitosan. The nonlinear Langmuir-like and the Freundlich models both were applied to the experimental data. The correlation coefficients obtained from the nonlinear Langmuir-like model were better than those obtained from Freundlich model, suggesting that allopurinol and ketotifen interacted with certain specific binding sites on the chitosan surface. The allopurinol adsorption experiments indicated that the particle size of chitosan and therefore the surface area can significantly affect the Langmuir capacity constant, while the affinity constants are statistically the same. As expected from the solubility studies, the ketotifen adsorption experiments at 2 different pHs (7 and 10) showed that the adsorption affinity at pH 10 was much higher than at pH 7. What was not expected was that the capacity constants were significantly different, suggesting that further studies are needed using common ion buffers and multicomponent adsorption for the proper mechanism to be determined.
Subject(s)
Allopurinol/pharmacokinetics , Chitin/analogs & derivatives , Chitin/chemistry , Ketotifen/pharmacokinetics , Adsorption , Allopurinol/chemistry , Chitosan , Ketotifen/chemistry , Particle Size , SolubilityABSTRACT
The purpose of this study was to investigate oral absorption of two metronidazole suspension products, Flagyl((R)) and a test product. Twenty-four healthy volunteers participated in the study. The crossover study was done in a two-phase, two-sequence manner with a 2-week washout period. Individual disposition kinetics were determined by non-compartmental analysis. AUC(0-infinity) and C(max) values were 1.26 and 1.86 times more in the case of test formulation. Mean plasma drug concentrations were analyzed to estimate the rate and extent of oral absorption. The optimized duodenal, jejunal1, jejunal2, illial1, ileal2, ilial3, ilial4, colonic permeability values (x10(-4)) for the test and Flagyl products were 3.96, 3.96, 3. 96, 0.68, 0.37, 0.01, 0.12, 0.38 and 2.34, 0, 0, 1.2, 1.1, 0.9, 0.3, 0.04cm/s, respectively. The total fraction of oral dose absorbed for the test and Flagyl products were 95.5% and 65.6% respectively, consistent with the pharmacokinetic ratios. The test product exhibited significantly higher absorption rate and extent than Flagyl, but both show similar half-lives. Sensitivity analysis showed that drug absorption is sensitive to effective permeability but not sensitive to particle radius and small intestinal transit time. The two products were found bio-inequivalent which is suggested to be due to differences in formulation additives that decreased the effective permeability of Flagyl.
Subject(s)
Anti-Infective Agents/pharmacokinetics , Metronidazole/pharmacokinetics , Absorption , Administration, Oral , Area Under Curve , Humans , Male , SuspensionsABSTRACT
BACKGROUND: Although cystic fibrosis is the most common genetic disorder of children, its heterogeneous spectrum of severity lends itself to underdiagnosis in the older adult patient population where the index of suspicion is not high. METHODS: We report a 60-year-old Hispanic man with asthma who presented with progressive dyspnea and wheezing unresponsive to inhaled corticosteroid treatment. Additionally, he had clinical findings and a past history suggestive of cystic fibrosis. Skin testing, radiography and laboratory studies were completed to evaluate for allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis. RESULTS: Test results revealed peripheral eosinophilia and hyper IgE. Skin testing to Aspergillus fumigatus (Af) was positive. IgG, IgM, and Af specific antibodies were present. High resolution CT scan showed central bronchiectasis. Sweat tests were positive on two separate occasions and gene analysis showed our patient to have a positive gene mutation at D127ON/D127ON. CONCLUSION: Cystic fibrosis should be suspected in the older adult patient with a compatible clinical presentation.
Subject(s)
Aspergillosis, Allergic Bronchopulmonary/diagnosis , Cystic Fibrosis/diagnosis , Aspergillosis, Allergic Bronchopulmonary/complications , Asthma/complications , Diagnosis, Differential , Family Health , Humans , Male , Middle Aged , Respiratory Function Tests , Sputum/microbiologyABSTRACT
Sustained-release polymer beads containing diclofenac sodium (DNa) dispersed in Compritol 888 and encapsulated in calcium alginate shell were prepared utilizing 2(3) factorial design. The effect of sodium alginate concentration, drug: Compritol 888 weight ratio and CaCl2 concentration on drug content (%), time for 50% and 80% of the drug to be released, and mean dissolution time (MDT) were evaluated with analysis of variance (ANOVA). An increase in the level of all these factors caused retardation in the release, and t50%, t80%, and MDT were increased. The drug release was dependent on the pH of the release media. A formula that gives a release comparable to commercial products was prepared.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Chemistry, Pharmaceutical/methods , Diclofenac/administration & dosage , Alginates , Analysis of Variance , Drug Carriers , Drug Compounding , Excipients , Fatty Acids , Glucuronic Acid , Hexuronic AcidsABSTRACT
The development and evaluation of HPLC method for quantifying cetirizine in human serum is described. The method involves liquid phase extraction of cetirizine in methylene chloride, adding diazepam as an internal standard, followed by separation on a reversed phase C18 Novapak column (150 x 3.9 nm; 4 microm), and employing a UV-detection set at 230 nm at ambient temperature. The mobile phase consists of a 13 mM phosphoric acid solution and acetonitrile (61:39 v/v) adjusted to pH 2.8 with 5 M NaOH. The assay is linear from 10 to 500 ng ml(-1) with a detection limit of 5 ng ml(-1) and a mean recovery of 96.5%. The applicability of this method in pharmacokinetic studies is evaluated.
Subject(s)
Cetirizine/blood , Chromatography, High Pressure Liquid/methods , Histamine H1 Antagonists/blood , Cetirizine/pharmacokinetics , Histamine H1 Antagonists/pharmacokinetics , Humans , Reproducibility of Results , Sensitivity and Specificity , Spectrophotometry, UltravioletABSTRACT
Data from sustained-release and enteric-coated oral formulations, and the suppository formulation of diclofenac sodium are fitted simultaneously using NONMEM and the general linear model, ADVAN 5. Absorption and disposition parameters, serum levels, and absorption profiles were determined. The in vivo absorption profiles were determined using the program TOPFIT. The in vivo absorption for the sustained-release formulation is slow first order and follows a flip-flop model since disposition rate constants are greater than absorption rate constants. Absorption from the enteric-coated form is essentially complete (> or = 95%) at about 7.5 h, while it is 95% complete at 24 h from the sustained-release formulation. This suggests likely absorption from the colon in the case of the sustained-release formulation since absorption is only 75% complete during the first 10 h. The sustained-release relative bioavailability is 90-99%. Absorption from the suppository is essentially complete at about 4.5 h. However, the relative bioavailability of the suppository formulation is low (55%), since defecation may remove the drug from the absorption site before complete absorption.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Computer Simulation , Diclofenac/administration & dosage , Diclofenac/pharmacokinetics , Models, Biological , Administration, Oral , Biological Availability , Data Interpretation, Statistical , Delayed-Action Preparations , Dose-Response Relationship, Drug , Gastric Mucosa/metabolism , Humans , Hydrogen-Ion Concentration , Suppositories , Tablets, Enteric-CoatedABSTRACT
Pharmacokinetic behavior of single dose of 2 mefenamic acid capsule formulations was studied in a randomized crossover design in 22 healthy male volunteers. Following ingestion of 250 mg of either of the products, blood samples were obtained over a 14-hour period and the serum drug concentrations were determined by an HPLC assay with ultraviolet detection at 280 nm. The parametric 90% confidence intervals of the mean value of the ratio (fendol (test)/ponstan (reference)) of pharmacokinetic parameters were 0.88-1.07, 0.94-1.19, and 0.89-1.16 for AUC zero-infinity, Cmax and T1/2. In each case values were within the acceptable bioequivalence range of 0.8-1.25. Distribution-free point estimate for the difference in expected medians of Tmax of the 2 formulations (fendol-ponstan) was -0.5 hours with a 90% confidence interval of -1.0 to -0.25 which overlaps with the stipulated bioequivalence range of +/-0.48. The kinetic parameters a comparable to what is reported for mefenamic acid and there were no statistically significant differences in any of them when comparing the 2 products by ANOVA on log-transformed data. Although the 2 products are not equivalent regarding the secondary parameter Tmax, still the data indicate that they could be considered bioequivalent regarding rate of absorption (Cmax), extent of absorption (Cmax and AUC), and elimination (t1/2).
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Mefenamic Acid/pharmacokinetics , Adult , Analysis of Variance , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Biological Availability , Capsules , Chromatography, High Pressure Liquid/methods , Cross-Over Studies , Diclofenac/blood , Humans , Male , Mefenamic Acid/administration & dosage , Mefenamic Acid/blood , Regression Analysis , Therapeutic Equivalency , Time FactorsABSTRACT
Various acyloxyethyl mefanamates were synthesized and evaluated for potential application as prodrugs. Their kinetics of hydrolysis were examined in aqueous solutions of pH 1.0 and 7.4 and in human plasma at 37 degrees C. Among the synthesized compounds, the beta-carboxypropionylethyl mefenamate and the pivaloyloxyethyl mefenamate show high stability against enzymatic and non enzymatic hydrolysis. On the other hand the acetyloxyethyl mefenamate shows t1/2s of 1.4 h, 1.41 h and 3.61 h in human plasma, solutions of pH 7.4 and pH 1.0 respectively; However, its hydrolysis to mefenamic acid in plasma was not quantitative. Preliminary in vivo study shows that acetyloxyethyl mefenamate gave plasma concentration of mefenamic acid lower than that of control after oral administration. The calculated AUC0-inf for the acetyloxyethyl and control were 45 and 85 micrograms.h/ml respectively.
Subject(s)
Mefenamic Acid/analogs & derivatives , Mefenamic Acid/chemical synthesis , Prodrugs/chemical synthesis , Acylation , Chromatography, High Pressure Liquid , Esterases/blood , Half-Life , Humans , Hydrolysis , Kinetics , Magnetic Resonance Spectroscopy , Mefenamic Acid/chemistry , Mefenamic Acid/pharmacokinetics , Molecular StructureABSTRACT
This work examines the dissolution kinetics of glibenclamide crystalline state, form I, and glibenclamide glassy state, form II. This required determination of the pH-solubility profiles of the two forms, dissolution at different stirring rates, temperatures, and pHs. It was found that form II exhibited higher solubility and dissolution rate at all the studied pHs. However, a significant increase in dissolution and solubility of form II was noted at pH 6. Dissolution studies at different stirring rates confirmed that the dissolution process is diffusion controlled, zero order in nature and adheres to the Noyes and Whitney and Levich equations. Dissolution studies at different temperatures enabled calculation of the heat of dissolution, Ea, of both forms. Ea for form I and form II was found to be almost identical. Storing of form II for one week at different temperatures resulted in the partial transformation of form II to form I as indicated from dissolution studies. The extent of transformation and hence reduction in dissolution rate increased with the increase in storage temperature.
Subject(s)
Glyburide/chemistry , Buffers , Crystallization , Hydrogen-Ion Concentration , Kinetics , Solubility , ThermodynamicsABSTRACT
This study investigates the kinetics of the release of indomethacin from Eudragit RS polymer. It involved the study of the dissolution behaviour of indomethacin from different combinations of the drug in a solid dispersion form, granules and physical mixtures. It was evident that Eudragit RS had a retardation effect on the release of indomethacin, this effect was dependent on the amount of Eudragit included. Inclusion of sodium lauryl sulphate (SLS) in the solid dispersion, granules and physical mixtures modified the release and made it comparable to the release from Indocid retard capsules. The kinetics of the release process was found to be best described by the Higuchi square root of time equation and the first order equation indicating that the release process is diffusion controlled and dependent on the initial drug concentration. The retarding effect Eudragit had on the release of indomethacin was attributed to the possible interaction of the ammonium groups of the polymer with the carboxylate anion of indomethacin and to the inclusion of the drug within the inert insoluble polymer matrix.
Subject(s)
Acrylic Resins , Indomethacin/chemistry , Capsules , Delayed-Action Preparations , Gels , Kinetics , Polymethacrylic Acids , Sodium Dodecyl Sulfate , SolubilityABSTRACT
Bioequivalency of Omeraz, a test-product of Arab Pharmaceutical Manufacturing Company (Jordan) and Losec, a reference product by Astra (Sweden), was evaluated by a randomised crossover study on 22 healthy male volunteers. Serum concentrations of omeprazole were measured by an HPLC assay. There were no statistically significant differences between the two products in terms of serum profile and pharmacokinetic parameters including AUC, Cmax, Tlag, Tmax, MRT, Ke and T1/2. The AUC ratios (Omeraz/Losec) for 24 hours and for infinity were respectively 1.02 with a 90% C.L. of 0.88-1.16 and 1.00 with a 90% C.L. of 0.88-1.14. The two products may be considered as bioequivalent in terms of the extent of absorption as indicated by the AUC ratios. However, the confidence limits of Cmax fall outside the FDA accepted range.
Subject(s)
Omeprazole/pharmacokinetics , Administration, Oral , Adult , Capsules , Chromatography, High Pressure Liquid , Cross-Over Studies , Humans , Male , Omeprazole/administration & dosage , Omeprazole/blood , Random Allocation , Therapeutic EquivalencyABSTRACT
The pharmacokinetic parameters (AUC0-8h, AUC0-infinity, Cmax, tmax, t1/2, Ke) of cefuroxime following a single intramuscular injection of 750 mg of a test product (Maxil, Hikma Pharmaceuticals, Amman, Jordan) were compared to those of a reference product (Zinacef, Glaxo, UK). The 2 products were administered according to a randomized 2-way crossover design to 26 healthy male volunteers. Cefuroxime plasma concentrations were determined using a rapid, sensitive and precise HPLC method with UV detection at 280 nm. The means of the ratios AUC0-infinity Maxil/AUC0-infinity Zinacef and Cmax Maxil/Cmax Zinacef were close to 1 and their 90% confidence intervals included 1. The mean pharmacokinetic parameters of the 2 products were not different and their 90% confidence intervals overlapped. The 2 products were not statistically different with respect to both rate and extent of absorption as demonstrated by statistical analysis on Cmax, tmax, AUC0-8h and AUC0-infinity. The 2 products were also similar regarding t1/2 and Ke. The ANOVA analysis showed no differences in the pharmacokinetic parameters of the 2 products in relation to treatment, sequence of product administration or the interaction term. Pharmacokinetic parameters of cefuroxime were comparable to reported values. We conclude that the 2 products of cefuroxime (Maxil and Zinacef) are bioequivalent.
Subject(s)
Cefuroxime/pharmacokinetics , Adult , Analysis of Variance , Biological Availability , Cefuroxime/administration & dosage , Cefuroxime/blood , Chromatography, High Pressure Liquid , Computer Simulation , Cross-Over Studies , Drugs, Investigational , Humans , Injections, Intramuscular , Male , Reference Standards , Therapeutic EquivalencyABSTRACT
A single dose pharmacokinetic study was conducted on two sustained-release formulations (75 mg) of indomethacin (Indocid capsules 'A' and Indogesic tablets 'B'). The study was carried out on 22 healthy male volunteers, who received a single oral dose (75 mg) of each product according to a randomized crossover design. Blood samples were obtained over a 24 h period, and drug concentrations were determined by an HPLC assay. The two products were not found to be statistically different with respect to the lag time between dosing and first appearance of the drug in the serum (1.0 +/- 0.1 and 0.9 +/- 0.1 h for A and B, respectively), or in the time needed to attain the peak concentrations (3.3 +/- 0.3 and 3.3 +/- 0.5 h for A and B, respectively). The two products, however, varied significantly in the peak serum concentrations (2721 +/- 220 and 1797 +/- 129 ng/ml for A and B, respectively). In terms of the extent of absorption, assessed by estimating the area under the concentration-time curve over 24 h, the two products were not found to be significantly different (11,575 +/- 630 and 10,212 +/- 556 ng . h/ml for A and B, respectively). Based on these findings, the two formulations can be considered bioequivalent in the extent but not in the rate of drug absorption.
Subject(s)
Indomethacin/administration & dosage , Indomethacin/pharmacokinetics , Adult , Capsules , Chromatography, High Pressure Liquid , Delayed-Action Preparations , Humans , Indomethacin/blood , Male , TabletsABSTRACT
A single dose comparative bioavailability study and an in vitro evaluation were conducted on two sustained-release formulations of diclofenac sodium (Voltaren "V" and Diclogesic "D"). The two products were found similar in weight and content uniformity. The in vitro dissolution, however, revealed that product D has a significantly faster rate of drug release compared to product V. The bioavailability study was carried out on 15 healthy male volunteers, who received a single oral dose (100 mg tablet) of each product according to a randomized crossover design. Blood samples were obtained over a 12 h period, and drug concentrations were determined by an HPLC assay. The two products were not found to be statistically different with respect to the lag time between dosing and appearance of the drug in the serum (0.8 +/- 0.2 and 0.6 +/- 0.1 h for V and D, respectively), or in the time needed to attain the peak concentrations (4.5 +/- 0.8 and 4.1 +/- 0.9 h for V and D, respectively). The two products, however, varied in the peak serum concentration (736 +/- 125 and 536 +/- 63 ng.ml-1 for V and D, respectively), but this difference was not statistically significance. In terms of the extent of absorption, assessed by estimating the area under the concentration-time curve over 12 h, the two products were not significantly different (3,340 +/- 270 and 3,045 +/- 294 ng.h.ml-1 for V and D, respectively). These in vitro and in vivo findings indicate that Diclogesic is characterized by sustained-release properties which are comparable to Voltaren.
Subject(s)
Diclofenac/pharmacokinetics , Administration, Oral , Adult , Biological Availability , Chromatography, High Pressure Liquid , Delayed-Action Preparations , Diclofenac/administration & dosage , Diclofenac/chemistry , Drug Tolerance , Humans , MaleABSTRACT
A comparative bioavailability study and in vitro characterization were conducted on two commercial products of diclofenac sodium (Voltaren "A" and Inflaban "B") in the form of enteric-coated tablets (25 and 50 mg). The two products were found similar in weight variation and content uniformity and both met the British Pharmacopeia requirements of disintegration for enteric-coated tablets. The dissolution in vitro revealed that product B was characterized by a faster rate compared to product A. The bioavailability of single doses, 2 x 50 and 2 x 25 mg, of each product was carried out respectively, on 14 and 6 normal male volunteers, according to a randomized complete block design. Blood samples were obtained over a 12-hour interval and serum concentrations of the drug were determined using an HPLC assay. The two products were found bioequivalent as assessed by AUC. However, the tmax value was found to be significantly smaller for product B compared to product A indicating that product B is apparently absorbed at a faster rate. Further, product B was characterized by higher Cmax values, although these were not statistically different from the corresponding values of product A. These findings are consistent with the in vitro dissolution pattern of the two products, and the differences in the rate of absorption may have therapeutic implications.