Quality-by-design based development of fast dispersible nimodipine tablets: Formulation attributes and release kinetic assessment.

In the present study fast dispersible nimodipine tablets were developed by direct compression method using quality by design (QbD) approach as per the central composite design by selecting avicel PH 102 (X1) and crospovidone (X2) as independent variables while % friability (R1), disintegration (R2) and hardness (R3) as output variables. Powder blends were assessed for flow characterization. At post compressional stage, several quality assessments were carried out. Particles morphology was observed using scanning electron microscopy (SEM). The stability study on the drug and optimized formulation were determined using thermal gravimetric analysis (TGA) and differential thermal analysis (DTA). RSM plots expressed the interaction of avicel PH 102 and crospovidone to determine the adequate quantities of excipients for the optimized formulation. Polynomial equations were used to validate the experimental design. The optimized formulations were evaluated for friability, disintegration and hardness. Results indicated that formulation (F4) containing avicel PH 102 (35%) and crospovidone (5%) was selected as best optimized formulation having friability 0.59%, disintegration 9 sec, % dissolution 95.703% and hardness 4.14 kg. Results of kinetics models indicated that all the developed formulations followed weibull model.

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.

Drug utilization evaluation of Piperacillin/Tazobactam: A prospective and cross sectional investigation in tertiary care setup.

Drug utilization evaluation (DUE) is an arrangement of continuous, orderly, criteria-based assessment of medication utilizes to guarantee that medicines are utilized suitably. In the event that treatment is regarded to be improper, provider and patient intervention may be important to optimize therapeutic efficacy. In the present study drug utilization evaluation of Piperacillin/Tazobactam was carried out in prospective manner. A well structured data collection form was constructed to collect the related information regarding demographic, clinical use, indication, culture sensitivity criteria, outcomes of therapy, renal impairment cases of dose adjustments and appropriate use. Results of chi square indicated insignificant relationship between gender and as p value was found to be p=0.446 and 0.111 for use of drug alone and in combination. Similarly insignificant relationship between gender and use of drug in combination with other antibiotics as p value was found to be p=0.111. It was found that from 61-70 years (Therapeutic Effectiveness; n=12, 9.37%), (Therapeutic Failure; n=10, 45.45%) and mortality (n=1, 50%) were quite higher. The prescription pattern was in accordance with standard guidelines. Study indicated need to elevate prescribers to pursue generic prescribing and rationally utilize antibiotics to avert advancement of resistance at the level of hospital and community. These sorts of studies are valuable for acquiring data about medication utilize designs and for recognizing inconceivable expense of medicines.

Prevalence of mecA: Genotyping screening of community acquired-MRSA isolates in Karachi, Pakistan.

Among resistant nosocomial and community pathogens, MRSA has become the most serious pathogen, causing life threatening infections worldwide. In S.aureus, quick and exact recognition of methicillin (cefoxitin) resistance has become essential. The benchmark for MRSA identification among S.aureus is the detection of the mecA gene that causes the expression of protein (PBP2a) culpable for classic ß-lactam resistance. However, the utter reliance on amplification of mecA gene as a hallmark in confirmation of methicillin (cefoxitin) resistant S. aureus is the matter of distrust by some investigators. The current investigation designed to analyse the prevalence of mecA gene among phenotypically positive MRSA isolates using molecular method and to correlate its prevalence to conventional techniques. Furthermore, antimicrobial sensitivity of mecA positive staphylococci was determined by Kirby Baeuer method. For this purpose, 201 clinical staphylococcal specimens were recovered from various diagnostic laboratories in Karachi City, Pakistan. Phenotypic existence of methicillin resistance in S. aureus was observed to be 51.7%. In contrast, when organisms were subjected for amplification of mecA gene by PCR, mecA positive isolates were 36/104 (35%) MRSA isolates. Current work raise question towards the usefulness of molecular identification of mecA gene in confirmation of methicillin resistance without correlating with conventional methods. Therefore, it is essential to consider the other possible resistance mechanisms for ß-lactams that may interact with mecA gene in the development of methicillin resistance mechanism in Staphylococcus.

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.

Staphylococcal resistance against five groups of life saving antibiotics in the year 2003-2005.

In the year 2003 to 2005 a prospective study was conducted to find out the predominance of Staphylococcus (Staphylococcus aureus) resistance pattern in opposition to five life saving antibiotics as these are the sole agents to treat critically ill patients in hospitals. During the period of two years almost 2500 samples of bacterial culture were taken from different pathological laboratories and hospitals in Karachi. Among these 1500 were Gram positive cocci and 1000 samples were identified as Staphylococcus aureus. Life saving antibiotics were taken from five different groups and by mean of disk diffusion technique antibiogram of Staphylococcus aureus against these antibiotic were determined. During the course of study imipenem showed 11%, amikacin exhibited 58%, cefipime showed 31%, vancomycin and piperacillin/tazobactam displayed 24% resistance against Staphylococcus aureus. Imipenem was found to be most effective against Staphylococcus aureus.Resistance to other antibiotics developed quickly in Staphylococcus aureus collected from clinical areas where these antimicrobial agents are extensively used.

Comparative study on resistant pattern of clinical isolates against levofloxacin and cefepime.

The aim of this study is to evaluate the susceptibility and resistance pattern of clinical isolates causing different types of infections and to compare the efficacy of antibiotics namely levofloxacin and cefepime. The in-vitro antibacterial activity and resistance patterns of these two well known antibiotics were studied and compared using disk diffusion method. For this, one hundred clinical isolates comprising of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa were collected from different local pathological laboratories and hospitals. Escherichia coli (17.95% against cefepime and 30.77% against levofloxacin), Staphylococcus aureus (30% against cefepime and 46.66% against levofloxacin) and Pseudomonas aeruginosa (23.53% against cefepime and 35.29% against levofloxacin) were found resistant against the studied antibiotics which show that cefepime is more effective than levofloxacin. In case of Klebsiella pneumoniae, resistance was 42.85% against cefepime and 35.71% against levofloxacin thereby showing that levofloxacin is more effective than cefepime. Concluded that the clinical isolates collected were susceptible to both the antibiotics but the microbial resistance against these antibiotics is increasing in our population which is alarming. Therefore, it is recommended the physicians may prescribe these antibiotics unless no other substitute is available in clinical practice.

Anti-inflammatory and analgesic activities of ethanolic extract of Sphaeranthus indicus Linn.

The aim of the present study was to evaluate the intensity of the anti-inflammatory and analgesic activities of Sphaeranthus indicus on albino mice and rat of either sex. The flowers of S. indicus are an important herb used in folk eastern medicines. In this study, the ethanolic extract of S. indicus in doses of 300 and 500 mg/kg was used. Anti-inflammatory activity was evaluated by measuring the mean decrease in hind paw volume after the sub planter injection of carrageenan. The analgesic activity was tested against acetic acid induced writhing response using albino rats. Result of the study shows that at the end of one hour the inhibition of paw edema was 42.66 and 50.5% respectively and the percentage of protection from writhing was 62.79 and 68.21 respectively. S. indicus possesses several important pharmaceutical and pharmacological properties. The current study describes that flower of S. indicus has significant anti-inflammatory and analgesic properties. Conclusion of the study is that this herbal medicine can be used as an alternative therapy for the treatment of minor to moderate types of inflammation and as a painkiller.