Development and Quality evaluation of sustained release pellets of eperisone HCl.

The objective was to develop eperisone HCl sustained-release pellets through extrusion spheronization technique and to determine the influence of different hydrophobic (polymeric based and wax-based) and hydrophilic (polymeric based) matrix former on the release of eperisone HCl (BCS class I drug) and on pellet sphericity. The pellet formulations consisted of different hydrophobic and hydrophilic matrix formers like HPMC K4M (10-20%) HPMC K15M (10%), EC (7cps) (10-20%), Carnauba wax (10-20%), Compritol ATO 888 (10-20%), Glyceryl monostearate (10%), lactose and microcrystalline cellulose. The initial burst release of the drug from matrix pellet formulations was effectively controlled by coating with 5% EC (ethylcellulose) dispersion. The dissolution profile and drug release kinetics of coated pellet formulations were determined at both acidic and basic pH medium. SEM (Scanning electron microscope) technique was used to determine the surface morphology and cross-section of F5 and F7 pellet formulation. The mechanism of drug release of coated formulation followed non-Fickian diffusion. FTIR spectroscopy was conducted and no drug and excipients interaction was observed. The results had shown that optimized coated formulation was F5 and F7 which effectively extend the drug release for 12 hours.

Modification and validation of liquid chromatographic method for the quantification of ciprofloxacin in human plasma and its application to a bioavailability study.

A new simple, accurate, precise and sensitive liquid chromatographic method for the analysis of Ciprofloxacin in human plasma, suitable for quantification of drug was developed and validated using HPLC-UV method. The analyte was chromatographically separated from endogenous plasma components on a C-18 reversed phase column (5µm, 25cm × 0.46cm) and detected at 278nm. The sample pretreatment was carried out with acetonitrile on 200µl of plasma. The Lower limit of quantification (LLOQ) was 0.04 µg/ml with linearity in the range 0.04-4 µg/ml and coefficient of correlation value (R2)>0.995. The method was successfully validated as per current FDA guidance for necessary parameters and applied to a pilot bioavailability study conducted on six healthy volunteers with marketed Ciprofloxacin 250mg immediate release tablets. The plasma concentrations were subjected to non-compartmental analysis for calculation of pharmacokinetic parameters like Cmax, Tmax, AUCo-t, AUC 0-∞ and t½ etc. The mean values of Cmax and Tmax were found to be 1.35±0.09µg/ml and 1.25±0.27h respectively while for other pharmacokinetic parameters including AUCo-t, AUC0-∞ were found to be 5.98±0.96 µg/ml×h and 6.34±1.07µg/ml×h. The drug exhibited half-life (t½) of 3.94±0.33h. The obtained results proved the suitability of the method for routine pharmacokinetic studies of Ciprofloxacin.

HPLC-UV method for simultaneous quantitation of artemether and lumefantrine in fixed dose combination orodispersible tablet formulation.

This paper describes the development and validation of a high performance liquid chromatography (HPLC-UV) method for the simultaneous quantitative determination of artemether and lumefantrine in fixed dose combination tablets. Chromatographic quantitation was carried out on a C-18 column Mediterrania Sea 18 (250×4.6 mm i.d.; 5 µm particle size) using a mobile phase consisting of 80:20 v/v mixture of acetonitrile and 0.05 % trifluoroacetic acid with final pH adjusted to 2.35 at flow rate of 1 ml/minute. The eluents was detected using photo diode array detector at wavelength of 210nm for artemether and 286 nm for lumefantrine. The retention times were ~5.8 mins for artemether and ~7.3 mins for lumefantrine. The newly developed method was validated and was found linear (r2 >0.99), precise (R.S.D. <2.0%), accurate, specific and robust. The artemether contents in the tablet formulation varied from 99.026 % to 99.347%, while lumefantrine contents were 99.546-99.728 %.

Comparative pharmacokinetic evaluation of extended release itopride HCl pellets with once daily tablet formulation in healthy human subjects: a two treatment, four period crossover study in fasted and fed condition.

OBJECTIVE: In this study, pharmacokinetics (PKs) and bioavailability of newly developed extended release (ER) Itopride HCl 150 mg encapsulated ER pellets (test) and 150 mg Ganaton ER once-daily (OD) tablets (reference) were compared and evaluated under fasted and fed conditions. METHODS: Twelve healthy human subjects were enrolled in a single dose, randomized; two treatments, two sequences, four period crossover study. A modified and validated liquid chromatographic method was used for the estimation of Itopride HCl in plasma samples. The data were analyzed through non-compartmental model using PK software Phoenix Winnonlin version 7. The outcome was measured on logarithmically transformed data, where p > 0.05 was considered as non-significant with 90% CI limit of 0.8-1.25. RESULTS: The Cmax, AUC0-t, and AUC0-∞ values of Itopride HCl 150 mg ER pellets versus that of OD 150 mg tablets, in fed and fasted states, were within the limits specified by FDA to establish bioequivalence. The relative bioavailability of Itopride HCl 150 mg ER pellets were 1.019 (fed) and 1.081(fasted). The 90% CIs of AUC values for Itopride HCl 150 mg ER pellets and OD 150 mg tablets in fed versus fast were significantly greater and were not within 80-125% limit. CONCLUSION: The test and reference formulations had similar pharmacokinetic parameters in each condition studied. However, an increase in the amount of drug was observed in the fed state.

Formulation development and in vitro evaluation of fast dispersible, taste masked aceclofenac compacted pellets.

The objective of study was to develop Aceclofenac fast dispersible compacted pellets with improved taste and fast drug release. Pellets were prepared by extrusion spheronization technique followed by direct compression to make compacted pellets. Formulations were comprised of sucrose, mannitol, ac-di-sol, aspartame, pine apple flavor and magnesium stearate. A mixture of distilled water and isopropyl alcohol (1:1) was used for wet massing. The effect of ac-di-sol on the drug release pattern was examined and dissolution profile comparison was established. All formulations followed First order and Weibull models and f2 values indicated dissimilarity with the marketed immediate release product. Taste of compacted pellets was evaluated by a panel of 12 human volunteers. Formulation P5 was found to be an optimized formulation due to satisfactory quality attributes.

Effect of lipid and cellulose based matrix former on the release of highly soluble drug from extruded/spheronized, sintered and compacted pellets.

BACKGROUND: The study was to develop an extended release (ER) encapsulated and compacted pellets of Atenolol using hydrophobic (wax based and polymeric based) and high viscosity grade hydrophilic matrix formers to control the release of this highly water soluble drug by extrusion/spheronization (ES). Atenolol is used for cardiovascular diseases and available as an immediate release (IR) tablet dosage form. The lipids, Carnauba wax (CW), Glyceryl monostearate (GMS) and cellulose based i.e. Hydroxypropyl methylcellulose (HPMC) and Ethyl cellulose (EC) were used in preparing Atenolol ER pellets. Thermal sintering and compaction techniques were also applied to control the burst release of Atenolol. METHOD: For this purpose, thirty-six trial formulations (F1-F36) were designed by Response Surface Methodology (RSM), using Design-Expert 10 software, keeping (HPMC K4M, K15 M & K100 M), (EC 7FP, 10FP & 100FP), waxes (GMS, & CW), their combinations, sintering temperature and duration, as input variables. Dissolution studies were performed in pH, 1.2, 4.5 and 6.8 dissolution media. Drug release kinetics using different models such as zero order, first order, Korsmeyer-Peppas, Hixon Crowell, Baker-Lonsdale and Higuchi kinetics were studied with the help of DDsolver, an excel based add-in program. RESULTS: The formulations F35 and F36 showed compliance with Korsmeyer-Peppas Super case II transport model (R2 = 0.975-0.971) in dissolution medium pH 4.5. No drug excipient interaction observed by FTIR. Stereomicroscopy showed that sintered combination pellets, (F35), were highly spherical (AR = 1.061, and sphericity = 0.943). The cross-sectional SEM magnification (at 7000X) of F34 and F35 showed dense cross-linking. The results revealed that the optimized formulations were F35 (sintered pellets) and F36 (compacted pellets) effectively controlling the drug release for 12 h. CONCLUSION: Extended-release encapsulated, and compacted pellets were successfully prepared after the combination of lipids CW (10%) and GMS (20%) with EC (10FP 20% & 100FP 20%). Sintering and compaction, in addition, stabilized the system and controlled the initial burst release of the drug. Extended release (ER) Atenolol is an effective alternative of IR tablets in controlling hypertension and treating other cardiovascular diseases.

Prescribing pattern of angiotensin receptor blocker: A study of errors and drug-drug interactions.

Prescriptions comprising multi-drug therapy mostly illustrate the prescribing error. The phenomenon of error is bonded with human inaccuracy. The erroneous practice is observed in under developed countries like Pakistan, Bangladesh and also in developed ones. Consequently drug-drug interaction is one of the most common error associated with potentially serious adverse response even death. Accordingly the present study was conducted to assess the prevalence of prescribing errors and drug-drug interactions in out-patients receiving angiotensin receptor blockers. The study was done with population size one hundred fifty prescriptions obtained from different out-patient settings in Karachi. The prescriptions were screened for prescribing errors and risk factors for drug-drug interactions. Drug-drug interactions were recognized by Micromedex.2.0.Drug-Reax®database. The most common type of error was omission error. These errors were patient's age, weight and diagnosis found in 51.3%, 97.3% and 74% of prescriptions, respectively. The prevalence of drug-drug interaction was 38%. A total of 746 drugs were prescribed with an average of 5 drugs per prescription and 450 medication errors were detected. Majority of the interaction were moderate (19.33%), others were minor (14%) and major (6%) in severity. Patients who prescribed many drugs (more than 5 drugs in a while) had a higher risk of developing drug-drug interactions (OR=4.76; 95% CI=2.30-9.64; p=0.0001*).The study data reports the occurrence of prescribing errors in Karachi and also necessitate the need of clinical pharmacist's services in health care system. The step will help to minimize the risk factors by having the drug prescriptions reviewed by the pharmacists.

Development and optimization of intermediate release ketoprofen tablets by central composite design.

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 (X1) microcrystalline cellulose (Avicel PH-102) (18-51%), (X2) methocel K4M (0.1-25%) and (X3) 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.

Development and validation of liquidchromatographic method for quantitative determination of Loxoprofen in mobilephase and in human plasma.

A Simple, sensitive and accurate high-performance liquid chromatographic (HPLC) method for effective and specific analysis of Loxoprofen (LXP) in the mobilephase and human plasma was developed. Effective chromatographic separation was attained on a Mediterranean Sea C18 column (250×4.6mm, 5um) with mobilephase 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.

Out of pocket (OOP) cost of treating hypertension in Karachi, Pakistan.

Pakistan is categorized to below to middle income countries where two third of the national annual health expenditure is in the form of out of pocket (OOP) cost. A prevalence based study was conducted to determine the OOP cost treatment of hypertension in Karachi by interviewing 350 hypertensive patients aged >30 years through a validated questionnaire. Hypertension (HTN) was classified into stage 1 and stage 2 and was found to be common in females (53.42%) than males (46.57%). The total costs of stage 1and stage 2 HTN were calculated to be 217869.7PKR and17545457.6 PKR respectively. The average treatment cost of stage 1 was observed to be significantly lower (p=0.006) than the cost of stage 2 HTN. Moreover; the cost of antihypertensive drugs, physician fees and laboratory tests were considerably different however; no variation was seen in cost of transport and loss of productivity through absenteeism from work. Overall, the present study indicates that the antihypertensive treatment has imposed a high burden on the pocket of common man and this is a major reason for treatment non-adherence. Consequently, it increases the risks of cardiovascular events, morbidity and mortality. Therefore, effective strategic planning is need of time to reduce OOP cost for better control on hypertension in Pakistan.

Development and validation of RP- HPLC method with UV detection to determine and quantify dimenhydrinate in human plasma.

A simple, sensitive and rigorous method for estimation of dimenhydrinate in human plasma was searched and its validation was carried out. LLE (Liquid-Liquid extraction) of analyte with mixture of Hexane and ethyl acetate (1:1 v/v) was carried out for the preparation of Plasma Samples, Chromatographic elution of dimenhydrinate was conducted in human plasma and mobile phase with C-18 bonda Pack column (10µm; 250 × 4.6), using a mobile phase consisting a solution of ammonium bicarbonate in water and methanol at a flow rate of 0.5ml/minute with UV detection at 229 nm. The resolution of dimenhydrinate was well performed from plasma components. This method was validated and exhibited linearity with concentration range of 6 to 380ng/ml of dimenhydrinate in plasma. The Intra day precision was 89.2 to 96.89% and Inter day precision was 88.6% to 93.26%, the average recovery of dimenhydrinate was 97.02%. The efficacy of extraction was proved by above mentioned results. 2ng/ml and 6ng/ml, were appraised as the LOD and LOQ of dimenhydrinate, stability studies disclosed that dimenhydrinate exhibited stability in Plasma after Freeze & thaw cycles and upon -20°C storage, the method was developed well.

Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent-Meclizine HCl.

BACKGROUND: Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated. METHODS: Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol®), Glyceryl palmitostearate (Precirol®), Glyceryl behenate (Compritol®) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found. RESULTS: Sphericity indicated by shape factor (eR) varied with type and concentration of lipids: Geleol® (eR = 0.891-0.997), Precirol® (eR = 0.611-0.743), Compritol® (eR = 0.665-0.729) and Carnauba wax (eR = 0.499-0.551). Highly spherical pellets were obtained with Geleol® (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol® and Compritol®, (ii) Geleol® and Carnauba wax and (iii) Geleol®, Compritol® and Carnauba wax. Scanning electron microscopy of Compritol® pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol® and Compritol® pellets, explained by Korsmeyer-Peppas (R2 = 0.978-0.993) indicated non-Fickian diffusion (n = 0.519-0.597). Combinations of (ii) Geleol® and Carnauba wax and (iii) Geleol®, Compritol® and Carnauba wax pellets followed Zero-order (R2 = 0.991-0.995). Similarity test was performed using combination of Geleol® and Compritol® (i) as a reference. CONCLUSIONS: Matrices for the extended release of Meclizine HCl from extruded-spheronized pellets were successfully formed by using three lipids (Geleol®, Compritol® and Carnauba wax) in different combinations. The encapsulated pellets of Meclizine HCl can be effectively used for treatment of motion sickness, nausea and vertigo for extended period of time.

PHARMACOKINETICS AND BIOEQUIVALENCE STUDIES OF TWO NIMESULIDE 100 mg TABLETS: UNIT DOSE, RANDOMIZED-SEQUENCE, TWO-WAY CROSSOVER STUDY IN HEALTHY VOLUNTEERS OF PAKISTANI POPULATION.

Single centered crossover, two cycles volunteer study was performed on 12 healthy male volunteers. Both reference and test, immediate release nimesulide formulation was given in a randomized manner with a washout period of 15 days and 5 mL of blood samples were drawn at 0.5, 1, 1.5, 2, 4, 8, 12 and 24 h. Plasma after centrifugation and deproteination, 100 µL of the sample was injected using already validated HPLC method. In plasma LOQ was 0.01 ± 0.012 µg/mL, LOD was 0.001 µg/mL and linearity was observed from 10 to 0.001 pg/mL. Pharmacokinetic parameters including in vivo bioequivalence were studied by using Kinetica 4.4.1. software. The average values of AUC,, was found to be 23.654 ± 0.688 and 23.532 ± 0.662 mg/L x h while C.. values were 6.101 ± 0.403 and 6.072 ± 0.403 pg/mL, respectively. Mean clearance and volume of distribution of reference formulation were 64.062 ± 3.086 mL/h/kg and 9.416 ± 4.767 L, respectively. The disposition rate constant in reference formulation was 0.339 ± 0.598 h' while in immediate release it was 0.467 ± 0.481 h-'. Absorption rate constant and distribution rate constant for reference brand were 1.409 ± 0.251 h- and 1.201 ± 0.283 h' while in immediate release formulation these values were 1.420 ± 0.214 h-' and 1.227 ± 0.263 h', respectively. Bioequivalence results showed 90% confidence of interval for compartmental parameters like Cmax was 99.1 to 100.3%, Tmax. was 98.198 to 99.658% and AUClast, was 99.88 to 100.08% and all were within range.

Pharmacokinetic and bioequivalence studies of fast dispersible ketoprofen tablets in healthy volunteers.

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 FDA 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 (10mL) 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 KineticaTM 4.4.1 (Thermo electron corp, USA) to estimate various compartmental and noncompartmental pharmacokinetic parameters. Various parameters of bioequivalence including AUCtot, AUC0-oo, AUClast, Tmaxcalc and Cmaxcalcw ere compared using ANOVA method (two way). For log and non-log transformed data the 90% confidence interval values for AUC oo0-oo, (1.0087-1.0704; 1.0099-1.0714), AUC tot , (0.95482- 1.0093; 0.95486-1.0098), AUClast (0.93373-0.98605; 0.93404-0.98603), Cmaxcalc (0.92978-0.9955; 0.92962-0.99663) and Tmaxcalc (0.89019-0.94116; 0.89095-0.94288) for test and reference products respectively. Results were found to be within the FDA satisfactory range. For the results verification, Schuirman's one sided t 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.

Pharmaceutical and in vitro therapeutic equivalence studies of ketoprofen enteric coated 100 mg tablets.

The objective of this study was to assess the quality of six different brands of enteric coated Ketoprofen 100 mg tablets, KPB2 to KPB6 are available in commercial market of Karachi, Pakistan, while KPB1 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 - KPB6 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.

Development and validation of HPLC method for the determination of Cefpodoxime Proxetil in human plasma.

A new, simple, accurate, precise and specific method has been developed for the analysis of Cefpodoxime Proxetil in human plasma. The proposed method was developed and validated with the aim to be used in Bioavailability/Bioequivalence studies for quantification of drug in human plasma. The mobile phase components were acetonitrile, methanol, and water in the ratio of 20:50:30. Ortho phosphoric acid was used to adjust at pH5.0. Flow rate and wavelength were kept 1ml/min and 247nm respectively. The column was C-18 HPLC column 5um particle size, L x 1.d. 25cm x4.6mm. (Supelcosil). Retention time of Cefpodoxime Proxetil was found to be 10.967min. The developed method was validated for selectivity, recovery, accuracy, precision, repeatability, reproducibility, stability and linearity in the range of 0.195mcg/ml to 50mcg/ml. The accuracy and Precision of the proposed method were well within the predefined limits i.e. ±15% for all the calibration standards other than LLOQ (Lower Limit of Quantification) where it was well within ±20% of the nominal value. The analytical recovery was always above 89% showing satisfactory recovery. The coefficient of correlation (R2 ) was 0.999. The developed method was found suitable for the estimation of Cefpodoxime Proxetil in plasma.

Quality surveillance of immediate release aceclofenac tablets (100 mg) available in local market.

Aceclofenac is considered to be an effective drug that has been widely prescribed for multi-medical complaints globally. Owing to high demand many generic counterpart of aceclofenac tablets are now available in the commercial market. The aim of the present work is to evaluate and compare the quality attributes of various national/local brands of aceclofenac immediate release tablets (100mg) with the standard multi-national brand available in Pakistan. Physico-chemical evaluation was performed by determining the average tablet weight, thickness, hardness, disintegration time, percent dissolution and assay. Moreover, brands and reference formulation were exposed to multipoint dissolution. The in vitro drug release pattern was examined in various pH environment (1.2, 4.5 and 6.8) using USP dissolution apparatus 2 (paddle) at 50 rpm. The data was then analyzed by model dependent (Zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer & Peppas, and Weibull model), pair wise procedure (f1 & f2) and one-way ANOVA methods. Results showed that the all aceclofenac brands and the reference tablets followed Weibull kinetics at pH 6.8. f1 & f2 were also found to be within the acceptable FDA limits. Furthermore, the values of One-way ANOVA also confirmed the absence of any significant difference among various aceclofenac brands.

HPLC method development and validation for the determination of Cefaclor in human plasma.

Cefaclor was analyzed in the human plasma by developing a simple, precise and accurate assay method which was then validated for its accuracy, specificity and precision. The mobile phase comprised of a mixture of sodium 1-pentanesulfonate, water, triethylamine and methanol. Phosphoric acid was used to adjust the pH to 2.5±0.1. The flow rate was maintained at 1.5ml/min and the wavelength was set at 265 nm. A C-18 HPLC, column 5um particle size, L x 1.D. 25cm x 4.6mm (Supelcosil) was utilized for chromatographic separation. The retention time of Cefaclor was found to be 17min. This method was validated for selectivity, accuracy, precision, repeatability, reproducibility, recovery, linearity, and stability. Calibration curves were found linear were in the range of 0.39µg/ml to50µg/mland the coefficient of correlation (R2) was found to be 0.999. Hence, this method has been found useful for the determination of Cefaclor in plasma.

Development & validation of reversed phase HPLC method for quantification of water insoluble API.

In the present work a specific, accurate, precise, and reproducible UV-HPLC method was developed and validated for the analysis of Aceclofenac. This method involved elution of Aceclofenac in a mobile phase which is composed of buffer pH 6.8 (i.e. using 0.01N KH2PO4) and HPLC grade Acetonitrile (60:40). Separation of the analyte was achieved using HPLC isocratic pump attached to the UV-VIS detectorC18, guard column and C18 column. The injection volume was 20µL, detected at 274 nm; flow rate: 1mL/min. Standard calibration curve was measured and found linear from 0.1 to 40µg/ml. The validation parameters were measured according to FDA guidelines and successful results were obtained. The presented analytical method could be employed for pharmacokinetic studies.

Impact of different organic acids on solubility enhancement of cefpodxime proxetil immediate release tablet and its stability studies.

Cefpodoxime proxetil is a third generation cephalosporin antibiotic demonstrates pH dependent solubility and is highly soluble only in acidic pH. The purpose of this investigation was to design and develop immediate release tablets of cefpodoxime proxetil by direct compression method and determine the effect of different solid buffers (organic acids) such as fumaric acid (formulations F1-F4), maleic acid (formulations M1-M4) and citric acid (formulations C1-C4) by using cefpodoxime and acid in the ratios of 4:1, 2:1, 1:1 and 1:2 to achieve pH-independent release of the drug. Physical parameters and assay were found to be within the acceptable range as prescribed in USP 36 / NF 31. In vitro dissolution studies of each formulation were performed in distilled water, USP dissolution medium, HCl buffer solution of pH 1.2, phosphate buffer solutions of pH 4.5 and 6.8 to observe the drug release. The formulations F3, F4, M4 were selected for film coating on the basis of better drug release profile, to protect the drug from chemical degradation through hydrolysis. Film coated formulation F3, F4 and M4 showed a remarkable in vitro release of the drug (72.88±0.43 to 92.67±0.71%) within 30min of observation in all dissolution media and further evaluated by model independent and model dependent approaches. The drug release was found to be best fit to Weibull model as highest r2adjusted (0.924-0.998) and lowest AIC (18.416-54.710) values were obtained in all dissolution media. R Gui® applied for stability studies of F3 and F4 formulations, showing shelf lives of 28 & 27months at ambient and 33 months at accelerated temperatures. Formulation F4 was chosen as best formulation on the basis of physical properties, highest dissolution rate and stability studies.