ABSTRACT
In this study cost effective direct compression technique was used for the development and optimization of intermediate release [IntR] ketoprofen tablets using central composite design [CCRD]. Fifteen different formulations [F1-F15] were developed using [X[1]] microcrystalline cellulose [Avicel PH-102] [18-51%], [X[2]] methocel K4M [0.1- 25%] and [X[3]] starch [1.5-18%] as selected variables while responses were % friability and Carr's Index [compressibility index]. Powder blends of all formulations were evaluated using Angle of Repose, Carr's Index and porosity. Results of powder blends comply with USP standards and are classified as Fair Excellent. From F1-F15 only four formulations i.e. F6, F7, F14 and F15 were selected on acceptable weight basis, micromeritic properties and on the concentration of excipients. For the assessment of physico chemical properties of the optimized formulations different tests were performed. All results were found to be adequate range. In vitro assessment of the optimized formulations were also carried out in different dissolution media i.e. pH 1.2, phosphate buffer 4.5, pH 6.8 and pH 7.5. Release behaviour of F6, F7, F14 and F15 were estimated by using one - way ANOVA, model - independent, model dependent methods. Results of f1 and f2 showed that all the test formulations i.e. F6, F7, F14 were found to be similar with the reference formulation i.e. F15 at various dissolution media. Also all the formulations followed Hixson-Crowell kinetic model. The parameter n showed Anomalous transport [non - fickian diffusion]. The mean dissolution time [MDT] was found to be in the range of 2.632-2.922. Results of ANOVA indicated no significant difference within and between formulations at different dissolution media as p values were found to be >0.05. Also all the selected formulations were found to be stable at accelerated conditions
ABSTRACT
A Simple, sensitive and accurate high-performance liquid chromatographic [HPLC] method for effective and specific analysis of Loxoprofen [LXP] in the mobile phase and human plasma was developed. Effective chromatographic separation was attained on a Mediterranea Sea C18 column [250×4.6mm, 5um] with mobile phase containing acetonitrile and 0.01 M NaH2PO4 buffer [55: 45] by adjusting pH 6.5 with sodium dihydrogen phosphate buffer at a flow rate of 1ml/ min. Calibration ranges from 0.1ppm to 10 ppm with a coefficient of relation value [R2=0.999] by using a linear regression method and lower limit of quantification was 0.1ppm. The current method showed inter-day and intra-day accuracy and precision within the range of +/- 10%. % RSD was found to be less than 5 %. Analytical recovery was more than 90% which confirmed the reliability of current method. The proposed method was found appropriate for assessment of LXP in pharmacokinetic and bioequivalence study
ABSTRACT
A swift, precise and simple HPLC bioanalytical technique with UV detection was established and validated for quantitative estimation of valsartan in human plasma. The analyte was separated from plasma by protein precipitation with acetonitrile and chromatographically separated on Zorbax SB-C18 [5 micro m, 4.6mm x 15cm] column. The solvent mixture system consisting of acetonitrile, water and glacial acetic acid [40:59:1 v/v], was pumped using isocratic mode at 1mL/min flow rate. Samples' detection of drug was made spectrophotometrically at a wavelength of 264nm. The analyte response was instituted to be linear from 0.06 to 8 micro g/mL with a regression value of 0.999. The accuracy of the proposed method was ranged between 97.2-100.3% with 5% RSD. The analytical recovery [>95%] was consistently observed and satisfactory sample stability was also found at different environmental conditions. In conclusion the reported bio-analytical method is easy and robust that was successfully utilized in estimation of valsartan in a pharmacokinetic study
ABSTRACT
The objective of this study was to assess the quality of six different brands of enteric coated Ketoprofen 100 mg tablets, KPB[2] to KPB[6] are available in commercial market of Karachi, Pakistan, while KPB[1] was obtained from international source. We performed different physico-chemical assessments i.e. weight variation, diameter, hardness, friability, thickness, disintegration, content uniformity, assay and dissolution test. Results of all the investigations were found to be in adequate limits. Also pharmaceutical equivalence was determined by selecting different tests and assay assessment. Furthermore, in vitro therapeutic equivalence was also estimated at phosphate buffer pH 6.8 and 7.5. Results were evaluated by one way ANOVA, model independent and model dependent methods. ANOVA results showed that release behaviour were found to be similar as p values >0.05, also KPB[1] - KPB[6] followed Weibull model at different dissolution media. Results indicated that innovator and brands not only passes the pharmaceutical equivalence assessment but also comply with the in vitro therapeutic equivalence
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/standards , Tablets, Enteric-Coated , Drug Compounding , Quality Control , Models, Chemical , PakistanABSTRACT
In the present study the pharmacokinetic and bioequivalence parameter of Ketoprofen 100 mg fast dispersible tablets [test] were measured with marketed [reference] product. This study was accomplished following PDA guidance. A single dose, open labeled, cross over [two way], randomized study design was used to conduct investigation on 12 Pakistani healthy volunteers. At various time points blood samples [l0mL] were drawn i.e. at 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12 and 13hr. Plasma was then separated and ketoprofen concentrations were estimated by validated HPLC technique using LC 20A pump [Shimadzu Corp, Japan] and Spectrophotometric SPD-20Adetector [Shimadzu Corp, Japan]. Ketoprofen concentrations were then analyzed by Kinetica[TM] 4.4.1 [Thermo electron corp, USA] to estimate various compartmental and noncompartmental pharmacokinetic parameters. Various parameters of bioequivalence including AUC,o,, AUCo-oo, AUC/os,, Tmaxcaic and C[maxcaic]w ere compared using ANOVA method [two way]. For log and non-log transformed data the 90 % confidence interval values for AUC [1.0087-1.0704; 1.0099-1.0714], AUC[to], [0.95482-1.0093; 0.95486-1.0098], AUC[last] [0.93373-0.98605; 0.93404-0.98603], C[maxcaic] [0.92978-0.9955; 0.92962-0.99663] and maxcaic [0.89019-0.94116; 0.89095-0.94288] for test and reference products respectively. Results were found to be within the PDA satisfactory range. For the results verification, Schuirman's one sided / test was used. SPSS 17.0 [SPSS Inc] was utilized for the determination of wilcoxon sign rank test. Results showed no carry over effect after first study period. Also test product met the regulatory criteria for bioequivalence with the reference product. Both the formulations were well tolerated
Subject(s)
Humans , Anti-Inflammatory Agents, Non-Steroidal , Healthy Volunteers , Analysis of Variance , Therapeutic Equivalency , TabletsABSTRACT
Meropenem is a restricted, broad spectrum and expensive antibiotic
The major consequences of irrationa of restricted antibiotics are increase drug resistance and drug expenditure
The use of antibiotics, specifically restr antibiotics, must be monitored continuously to increase its adherence to the standard guidelines to avoid such probl
The objective of this study was to evaluate the appropriateness of meropenem use with respect to renal status of pat in a teaching based hospital. A retrospective study was carried out from 1st January 2013 to 30th June 2013 to deten the evaluation of meropenem use in accordance to the criteria developed through national [Infectious disease sociel Pakistan] and international guidelines [Health care infection control practices advisory committee]. The data recorded on data collection form by thorough reviewing of patients' medical records. Main outcomes measured indication, dose, interval, duration, creatinine clearance, complete blood count and culture sensitivity test
Correlatio different variable [side effects and generalized health] was also observed with reference to renal status of patit Statistical analyses were performed using descriptive statistics
A total of 201 cases of meropenem prescription identified during the study period
The variable, which was most consistent with the criteria was 'indication', in wl 97.52% of meropenem prescription was indicated in diseases encouraged by guidelines. However, the use of meropei as an empirical therapy was the major problem reported in this study as it adhered to in only 43% of the cases. It also noted that prevalence of side effects increased when meropenem was prescribed in renal compromised patients, also observed that generalized health of patients decreased with meronem use in renal unstable patie Thrombocytopenia was the major problem associated with the meropenem use [37.81%]
The study detected vari areas where use of meropenem was not according to the standards. Strict policies and procedures need to implemented to use meropenem in line with the standard guidelines
ABSTRACT
A high-pressure liquid chromatography [HPLC-UV] based simple and specific method for simultaneous quantitative determination of aspirin, amlodipine besylate and simvastatin in a capsule formulation has been developed and validated according to ICH guidelines
Chromatographic separation of the three drugs was carried out by aSpherisorbODS2 reverse phase column [4.6 x 250 mm; 5 microm] using amobile phase, which consisted of 70: 30 [v/v] mixture of acetonitrile and triethylamine phosphate buffer [pH 3; 0.015 M] with final pH adjusted to 2.5 using dilute ortho-phosphoric acid, at a flow rate of ImL/min. The eluents were detected at UV wavelength of 237 nm and the retention times for aspirin, amlodipine besylate and simvastatin were -2.7 mins, -6.1 mins and 10.5mins, respectively. This method is suitable and specific for the three drugs and was found to be linear [R[2]>0.995], accurate, specific, reproducible and robust in the concentration range of 375 to 1125mcg/ml for aspirin, 25 to 75mcg/ml for amlodipine besylate and 50 to 150mcg/ml for simvastatin. This simple and convenient method could be easily utilized for the characterization and quantitation of the three drugs in a single formulation for combination therapy of cardiovascular diseases