Exploring the antimicrobial and cytotoxic potential of novel chloroquine analogues.

Aim: To synthesize novel chloroquine analogues and evaluate them for antimicrobial and cytotoxic potential. Methods: Novel analogues were synthesized from chloroquine by nucleophilic substitution reaction at the 4-amino position. Results: Analogue CS1 showed maximum antimicrobial potential (30.3 ± 0.15 mm zone) against Pseudomonas aeruginosa and produced a 19.2 ± 0.21 mm zone against Candida albicans, while CS0 produced no zone at the same concentration. Analogue CS9 has excellent cytotoxic potential (HeLa cell line), showing 100% inhibition (IC50 = 8.9 ± 1.2 µg/ml), compared with CS0 (61.9% inhibition at 30 µg/ml). Conclusion: These synthesized chloroquine analogues have excellent activity against different microbial strains and cervical cancer cell lines (HeLa) compared with their parent molecule.

[Box: see text].

Thyroid cancer risk factors and Pakistani University students' awareness towards its preventive practice.

OBJECTIVES: Thyroid Cancer is one of the rarest cancers but its prevalence has been increasing worldwide for the last couple of decades. METHODS: The data collection tool was designed to assess knowledge, awareness, perception, and attitude towards preventive practices of thyroid cancer in Pakistani university students. The data were collected over a duration of six months and a total number of 3722 students participated. RESULTS: The knowledge of risk factors of thyroid cancer was an important parameter of this study. The students who knew all the early signs of thyroid cancer were 28.7%. In this study, the independent variables such as age, gender, demographic location, and financial status were found to be highly significant with knowledge, attitude towards warning signs of cancer, and the perception of students about developing thyroid cancer. CONCLUSIONS: The participants were found to have poor knowledge about early signs of thyroid cancer. The study participants perception, behavior, and attitude towards preventive practices of thyroid cancer were found inadequate and appropriate measures on a National level should be taken to enhance the knowledge about preventive practices of thyroid cancer. Increasing knowledge and awareness shall help decrease the overall morbidity and mortality linked with thyroid carcinomas and thyroid diseases.

Enhancing the Antibacterial Activity of Erythromycin with Titanium Dioxide Nanoparticles against MRSA.

BACKGROUND: Staphylococcus aureus (S. aureus) is the most common infectious agent in the community and hospitals. Infections with S. aureus are now becoming difficult to be treated by using conventional antibiotics due to its emerging methicillin-resistant S. aureus (MRSA) strain. OBJECTIVE: In the present study, MRSA was isolated from clinical samples and evaluated for resistance against different antibiotics, TiO2 nanoparticles, and their combinations. METHODS: Clinical samples were collected from Ayub Medical Complex (AMC), Abbottabad, Pakistan, and identified by different biochemical tests and polymerase chain reactions (PCR). Kirby-Bauer disk diffusion method was performed to evaluate antimicrobial susceptibility. Minimum Inhibitory Concentration (MIC) of ampicillin, ciprofloxacin, erythromycin, and vancomycin was found out by agar dilution method while the broth dilution method was used for the MIC of TiO2 nanoparticles and their combinations with erythromycin. RESULTS: All 13/100 (13%) MRSA were successfully identified. All isolates were susceptible to quinupristin/ dalfopristin, teicoplanin, and vancomycin, while the highest resistance was seen with erythromycin, penicillin, and tetracycline. MIC showed high resistance against ampicillin (0.25-512 mg/L) and erythromycin (0.25-1024 mg/L). CONCLUSION: The MIC value of 2 mM TiO2 nanoparticles was found to be the most effective concentration after 12 h of incubation, while the combination of erythromycin with 3 mM TiO2 nanoparticles was found to be more potent which significantly lowered down the MIC of erythromycin to 2-16 mg/L.

Finasteride Topical Delivery Systems for Androgenetic Alopecia.

Androgenetic alopecia, generally recognized as male pattern baldness, is a gradually developing medical and physiological change, which is manifested by continuous hair-loss from scalp. Finasteride (4-aza-3-oxosteroid) is a potent anti-baldness compound that selectively and competitively inhibits the 5α-reductase isoenzymes. Prolonged oral use of finasteride leads to the emergence of sexual disorders including decrease in libido, gynecomastia, erectile dysfunction, ejaculation disorder, orgasm disorders and mood disturbances. Since, hair follicles widely home in 5α-reductase, topical formulations of finasteride in comparison to its oral formulations are expected to potentially reduce its systemic adverse effects. The analysis of literature has revealed some delivery systems developed for the enhanced and localized penetration of finasteride into the skin. These finasteride delivery systems include polymersomes, vesicular nanocarriers, vesicular ethosomal carriers, liposomes and niosomes, liquid crystalline nanoparticles, topical solutions and gels. The aim of this review article is to briefly amass all literature on topical delivery of finasteride to elaborate best dosage form, i.e. formulation having maximum permeation rate. This study will serve as a future perspective regarding topical delivery of finasteride. The literature analysis has exhibited that most of the previous investigators have used propylene glycol in their finasteride-loaded topical formulations, while poloxamer P407, monoolein, transcutol P and choline was used in few formulations. Moreover, among all drug delivery systems, finasteride liposomal gel system consisting of 2% methyl cellulose and gel system containing poloxamer P407 exhibited the highest flux with a value of 28.4 ± 1.3 µg/cm2h and 23.1 ± 1.4 µg/cm2h, respectively. Several topical drug delivery techniques such as topical microneedles, aerosol foams, nanoemulsions, microsponges, and emulsifier free formulations, fullerenes, ointments, pastes, creams, gel and lotions are still to be worthy regarding finasteride topical delivery in future.

FORMULATION, EVALUATION AND IN VITRO DISSOLUTION PERFORMANCE OF ENALAPRIL MALEATE SUSTAINED RELEASE MATRICES: EFFECT OF POLYMER COMPOSITION AND VISCOSITY GRADE.

The present study aimed at developing the sustained release matrix tablets of enalapril maleate and evaluating the effect of polymer concentration and viscosity grade on drug release. The sustained release enalapril maleate tablets were successfully formulated by direct compression method using nonionic cellulose ethers HPMC K15, HPMC K100 and HPC polymers either alone or in combination. In-vitio drug release study was carried out in phosphate buffer (pH 6.8) for a period of 24 h following USP dissolution apparatus II i.e., paddle apparatus. Model dependent approaches like zero-order, first order, Higuchi's model and Korsmeyer-Peppas model were used to assess drug release from various formulations. All the three polymers alone or in combination sustained the drug release. The drug release characteristics from HPMC and HPC polymer followed zero order release kinetics except for 45% concentration of all polymers alone or in combination where by the drug release followed Higuchi's model. In all cases, the drug release mechanism was both diffusion as well as erosion.

Phospholipases A2: enzymatic assay for snake venom (Naja naja karachiensis) with their neutralization by medicinal plants of Pakistan.

Phospholipases A2 (PLA2) are the most lethal and noxious component of Naja naja karachiensis venom. They are engaged to induce severe toxicities after their penetration in victims. Present study was designed to highlight hydrolytic actions of PLA. in an egg yolk mixture and to encounter their deleterious effects via medicinal plants of Pakistan. PLA2 were found to produce free fatty acids in a dose dependent manner. Venom at concentration of 0.1 mg was found to liberate 26.6 pmoles of fatty acids with a decline in pH1 of 0.2 owing to the presence of PLA2 (133 Unit/mg). When quantity of venom was increased up to 8 mg, it caused to release 133 pmoles of free fatty acids with a decrease in 1.0 pH due to abundance in PLA, (665 Unit/mg). The rest of other doses of venom (0.3-4.0 mg) was found to liberate fatty acids between these two upper and lower limits. Twenty eight medicinal plants (0.1-0.6 mg) were tried to abort PLA, hydrolytic action, however, all were found useful (50-100%) against PLA,. Bauhinia variegate L., Citrus limon (L.). Burm.f. Enicostemnma hyssopifolium (Willd.) Verdoorn, Ocimum sanctum. Psoralea corylifolia L. and Stenolobium stans (L.) D. Don were found excellent in switching off 100% phospholipases A, at their lowest concentration (0.1 mg). Three plants extract were found useful only at lower concentration (0.1 mg), however, their higher doses were seemed to aggravate venom response. Eight medicinal plants failed to neutralize PLA, rather their higher doses were found effective. Standard antidote and rest of other plants extract were able to show maximum of 50% efficiencies. Therefore, it is necessary to identify and isolate bioactive constituent(s) from above cited six medicinal plants to eradicate the problem of snake bite in the future.

Evaluation of self-medication amongst university students in Abbottabad, Pakistan; prevalence, attitude and causes.

Self-medication is a serious issue in most parts of the world. This study aims to evaluate self-medication among university students of Abbottabad, Pakistan. This cross-sectional survey study was carried out in COMSATS Institute of Information Technology, Abbottabad during December 1 - December 31,2011. A sample of 275 students was selected for the study using convenience method of sampling. Data were managed and analyzed via SPSS version 16.0. Inferences were drawn using Z-test Out of 268 respondents (male = 61.6%, female = 38.6%), 138 were non-health professional students whereas 130 were health professional students. The prevalence of self-medication was 95.5%. Most common factor (45.7%) responsible for self-medication was "low severity of disease". Most common symptom (50.8%) that caused self-medication and stocking of medicines was "storage of medicines for multi purposes". Some respondents (22.7%) got addicted due to self-medication. Most of the students trust in allopathic medicines system. High prevalence of self-medication can be controlled through regulatory authorities, mass education and availability of health facilities.

Pharmacokinetic study of hydroxypropylmethylcellulose microparticles loaded with cimetidine.

OBJECTIVES: The objective of this study was to assess the pharmacokinetic behavior of floating hydroxypropylmethylcellulose microparticles loaded with cimetidine (FMC) prepared using the non-solvent addition coacervation technique. MATERIAL AND METHODS: Based on the physico-chemical characteristics of three formulations (FMC1, FMC2 and FMC3), FMC2 having a 1:3 ratio of cimetidine:HPMC was found optimum. For in vivo analysis, a new HPLC analytical method was developed and validated. The optimized formulations were subjected to in vivo studies to calculate the various pharmacokinetic parameters for developed optimized microparticulate formulation FMC3. The developed floating microparticles of cimetidine were further evaluated by in vivo experimentation. RESULTS: The bioavailability parameters were found as: Cmax 1508.79 ± 37.95 ng/ml, Tmax 3.67 ± 0.17 h and AUC 14366.19 ± 377.64 ng h /mL. CONCLUSIONS: For prolonged drug release in the stomach, developed floating microparticles of cimetidine (FMC3) may be used, thereby improving the bioavailability and patient compliance.

Mixed methodology approach in pharmacy practice research.

Healthcare providers play a major role in attending to all domains of health in a population. In terms of modem healthcare delivery, better health outcomes for population can be achieved by engaging multi-disciplinary expertise. In the last decade, pharmacy profession had transformed tremendously in terms of health and pharmaceutical service provision to both patients and general population. Within this practice transformation, pharmacists, especially those in developed countries, now occupy a respectable position within the healthcare system. In contrast, services and expertise offered by pharmacists in developing countries are still underutilized, and their role as healthcare professionals is not deemed to be important either by the community or by other healthcare providers, especially doctors and nurses. In order to explore the current perspectives regarding the role of pharmacists in the context of a developing country, a systematic research is needed. Mixed methodology research should be used for evidence generation. The philosophy of mixed method research came up decades ago. This approach is widely recommended for social and human sciences research. In recent existence, many researchers have begun to recommend mixed methods research as a separate methodology or design. Many factors have brought into the evolution of mixed methods research. A combination of both forms of data can provide the most complete analysis of the issues related to the pharmacy practice research. Numbers in quantitative and words in qualitative can be enclosed together to give the better understanding of research questions. Both forms of data are necessary for pharmacy practice research especially in case of developing countries where there is a need to generate the evidence for future health policy.

A novel granulation non-solvent addition method containing hydrophilic and lipophilic drugs.

Atenolol and simvastatin were granulated in combination by non-solvent addition coacervation method to treat hypertension orally. Dissolution test was performed in water containing 0.5% sodium dodecyl sulfate at 37 0.05 degrees C. FTIR spectrometry, X-ray diffractometry and thermal analysis confirmed the absence of any chemical interaction between polymer and the entrapped drugs. The granules size was about 280-619 µm. Scanning electron microscopy reported irregular morphology of granules. The entrapment efficiency was approximately 90% for atenolol and 70% for simvastatin. A controlled release behavior of both drugs but a burst release phenomenon of simvastatin from the formulations were observed. In conclusion, granules loaded with a hydrophilic and a lipophilic drug were successfully prepared.

Design, development and in-vitro evaluation of metoprolol tartrate tablets containing xanthan-tragacanth.

The present study was undertaken to develop oral sustained release tablets of metoprolol tartrate using natural hydrophilic matrix formers (xanthan gum and tragacanth). Sustained release matrix tablets of metoprolol tartrate were prepared by using different ratios of drug, xanthan gum and tragacanth. Microcrystalline cellulose (MCC) was used as diluent. The polymer was incorporated into a matrix system using direct compression technique. All the lubricated formulations were compressed using concave punches in compression machine. Compressed tablets were evaluated for diameter, hardness, friability, weight variation and in vitro dissolution using USP dissolution apparatus-II. Different formulations were evaluated with respect to dissolution profile in 900 mL phosphate buffer (pH 6.8), 0.1 M HCl solution and distilled water for 12 h at 37 degrees C. Increasing the amount of polymer (xanthan gum) in the formulation led to slow release of drug and decreasing the amount of polymer gave enhanced release of metoprolol tartrate. The kinetic treatment showed the best fitted different mathematical models (Zero order, First order, Higuchi's and Hixson-Crowell). Most of the solid matrix formulations followed Higuchi or zero order kinetics. The formulations F1, F2, F3 and F7, F8, F9 showed maximum linearity while the formulations F4, F5, F6 were not of linear behavior. The results showed that the formulation F9 containing 30% xanthan gum and 10% gum tragacanth is the most similar to that of the reference marketed preparation.

Formulation of two-drug controlled release non-biodegradable microparticles for potential treatment of muscles pain and spasm and their simultaneous spectrophotometeric estimation.

The objective of this study was to formulate stable and controlled release microparticles for simultaneous delivery and UV spectrophotometric detection in combined dosage of an non-steroidal anti-inflammatory drug (NSAID) (nimesulide, NMS) and a spasmolytic agent (tizanidine, TZN) to maintain plasma concentration that may increase patients compliance, improved therapeutic efficacy, The aim was also to reduce severity of upper GI side effects of NMS because of alteration in delivery pattern via slow release of drug from microparticles and to increase the benefits of spasticity and disability for spastic patients by administering TZN in a modified release formulation as these two drugs are often prescribed in combination for the management of pain associated with muscles spasm. Ethyl cellulose was used as a retardant polymer. Drug-polymer and drug-drug compatibility study were conducted by different analytical tests. Microparticles were prepared by coacervation thermal change method. The prepared microparticles were characterized for their micromeritics and drug loading. The prepared microparticles were light yellow, free flowing and spherical in shape. The drug-loaded microparticles showed 87% and 91% entrapment efficiency of NMS and TZN, respectively, and release was extended up to 10 h. The infrared spectra, differential scanning calorimetry thermograms and XRD spectra showed the stable character of both the drugs in the drug-loaded microparticles. The in vitro release study of microparticles was performed in phosphate buffer pH 6.8. Linearity was observed in the concentration range of 5.0-30.0 microg/mL of NMS and 0.5-3.0 microg/mL of TZN. The microparticles have a potential for the prolongation and simultaneous delivery of the NIM and TIZ. The proposed UV method for simultaneous detection can be used for routine analysis of combined dosage form.