Formulation development of directly compressible mebevarine tablets using superdisintegrant: A way to investigate quality atributes, in vitro release kinetics and stability profile.

In order for preparing a solid oral dosage form, tablet quality is of significant concern. Compressibility behavior of different powders and mixtures of formulations and release pattern of any tablets are characteristic measures to define prerequisite quality attributes of any compressed formulations. There are basically two major methods that can be adopted for the preparation of tablets including granulation and direct compression. Later process offer fewer processing steps and agreeable release profile with acceptable quality parameters and hence preferred over granulation method. In this investigation Mebeverine hydrochloride an anti-muscarinic drug is studied for compression and release behavior using various concentrations of filler binders and disintegrants via rotatable central composite design (CCRD) option of design expert (software). Nine formulations were developed from F1 to F9 with Crospovidone (superdisintegrant) as (X1) (-α=1.17% to ± α=6.83%) and microcrystalline cellulose (Avicel 102, Filler/binder) as X2 (-α = 29.82% to ± α = 65.18%). Disintegration Time (DT) as (R1) and Hardness in (kg) as (R2) were determined as two dependent response variables. The performance of powder blends and formulations was analyzed by micromeritic and physico-chemical and assessments. Dissolution comparisons were statistically analyzed by ANOVA and model dependent and in-dependent methods. Best fit model was found to be Hixon-crowell's model (r2 = 0.995) followed by Weibull's model (r2 = 0.985). The Trial formulations F2, F4, F6 and F8 were also studied on accelerated conditions (40±5ºC 75%±5% RH) for stability tests and validity of the formulations in months were also determined between 35-39 months.

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.

Effect of Methylphenidate and buspirone-methylphenidate co-administration on biochemical and hematological parameters in rats: Implications for safe and confrontational use.

Methylphenidate (MPH) is a psychostimulant, beneficial in attention deficit hyperactivity disorder (ADHD). Previously it has been shown that MPH-induced locomotor sensitization could be attenuate by buspirone co administration however the effect of chronic MPH and co-administration of MPH-buspirone on biochemical and hematological parameters are unknown. This study is designed to investigate these parameters after long term administration of MPH, Buspirone and their combination in rats. 40 male Wister rats were divided in to 4 groups, and treated with saline, MPH (2mg/kg/day), Buspirone (10mg/kg/day) and MPH-Buspirone co-administration (2mg/kg/day ±10mg/kg/day; respectively) up to six weeks. Administration of MPH significantly increase blood glucose level in saline treated control rats, however co-administration of MPH-buspirone exhibited less effect on blood glucose levels. Serum creatinine levels significantly decreased in all treated groups as compared to control but highly significant results were seen with combination treatment. Co-administration of MPH-buspirone and buspirone treated rats exhibited increased cholesterol and hemoglobin values. All treated groups showed increased values of hematocrit, MCV, MCH and MCHC compared to control group. RBCs and WBC's count were decreased in all treated groups. The platelet count rose significantly by Buspirone and MPH-buspirone administration, while MPH showed decreased platelet count. Thus, results suggested that prolong co-administration of MPH-buspirone is safe and effective for ADHD patients by preventing adverse effects not only on behavioral but also on biochemical and hematological parameter.

High prevalence of DR-TB (drug-resistant tuberculosis): An Indicator of public health negligence.

Tuberculosis (TB) is among the 10 most common worldwide causes of mortality. In Pakistan, estimated 510,000 tuberculosis patients had been diagnosed with an occurrence of 276/100,000. As per most recent global TB report 2018, Pakistan is amongst the 30 countries high TB with drug-resistant Mycobacterium tuberculosis particularly MDR (multi-drug resistant strains). A retrospective study had been designed using DR-TB patients' records from January 2013 to the December 2017 year from a public sector hospital in Karachi. Overall 315 drug-resistant tuberculosis patient's data had been incorporated in the study. All data had been analyzed using SPSS version 16 software. Chi-square test had been used to analyze the data with CI (confidence interval) 95% and level of significance 5%. The study result showed that 64.1% MDR patients, 27.9% MTB rifampicin resistance, 4.8% mono-drug resistant , XDR(1.6%), 1% poly-drug resistant and only 0.6% are MDR suspects showing no association of DR-TB with gender (p-value 0.787), age group (p-value 0.757), treatment outcomes (p-value 0.549), year of registration( p-value 0.206), first line treatment history(p-value 0.643) with a 95% confidence interval. The drug resistance TB cases have been periodically rising every year. Early identification is required to reduce the percent mortality and inhibit the disease transmission.

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.

Community onset of CTX-M extended spectrum ß-lactamases among uropathogenic E. coli and K. pneumoniae from Karachi, Pakistan.

Urinary tract infections (UTIs) are major health issue in developing countries like Pakistan, become more complicated with extended spectrum ß-lactamase (ESBL) expression in Escherichia coli and Klebsiella pneumoniae. The ground of this present study was to evaluate the incidence of cefotaxime (CTX-M) gene in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. The clinical isolates from various specimens were collected for one-year duration from January till December 2015. After initial screening (n=352) isolates were examined for phenotypic expression of ESBLs by double disc synergy test. Furthermore, eight-four isolates were analyzed by polymerase chain reaction for identification of Cefotaxime (CTX-M), Temoneira (TEM) and Sulfhdryl variable (SHV) genes. Among eighty-four clinical isolates CTX-M was dominant and found positive in 50 isolates (59.5%) followed by TEM in 35 (41.6%) and SHV in 11 (13%). In uropathogenic E. coli and K. pneumoniae, ESBLs gene was found in 50 and 6 isolates out of 57 and 7 respectively. Among uropathogens CTX-M was most prevalent 78% (39/50) in E. coli followed by K. pneumoniae. In uropathogenic E. coli, CTX-M was found dominant in females. The study concluded that ESBL related uropathogenic E. coli were CTX-M dominant, showed community onsets of UTIs that can be preventive and controlled with modified hygienic practices.

Pharmaceutical quality evaluation of different glimepiride brands marketed in Karachi (Pakistan): In pursuance to global issue of availability and affordability of quality medicines.

Availability of economical quality medicines is always required for chronic disease management. Price differences among multiple brands of a product do not essentially displays low quality for the more affordable brand, however in a few occurrences it appears. Glimepiride, an oral anti-diabetic drug, is produced by several national and multinational industries in Pakistan with considerable cost variation. The study aimed to evaluate the quality and economy of various Glimepiride brands available in Karachi, specifically of public sector hospitals. For this, eight glimepiride brands were collected and analyzed for the pharmaceutical quality using physical parameters, disintegration test, dissolution profile, spectrophotometric assay and content uniformity. Pharmacoeconomic assessment was also carried out such as availability, affordability and price variation. A profound discrepancy was observed among the prices of selected brands. All of the products found to be equivalent to the reference product except G5, the most inexpensive and highest consumed product of a public sector hospital. Study concludes that products with higher quality and lesser price can be used as a substitute to the costly brands while availability of a substandard product looks for consideration of pertinent authorities to assure the distribution of quality 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.

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.