Formulation development and optimization studies of mouth dissolving tablets of tizanidine HCl.

The purpose of this research was the development and optimization of mouth dissolving tablets (MDT) of Tizanidine hydrochloride using superdisintegrant. MDTs of Tizanidine (4mg) were manufactured by direct compression method. Formulations comprised of Tizanidine and excipients including croscarmellose sodium, Avicel PH 102, aspartame, orange flavor and magnesium stearate. Blends of powder were assessed for flow characterization and then compressed by direct compression. During post compression stage, a detail evaluation of tablets with respect to weight variation, hardness, thickness, disintegration time, wetting time, friability, drug content analysis, content uniformity, palatability and dissolution studies was carried out. All the formulations complied with the pharmacopeial requirements of weight, disintegration time and assay. Amongst the trial formulations F4 with concentration of croscarmellose sodium i.e. 5% was proved as best optimized due to satisfactory quality attributes such as least disintegration time and sufficient hardness. Hence, it was concluded that manufacturing of mouth dissolving tablets by addition of superdisintegrant is beneficial for treating patients with dysphagia.

Methylphenidate increases the urinary excretion of vanillylmandelic acid in rats that is attenuated by buspirone co-administration.

Methylphenidate is a psychostimulant used for the treatment of (ADHD) attention deficit hyperactivity syndrome in children and adults. After chronic administration it is known to produce behavioral disorders including anxiety. Previous studies demonstrated that co-administration of buspirone can reduce behavioral and cognitive adverse effects produced by methylphenidate. The aim of the present study is to measure the levels vanillylmandelic acid (VMA) excretion in urine following prolong administration of methylphenidate, buspirone and their combination. Samples of urine for the estimation of the urinary VMA excretion were collected from treated and control male Wistar rats. We found significant (P<0.01) raised urinary VMA excretion in methylphenidate group however significant (P<0.01) reduction in VMA levels were seen after buspirone co-administration. Excretion of VMA in urine would allow the monitoring of sympatho-adrenomedullary system activity. This study could be helpful to increase the clinical use of methylphenidate in the treatment of different disoders.

High performance liquid chromatographic method validation for determination of rosuvastatin calcium in tablet dosage forms.

A precise, sensitive and quick High Performance Liquid Chromatographic (HPLC) method for the determination of rosuvastatin calcium in bulk and tablet dosage forms has been validated. The chromatographic scheme involved: Sil-20A auto sampler, LC-20A pump, SPD-20A UV/visible detector with separation attained by C18 column at 40ºC temperature through a mobile phase of acetonitrile and buffer (50:50) at a flow rate of 1.0ml/min. The method is precise (%RSD for intra-day and inter-day extended between 1.06-1.54% and 0.103-1.78%) and linear (r2=0.9997). Limit of detection and quantification (LOD & LOQ) of the adopted method were 0.78 and 1.56µg/ml. The proposed HPLC method was established to be sensitive, precise and swift that can be proficiently adopted in quality control/quality assurance laboratories for predictable investigation of the bulk and oral solid dosage forms of rosuvastatin calcium.

Development and evaluation of immediate release diclofenac sodium suppositories.

The objective of present study was to develop and evaluate polyethylene glycol (PEG) based diclofenac sodium suppositories. This study used water soluble PEG bases (1000, 4000 and 6000) in different combinations to formulate suppositories, which were further subjected for their physicochemical properties evaluation such as weight variation, average melting point, content uniformity and disintegration. Dissolution test was used to perform the in vitro release rate studies of the suppositories. The suppository (P3) containing PEG-6000 (50%) and PEG-4000 (50%) exhibited rapid in vitro release rate of diclofenac sodium. Moreover, homogeneous distribution of diclofenac sodium is found in all six formulations. The in vitro release patterns of diclofenac sodium from the marketed Voltral suppository (100mg) and formulated suppositories were also compared and found in standard limits.

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.

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.

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.

Chromatographic method development and validation for the determination of valsartan in biological fluid.

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 (5µm, 4.6mm × 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 8µg/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.

MRSA: Prevalence and susceptibility pattern in health care setups of Karachi.

This assessment aims to determine the prevalence of methicillin resistance and multidrug resistance (MDR) among the clinical isolates of Staphylococcus aureus and antimicrobial susceptibility profile of methicillin resistant Staphylococcus aureus (MRSA) to the frequently prescribed antibiotics in Karachi. Isolates of MRSA, recovered from various clinical samples were included in this prospective, cross-sectional study from Jan 2015 to June 2017. Agar diffusion method was employed according to the protocols of Clinical Laboratory Standards Institute. Out of total 346 S. aureus strains, the frequency rate of MRSA was 52% (n = 180). MRSA infection was found higher among the age group 21-30 years i.e. 30% (n=54), followed by 20% (n=36) in 31-40 years. Frequency of MRSA percentage in male and female was and 70% and 30% respectively. MRSA was more frequently observed in blood 20% (n=36). MRSA showed high resistance (100%) to Oxacillin and Cefoxitin while 25% Vancomycin resistant S. aureus (VRSA) isolates and 25% Teicoplanin resistance were also reported. MRSA exhibited 16% resistance to Minocycline. It was concluded that MRSA pose a challenging threat to public health in Karachi. In addition, MDR should be periodically checked to avoid treatment failure.