Cosmos caudatus (ulam raja) contains high mineral content and possesses high antioxidant activity which may be beneficial in bone disorder such as postmenopausal osteoporosis. The effects of C. caudatus on bone metabolism biomarkers in ovariectomized rats were studied. 48 Sprague-Dawley rats aged three months were divided into 6 groups. One group of rats was sham-operated while the remaining rats were ovariectomized. The ovariectomized rats were further divided into 5 groups: the control, three groups force-fed with C. caudatus at the doses of 100mg/kg, 200mg/kg or 300mg/kg and another group supplemented with calcium 1% ad libitum. Treatments were given 6 days per week for a period of eight weeks. Blood samples were collected twice; before and after treatment. Parameters measured were bone resorbing cytokine; interleukin-1 and the bone biomarkers; osteocalcin and pyridinoline. Serum IL-1 and pyridinoline levels were significantly increased in ovariectomized rats. Supplementation of C. caudatus was able to prevent the increase of IL-1 and pyridinoline in ovariectomized rats. Besides that, C. caudatus showed the same effect as calcium 1% on biochemical parameters of bone metabolism in ovariectomized rats. In conclusion, Cosmos caudatus was as effective as calcium in preventing the increase in bone resorption in ovariectomized rats.
The present work investigates the formulation and biopharmaceutical estimation of gastric floating drug delivery system (GFDDS) of propranolol HCl using semi-synthetic polymer carboxymethyl ethyl cellulose (CMEC) and a synthetic polymer polyethylene oxide (PEO). A central composite design was applied for optimization of polymer quantity (CMEC or PEO) and sodium bicarbonate concentration as independent variables. The dependent variables evaluated were: % of drug release at 1 hr (D1hr), % drug release at 3 hr (D3hr) and time taken for 95% of drug release (t95). Numerical optimization and graphical optimization were conducted to optimize the response variables. All observed responses of statistically optimized formulations were in high treaty with predicted values. Accelerated stability studies were conducted on the optimized formulations at 40 ± 2°C/75% ± 5% RH and confirm that formulations were stable. Optimized formulations were evaluated for in vivo buoyancy characterization in human volunteers and were found buoyant in gastric fluid. Gastric residence time was enhanced in the fed but not the fasted state. The optimized formulations and marketed formulation were administered to healthy human volunteers and evaluated for pharmacokinetic parameters. Mean residence time (MRT) was prolonged and AUC levels were increased for both optimized floating tablets when compared with marketed product. High relative bioavailability obtained with optimized gastric floating tablets compared to commercial formulation, indicated the improvement of bioavailability.
Cyathula prostrata (Linn) Blume herbs are commonly used for the treatment of inflammatory and pain in Nigeria. The objective of the present study was to assess the antitumor and antioxidant activity of Cyathula prostrata (Linn) Blume in mice model. The treatment of Dalton's lymphoma ascites cells induced tumor by the methanolic extract of Cyathula prostrata was determined at concentration of 100 mg/ kg body weight given orally for 11 days, antitumor activity was assessed by monitoring the mean survival time, body weight, effect on hematological parameters, antioxidant enzyme levels and histopathological evidence. The results showed that the methanolic extract of Cyathula prostrata increased the survival period of animals, decreased the body weight and also altered many hematological markers and also restored the antioxidant enzymes when compared to the mice of the DLA control group. These findings indicate that the methanolic extract of C. prostrata has anti-tumor activity by preventing the lipid peroxidation and thereby promoting the antioxidant systems in Dalton's lymphoma ascites induced mice. So, these extract could be a natural anticancer agent for human health.
This study is an observational cross-sectional study aimed to examine the possible demographic and social characteristics of patients enrolled at the Methadone Maintenance Therapy Adherence Clinic (MMTAC) in Malaysia. Medical records from year 2009 - 2011 were Reviewed. Demographic, social characteristics and laboratory examinations such as age, gender, race, clinic attendances and urine analysis were recorded. Subjects were selected by means of convenient sampling but based on the specified inclusion and exclusion criteria. Data were analyzed by either Chi-square test, Fisher's exact test Mann-Whitney U-test, with the limit of significance was set at p < 0.05. Demographically, this study found that the ratio of Malays, Chinese and Indian enrolled to the MMTAC program is similar to the distribution of races in Malaysia. Their starting age for drug use was between 14-35 years and the age to enrolment between 30-58 years. Socially, many are unemployed, lowly educated and married. Most are drug users with a high percentage of HCV accompanied with impaired liver function. Retention rate was 87% but illicit drug use was at 57.50%. However, percentage of employment increased significantly after therapy. The study managed to identify several demographical and social distributions of patients attending the MMTAC. Although attendance rate was high, many were on illicit drug use. Nevertheless, employment rate improved significantly.
Study site: government methadone clinic in Klang, Selangor, Malaysia
Out-of-pocket (OOP) payments may burden Methadone Maintenance Clinic patients. Since treatment is fully subsidized by the government, financial constraint might lead to patients being made to pay or be given incentive for inconvenience of therapy. This study thus evaluates the characteristic and commitment of methadone therapy patient's in terms of OOP cost, Willingness-To-Pay (WTP) and Willingness-To-Accept (WTA) concept. This survey utilizes the questionnaire by Boris ova & Goodman (2003) on the OOP, WTP and WTA. The forty adult patient's selected medical records from year 2009-2011 were from an urban government methadone clinic. Subject's selection was by convenient sampling based on the predetermined criteria. Most were male (95%) and Malay (60%) was the predominant group. Patients were group into three income groups; ≤ RM1000, ≥ RM1000 -≤ RM2000 and ≥ RM3000. The average OOP cost per month was RM391.30 (s.d RM337.50), which is about 35% of employed patient's monthly income. The wide variation could be attributed by high inter-individual and significant differences between patients in terms of transport, times taken to clinic, cost per trip and weekly household income (p=<0.05). Patients with income of less than RM1000 showed the highest tendency to pay for treatment, asked for the least money for inconvenience and many are unwilling to accept any payments. These findings showed that WTP and WTA is less of a concern for patients in the low-income group. To conclude, OOP payment is not a treatment barrier for most of the urban MMT patients.
Date Fruits are consumed in Arab areas for a long time as a part of essential diet. Phoenix dactylifera belongs to family Arecaceae and its leaves, barks, pits, fruits and pollens have anticancer, antioxidant, hepatoprotective, antidiabetic, antihypertensive, antiulcertavie, anti-inflammatory, antiproliferative, antimutagenic, antidiarheal, antibacterial, antifungal and antiviral potential. Besides these, Dates also increase level of estrogen, testosterone, RBCs, Hb, PCV, reticulocytes and platelet counts. It can also cure lead induced heamotoxicity, side effects of methylprednisolon, male and female infertility. It has also cerebroprotective, neuroprotective and haemopoietic activity. Phoenix dactylifera can be used for number of complications if further evaluated and isolated. The present paper is an overview of pharmacological properties of Phoenix dactylifera reported in literature.
Structure-activity relationships of eleven xanthones were comparatively predicted for four cancer cell lines after the compounds were subjected to antiproliferative assay against B-lymphocyte cells (Raji), colon carcinoma cells (LS174T), human neuroblastoma cells (IMR-32) and skin carcinoma cells (SK-MEL-28). The eleven chemical constituents were obtained naturally from the stem bark of Calophyllum inophyllum and Calophyllum soulattri. Inophinnin (1) and inophinone (2) were isolated from Calophyllum inophyllum while soulattrin (3) and phylattrin (4) were found from Calophyllum soulattri. The other xanthones were from both Calophyllum sp. and they are pyranojacareubin (5), rheediaxanthone A (6), macluraxanthone (7), 4-hydroxyxanthone (8), caloxanthone C (9), brasixanthone B (10) and trapezifolixanthone (11). Compound 3 was found to be the most cytotoxic towards all the cancer cell lines with an IC50 value of 1.25μg/mL while the simplest xanthone, compound 8 was inactive.
Empagliflozin is a selective inhibitor of sodium glucose co-transporter II, given as mono therapy or an add-on treatment to reduce the glycated hemoglobin levels in type 2 diabetes. This work deals with designing, formulating and optimizing empagliflozin (10mg) immediate release (IR) tablets by direct compression technique using different excipients. Through central composite rotatable design (CCRD), total nine formulations (EF1-EF9) were generated by changing the composition of binder avicel PH 102® (X1) and superdisintegrant acdisol⌖ (X2). Formulation runs with in suitable weight range and powder properties were subjected to compression. The influence of interaction of excipients on friability (Y1), hardness (Y2) and disintegration (Y3) were analyzed by fitting the polynomial quadratic model with response surface methodology (RSM). Trials EF2, EF7, EF8 and EF9 exhibited acceptable tablet attributes upon physico-chemical testing. Different dissolution models were applied to observe the in vitro drug release pattern in phosphate buffer of pH 6.8. The cumulative drug release of IR tablet batches followed the Weibull kinetics with regression coefficient (r2) values of 0.983-0.992. Empagliflozin trials were exposed to accelerated storage conditions (40±2°C/ 75±5% RH) for stability testing. Shelf life period of exposed formulations were computed in range of 22 to 25 months. Keeping in view of the results, it is concluded that the employed technique of preparation and optimization are observed to be excellent for developing immediate release empagliflozin (10mg) tablets.
The current investigation is based on efficient method development for the quantification of empagliflozin in raw and pharmaceutical dosage forms, as no pharmacopoeial method for the drug is available so far. The developed analytical method was validated as per ICH guidelines. C18 column with mobile phase (pH 4.8) consisted of 0.1% trifluoroacetic acid solution and acetonitrile (70:30 v/v) was used for drug analysis. The calibration plot showed good linear regression (r2>0.999) over the concentration of 0.025-30 μg mL-1. The LOD and LOQ were found to be 0.020 μg mL-1 and 0.061 μg mL-1, respectively. The percentage recovery was estimated between 98.0 to 100.13%. Accuracy and precision data were found to be less than 2%, indicating the suitability of method for routine analysis in pharmaceutical industries. Moreover, the drug solution was found to be stable in refrigerator and ambient room temperature with mean % accuracy of >98%. Empagliflozin contents were also tested in both the raw API and marketed tablet brands using this newly developed method. The mean assay of raw empagliflozin and tablet brands were ranged from 99.29%±1.12 to 100.95%±1.69 and 97.18%±1.59 to 98.92%±1.00 respectively. Based on these findings, the present investigated approach is suitable for quantification of empagliflozin in raw and pharmaceutical dosage forms.
Falls are a major problem among the elderly and can lead to serious injury. Adults older than 65 years suffer the greatest number of severe falls. This study aims to evaluate the knowledge and perception of medication related falls as well as preferred medication related fall prevention programs in the local population. A cross-sectional survey was conducted among the elderly patients in a tertiary hospital. A total of 86 patients (n=86) were interviewed. Approximately 23.3% (20 patients) of the elderly had a history of falls over the past 6 months. Majority of the elderly considered falls as a major concern (80 patients, 93%) and is preventable (55 patients, 64%). Patients with a medical condition reported a significantly greater number of falls within the past 6 months (p<0.001). Approximately 69% (59 patients) of the elderly were aware of their medication and associated risk of falls. In patients that were unaware of medication associated risk of falls, 81.5% (22 patients) had a potentially inappropriate medication preferred preventive interventions for medication related falls were related to strength and training programs (37 patients, 43%). The knowledge of falls, medication related falls and intervention strategies in the elderly were minimal.
A simple and sensitive stability-indicating HPLC-UV method was developed and validated for the determination of montelukast in the development of chewable tablet formulation. Chromatographic separation was achieved using Atlantis® T3 3µm C18 (4.6mmID X 10cm) analytical column. The mobile phase was consisted of KH2PO4 (0.05mM)-ACN-TEA (450:550:1.33, v/v/v) adjusted to pH 2.0 with orthophosphoric acid. The analysis was run at a flow rate of 1.5 mL/min with detection wavelength at 255nm. Method validation was performed in accordance with ICH guideline. Stress degradation studies, comprising of acid and alkali hydrolysis (1M HCl and 1M NaOH), oxidative degradation (3% H2O2), photo degradation and heat degradation, were performed. The standard calibration curve was linear from 0.0025 - 0.375mg/mL. The LOD and LLOQ were 0.01μg/mL and 0.04μg/mL. Stress degradation result shows that montelukast sodium was sensitive to photo degradation, oxidation and acid hydrolysis. Oxidative degradation kinetic study of montelukast sodium followed first order reaction, with r2 =0.9877, apparent degradation rate constant, k= 0.1066 h-1, t1/2= 6.6151 hr and t90% = 1.0118hr. In conclusion, HPLC-UV method was successfully developed and validated for determination of montelukast sodium in chewable tablet formulation.
Involvement of pharmacists in improving medication adherence among diabetic patients is recognized globally. In Malaysian healthcare system, pharmacists are also operating health services i.e. Diabetes Medication Therapy Adherence Clinic (DMTAC). This study aimed to assess the clinical outcomes of patients managed by pharmacists (DMTAC), in a Malaysian hospital setting. This was an open labelled randomised study. Type 2 diabetes patients with HbA1c ≥8% were recruited and arbitrarily divided into the intervention group (usual care plus DMTAC) and the non-intervention group (usual care only). Those enrolled in the intervention group were scheduled for follow-up for eight consecutive visits. Improvements in lab results were compared longitudinally (pre and post analysis) between the groups. Data analysis was done using PASW 18® version. A total of 76 patients were enrolled, with 39 patients in the intervention group and 37 patients in the non-intervention group. Mean HbA1c (-0.90% vs. -0.08%, p=0.011) and fasting blood glucose levels (-3.45 mmol.l vs. +0.79 mmol/l, p=0.002) reduced significantly between the intervention group vs. non-intervention group. Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were also significantly reduced in the intervention group (TC -0.34 mmol/l, p=0.018) (LDL -0.45 mmol/l, p=0.001). In conclusion, pharmacists managed DMTAC significantly improved glycaemic control and lipid profile of diabetic patients.
Study site: Outpatient Clinic, Hospital Pulau Pinang, Malaysia
Phytochemical investigation on the dichloromethane stem bark extract of Calophyllum castaneum resulted in the isolation of five compounds, namely isoblancoic acid (1), blancoic acid (2), euxanthone (3), friedelin (4) and friedelinol (5). All these compounds were isolated for the first time from this plant. Their chemical structures were elucidated based on the spectroscopic analyses. The cytotoxicity of compounds 1-5 was assessed on a panel of cancer cell lines including bone (Saos-2, mg63), colorectal (HT29, Caco-2, HCC2998, SW48, HCT116, KM12), liver (HepG2), lung (H1299, Calu-3), and brain (C6), using 5-fluorouracil as positive control. Pronounced antiproliferative activities were observed for compound 1 which exhibited a comparable activity with the positive control, against brain (C6) and colorectal (SW48, KM12, HCT116) cancer cell lines showing IC50 values in the range of 14 to 65μM. Meanwhile, compound 5 displayed a greater cytotoxic effect showing at least 2-fold more strongly than the positive control, against C6 brain cancer cells. The assay findings have unveiled the therapeutic value of phytochemicals from Calophyllum castaneum as anti-cancer agents.
The effect of deprotenizing agents on recovery of donepezil hydrochloride in the development of a simple, rapid, selective and sensitive high performance liquid chromatography method for quantification of donepezil hydrochloride in human plasma was described. The deprotenizing agents were comprised of, perchloric acid, methanol, acetonitrile, chloroform and their mixtures. The chromatographic separation was carried out using reversed phase C18 column (Agilent Eclipse Plus C18) with UV detection at 268 nm. The mobile phase was comprised of 0.01 M potassium dihydrogen phosphate buffer, methanol and acetronitrile (50:30:20, v/v) adjusted to pH 2.7 with phosphoric acid (80%). A combination of perchloric acid and methanol gave a cleaner sample with a good recovery of donepezil hydrochloride of above 96%. The method showed intraday precision and accuracy in the range of 6.82% to 1.5% and 3.13% to 1.12% respectively, while interday precision and accuracy ranged between 1.06% to 4.71% and 13.01% to 6.43% respectively. The standard calibration curve was linear from 30ng/mL to 4000ng/mL, with a correlation coefficient of 0.9965±0.0034. The retention time of donepezil was 5.9 min with a run time of 7.0 min. The method can be applied to analyze large batch plasma samples in pharmacokinetic studies.
An easy, fast and validated RV-HPLC method was invented to quantify donepezil hydrochloride in drug solution and orally disintegrating tablet. The separation was carried out using reversed phase C-18 column (Agilent Eclipse Plus C-18) with UV detection at 268 nm. Method optimization was tested using various composition of organic solvent. The mobile phase comprised of phosphate buffer (0.01M), methanol and acetonitrile (50:30:20, v/v) adjusted to pH 2.7 with phosphoric acid (80%) was found as the optimum mobile phase. The method showed intraday precision and accuracy in the range of 0.24% to -1.83% and -1.83% to 1.99% respectively, while interday precision and accuracy ranged between 1.41% to 1.81% and 0.11% to 1.90% respectively. The standard calibration curve was linear from 0.125 μg/mL to 16 μg/mL, with correlation coefficient of 0.9997±0.00016. The drug solution was stable under room temperature at least for 6 hours. System suitability studies were done. The average plate count was > 2000, tailing factor <1, and capacity factor of 3.30. The retention time was 5.6 min. The HPLC method was used to assay donepezil hydrochloride in tablet and dissolution study of in-house manufactured donepezil orally disintegrating tablet and original Aricept.
A stability-indicating HPLC-UV method for the simultaneous determination of sildenafil citrate and dapoxetine hydrochloride in solution and tablet was developed. The mobile phase was comprised of acetonitrile and 0.2M ammonium acetate buffer. The analyte was eluted at 3.392min and 7.255min for sildenafil citrate and dapoxetine HCl respectively using gradient system at a flow rate of 1.5mL/min. The theoretical plates count was>2000, tailing factor
The rubber tree (Hevea brasiliensis) extracts are becoming increasingly visible in pharmaceutical and therapeutical research. The present study is aimed at examining the specific anti-proliferation property of H. brasiliensis latex B-serum sub-fractions against human breast cancer epithelial cell lines MCF-7 and MDA-MB231. The results showed that the latex whole B-serum and DBP sub-fraction exerted a specific anti-proliferation activity against cancer-origin cells MDA-MB231 but had little effect on non-cancer-origin cells. On the other hand, the anti-proliferative activity was diminished in the pre-heated B-serum fractions. With the low toxicity that the B-serum demonstrated previously in Brine Shrimp Lethality Test (BSLT), the present results suggest the potential use of the B-serum sub-fractions in cancer treatment.
Leukemia is a type of blood cancer where abnormal and immature leucocytes are produced in the bone marrow. Methadone hydrochloride is a man-made drug that is commonly used in the maintenance treatment for drug addiction. The objective of this research was to determine the cytotoxic activity and apoptotic effects of methadone hydrochloride treatment towards two leukemia cell lines which are CCRF-CEM and HL-60. CCRF-CEM and HL-60 cells were treated with methadone hydrochloride for 24 and 48 hours to determine the cytotoxic activity. IC50 at 24 hours obtained for CCRF-CEM was 121.6μmol/L while IC50 for HL-60 cells was 97.18μmol/L. Result obtained from DNA fragmentation assay showed no characteristic DNA ladder pattern in CCRF-CEM leukemia cells treated with methadone hydrochloride. Characteristics DNA ladder pattern was observed in methadone hydrochloride treated HL-60 cells. Formation of comets was seen in methadone hydrochloride treated CCRF-CEM and HL-60 cells with varying degree of DNA damage. The comets formed by methadone hydrochloride treated HL-60 cells were more prominent as compared to methadone-treated CCRF-CEM cells. The expression of apoptotic-related proteins in methadone-treated CCRF-CEM and HL-60 cells were checked by incubating the cell lysate with Raybio® Human Apoptosis Antibody Array. Significant alterations in expression level of apoptosis-related proteins in methadone hydrochloride treated CCRF-CEM cells were found involving upregulation of caspase-8 expression and downregulation of survivin expression. Methadone hydrochloride induced apoptosis in HL-60 cells involved upregulation of Bid and caspase-8 expression and downregulation of Bcl-2, p21 and survivin expression.
The school students are of particular importance in the HIV/AIDS awareness policies at both local and international level. This study was conducted to assess the level of knowledge of the modes of HIV transmission among urban and rural public secondary school students in Malaysia. In this cross-sectional study, post local ethics approval, 600self-administered questionnaires were randomly disseminated to students in 6 different secondary schools and areas (i.e. 3 urban schools and 3 rural schools). Data were descriptively and inferentially analyzed using Statistical Package of Social Sciences (SPSS®), version 17. The Pearson Chi-Square test was applied where applicable. Most respondents had heard about HIV (overall response rate: 96.2%). However, 8.9% of rural respondents (27/302) never heard about HIV and were excluded. Therefore, 275 urban students (Kuala Lumpur, Selangor, and Pahang) and 275 rural students (Terengganu) who successfully completed and returned the questionnaires were included in data analysis. Many respondents were female and within the age range of 15-16 years old. Most respondents in both areas knew that sharing needles can transmit HIV (93.5% urban; 97.1% rural). Out of 15 items concerning transmission modes of HIV, eight items showed significant values (p < 0.05) of rural vs. urban: saliva, urine, tears, using same swimming pool, blood transfusion, mosquito bites, sharing foods and donating blood to HIV patients. About 90.2% and 79.6% of respondents in urban and rural areas used television and newspapers as main source of knowledge on HIV, respectively. The implementation of incessant HIV and AIDS education programme could be useful in order to enhance and sustain awareness concerning HIV/AIDS among secondary school students.
In this study, the immunomodulatory effects of zerumbone isolated from Zingiber zerumbet were investigated by evaluating the effects of this compound towards the lymphocytes proliferation (mice thymocytes, mice splenocytes and human human peripheral blood mononuclear cells, PBMC), cell cycle progression and cytokine (interleukin 2 and 12) induction. Lymphocyte proliferation assay showed that zerumbone was able to activate mice thymocytes, splenocytes and PBMC at dosage dependent pattern where the best concentration was 7.5 microg/ml. Flow cytometry analysis showed the highest population of PBMC entered into G2/M phase after treatment for 72 h with 7.5 microg/ml zerumbone. The production of human interleukin-2 and human interleukin-12 cytokines in culture supernatant from zerumbone activated lymphocytes was prominently upregulated at 24 hour and decreased from 48 h to 72 h. The above results indicate that zerumbone can be used as immunomodulatory agent which can react toward the immune cell cytokine production in dosage dependent pattern.