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  1. Meka VS, Nali SR, Songa AS, Battu JR, Kolapalli VR
    Daru, 2012 Aug 30;20(1):21.
    PMID: 23351981 DOI: 10.1186/2008-2231-20-21
    The objective of the present investigation is to formulate gastro retentive floating drug delivery systems (GRFDDS) of propranolol HCl by central composite design and to study the effect of formulation variables on floating lag time, D1hr (% drug release at 1 hr) and t90 (time required to release 90% of the drug). 3 factor central composite design was employed for the development of GRFDDS containing novel semi synthetic polymer carboxymethyl ethyl cellulose (CMEC) as a release retarding polymer. CMEC, sodium bicarbonate and Povidone concentrations were included as independent variables. The tablets were prepared by direct compression method and were evaluated for in vitro buoyancy and dissolution studies. From the polynomial model fitting statistical analysis, it was confirmed that the response floating lag time and D1hr is suggested to quadratic model and t90 is suggested to linear model. All the statistical formulations followed first order rate kinetics with non-Fickian diffusion mechanism. The desirability function was used to optimize the response variables, each having a different target, and the observed responses were highly agreed with experimental values. Statistically optimized formulation was characterized by FTIR and DSC studies and found no interactions between drug and polymer. The results demonstrate the feasibility of the model in the development of GRFDDS containing a propranolol HCl. Statistically optimized formulation was evaluated for in vivo buoyancy studies in healthy humans for both fed and fasted states. From the results, it was concluded that gastric residence time of the floating tablets were enhanced at fed stage but not in fasted state.
  2. Upadhyay DK, Ibrahim MI, Mishra P, Alurkar VM, Ansari M
    Daru, 2016 Feb 29;24:6.
    PMID: 26926657 DOI: 10.1186/s40199-016-0145-x
    BACKGROUND: Cost is a vital component for people with chronic diseases as treatment is expected to be long or even lifelong in some diseases. Pharmacist contributions in decreasing the healthcare cost burden of chronic patients are not well described due to lack of sufficient evidences worldwide. In developing countries like Nepal, the estimation of direct healthcare cost burden among newly diagnosed diabetics is still a challenge for healthcare professionals, and pharmacist role in patient care is still theoretical and practically non-existent. This study reports the impact of pharmacist-supervised intervention through pharmaceutical care program on direct healthcare costs burden of newly diagnosed diabetics in Nepal through a non-clinical randomised controlled trial approach.
    METHODS: An interventional, pre-post non-clinical randomised controlled study was conducted among randomly distributed 162 [control (n = 54), test 1 (n = 54) and test 2 (n = 54) groups] newly diagnosed diabetics by a consecutive sampling method for 18 months. Direct healthcare costs (direct medical and non-medical costs) from patients perspective was estimated by 'bottom up' approach to identify their out-of-pocket expenses (1USD = NPR 73.38) before and after intervention at the baseline, 3, 6, 9 and 12 months follow-ups. Test groups' patients were nourished with pharmaceutical care intervention while control group patients only received care from physician/nurses. Non-parametric tests i.e. Friedman test, Mann-Whitney U test and Wilcoxon signed rank test were used to find the differences in direct healthcare costs among the groups before and after the intervention (p ≤ 0.05).
    RESULTS: Friedman test identified significant differences in direct healthcare cost of test 1 (p 
  3. Ali Jadoo SA, Aljunid SM, Nur AM, Ahmed Z, Van Dort D
    Daru, 2015 Feb 10;23:14.
    PMID: 25889668 DOI: 10.1186/s40199-014-0075-4
    BACKGROUND: The service weight is among several issues and challenges in the implementation of case-mix in developing countries, including Malaysia. The aim of this study is to develop the Malaysian Diagnosis Related Group (MY-DRG) case-mix pharmacy service weight in University Kebangsaan Malaysia-Medical Center (UKMMC) by identifying the actual cost of pharmacy services by MY-DRG groups in the hospital.

    METHODS: All patients admitted to UKMMC in 2011 were recruited in this study. Combination of Step-down and Bottom-up costing methodology has been used in this study. The drug and supplies cost; the cost of staff; the overhead cost; and the equipment cost make up the four components of pharmacy. Direct costing approach has been employed to calculate Drugs and supplies cost from electronic-prescription system; and the inpatient pharmacy staff cost, while the overhead cost and the pharmacy equipments cost have been calculated indirectly from MY-DRG data base. The total pharmacy cost was obtained by summing the four pharmacy components' cost per each MY-DRG. The Pharmacy service weight of a MY-DRG was estimated by dividing the average pharmacy cost of the investigated MY-DRG on the average of a specified MY-DRG (which usually the average pharmacy cost of all MY-DRGs).

    RESULTS: Drugs and supplies were the main component (86.0%) of pharmacy cost compared o overhead cost centers (7.3%), staff cost (6.5%) and pharmacy equipments (0.2%) respectively. Out of 789 inpatient MY-DRGs case-mix groups, 450 (57.0%) groups were utilized by the UKMMC. Pharmacy service weight has been calculated for each of these 450 MY-DRGs groups. MY-DRG case-mix group of Lymphoma & Chronic Leukemia group with severity level three (C-4-11-III) has the highest pharmacy service weight of 11.8 equivalents to average pharmacy cost of RM 5383.90. While the MY-DRG case-mix group for Circumcision with severity level one (V-1-15-I) has the lowest pharmacy service weight of 0.04 equivalents to average pharmacy cost of RM 17.83.

    CONCLUSION: A mixed approach which is based partly on top-down and partly on bottom up costing methodology has been recruited to develop MY-DRG case-mix pharmacy service weight for 450 groups utilized by the UKMMC in 2011.

  4. Koupaei Malek S, Gabris MA, Hadi Jume B, Baradaran R, Aziz M, Karim KJBA, et al.
    Daru, 2019 Jun;27(1):9-20.
    PMID: 30554368 DOI: 10.1007/s40199-018-0232-2
    Polyethylene glycol functionalized with oxygenated multi-walled carbon nanotubes (O-PEG-MWCNTs) as an efficient nanomaterial for the in vitro adsorption/release of curcumin (CUR) anticancer agent. The synthesized material was morphologically characterized using scanning electron microscopy, Fourier transform infrared spectroscopy and transmission electron microscopy. In addition, the CUR adsorption process was assessed with kinetic and isotherm models fitting well with pseudo-second order and Langmuir isotherms. The results showed that the proposed O-PEG-MWCNTs has a high adsorption capacity for CUR (2.0 × 103 mg/g) based on the Langmuir model. The in vitro release of CUR from O-PEG-MWCNTs was studied in simulating human body fluids with different pHs (ABS pH 5, intestinal fluid pH 6.6 and body fluid pH 7.4). Lastly, to confirm the success compliance of the O-PEG-MWCNT nanocomposite as a drug delivery system, the parameters affecting the CUR release such as temperature and PEG content were investigated. As a result, the proposed nanocomposite could be used as an efficient carrier for CUR delivery with an enhanced prolonged release property. Graphical Abstract ᅟ.
  5. Hasan M, Kumolosasi E, Jasamai M, Jamal JA, Azmi N, Rajab NF
    Daru, 2020 Jun;28(1):97-108.
    PMID: 31912375 DOI: 10.1007/s40199-019-00320-0
    BACKGROUND: Phytoestrogens are plant compounds that are structurally similar to estrogen and that possess anti-cancer properties. Previous studies have reported that coumestrol, daidzein and genistein could induce cell death by reducing Annexin A1 protein in leukemic cell lines. Annexin A1 (ANXA1) is involved in cell progression, metastasis, and apoptosis in several types of cancer cells. The present study sought to investigate if the effects of phytoestrogens on apoptosis, cell cycle arrest and phagocytosis in ANXA1-knockdown leukemic cells are mediated through ANXA1 or occurred independently.

    METHODS: Transfection of ANXA1 siRNA was conducted to downregulate ANXA1 expression in Jurkat, K562 and U937 cells. Apoptosis and cell cycle assays were conducted using flow cytometry. Western blot was performed to evaluate ANXA1, caspases and Bcl-2 proteins expression. Phagocytosis was determined using hematoxylin and eosin staining.

    RESULTS: The expression of ANXA1 after the knockdown was significantly downregulated in all cell lines. Genistein significantly induced apoptosis associated with an upregulation of procaspase-3, -9, and - 1 in Jurkat cells. The Bcl-2 expression showed no significant difference in Jurkat, K562 and U937 cells. Treatment with phytoestrogens increased procaspase-1 expression in Jurkat and U937 cells while no changes were detected in K562 cells. Flow cytometry analysis demonstrated that after ANXA1 knockdown, coumestrol and genistein caused cell cycle arrest at G2/M phase in selected type of cells. The percentage of phagocytosis and phagocytosis index increased after the treatment with phytoestrogens in all cell lines.

    CONCLUSION: Phytoestrogens induced cell death in ANXA1-knockdown leukemia cells, mediated by Annexin A1 proteins. Graphical abstract.

  6. Amran MHH, Zulfakar MH, Danik MF, Abdullah MSP, Shamsuddin AF
    Daru, 2019 Jun;27(1):191-201.
    PMID: 31020546 DOI: 10.1007/s40199-019-00262-7
    PURPOSE: Intravenous lipid emulsion (IVLE) was first used to prevent essential fatty acids deficiency. IVLE with α-tocopherol was reported to provide protection against parenteral nutrition-associated liver disease. This study aims to determine the optimal parameters and conditions in developing a physically stable IVLE from superolein palm oil (SoLE 20%) and its effect on lipid and liver profiles in an animal model.

    METHODS: SoLE 20% was prepared using superolein oil and MCT oil (1:1), stabilized with egg lecithin and homogenized using a high pressure homogenizer. Mean droplet size was used as the response variable and was measured using laser diffraction and dynamic light scattering method. Physical stability at 4 °C, 25 °C and 40 °C storage temperatures were determined based on particle size and distribution, polydispersity index, zeta potential, viscosity, vitamin E contents and pH. Sterility and pyrogenicity were also investigated. Rabbits were administered with 1.0 g/kg SoLE 20% for 5 h and repeated daily for 3 days to investigate its effect on blood lipid and liver enzymes profile.

    RESULTS: SoLE 20% was succesfully prepared using the optimized parameters of 800 psi, 7 cycles and 1.2 g lecithin. The IVLE prepared had a particle size of 252.60 ± 4.88 nm and was physically stable for 4 weeks at different storage temperatures. SoLE 20% had a high content of natural vitamin E, remained sterile and pyrogen free. It was also safe for intravenous administration and did not alter the blood lipid (p > 0.05) and liver enzymes profiles (p > 0.05) of the rabbits.

    CONCLUSION: The optimal parameters to develop a stable superolein based IVLE are 800 psi homogenization pressure, 7 homogenization cycles and using 1.2 g lecithin as the emulsifier. SoLE 20% is safe for intravenous administration and does not significantly alter lipid and liver enzymes profiles of the rabbits.

  7. Tantowi NACA, Mohamed S, Lau SF, Hussin P
    Daru, 2020 Dec;28(2):443-453.
    PMID: 32388789 DOI: 10.1007/s40199-020-00343-y
    BACKGROUND: Osteoporotic-osteoarthritis is an incapacitating musculoskeletal illness of the aged.

    OBJECTIVES: The anti-inflammatory and anti-catabolic actions of Diclofenac were compared with apigenin-C-glycosides rich Clinacanthus nutans (CN) leaf extract in osteoporotic-osteoarthritis rats.

    METHODS: Female Sprague Dawley rats were randomized into five groups (n = 6). Four groups were bilateral ovariectomised for osteoporosis development, and osteoarthritis were induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee joints. The Sham group was sham-operated, received saline injection and deionized drinking water. The treatment groups were orally given 200 or 400 mg extract/kg body weight or 5 mg diclofenac /kg body weight daily for 28 days. Articular cartilage and bone changes were monitored by gross and histological structures, micro-CT analysis, serum protein biomarkers, and mRNA expressions for inflammation and catabolic protease genes.

    RESULTS: HPLC analysis confirmed that apigenin-C-glycosides (shaftoside, vitexin, and isovitexin) were the major compounds in the extract. The extract significantly and dose-dependently reduced cartilage erosion, bone loss, cartilage catabolic changes, serum osteoporotic-osteoarthritis biomarkers (procollagen-type-II-N-terminal-propeptide PIINP; procollagen-type-I-N-terminal-propeptide PINP; osteocalcin), inflammation (IL-1β) and mRNA expressions for nuclear-factor-kappa-beta NF-κβ, interleukin-1-beta IL-1β, cyclooxygenase-2; and matrix-metalloproteinase-13 MMP13 activities, in osteoporotic-osteoarthritis rats comparable to Diclofenac.

    CONCLUSION: This study demonstrates that apigenin-C-glycosides at 400 mg CN extract/kg (about 0.2 mg apigenin-equivalent/kg) is comparable to diclofenac in suppressing inflammation and catabolic proteases for osteoporotic-osteoarthritis prevention. Graphical abstract.

  8. Rabeea SA, Merchant HA, Khan MU, Kow CS, Hasan SS
    Daru, 2021 Jun;29(1):217-221.
    PMID: 33715138 DOI: 10.1007/s40199-021-00390-z
    The social restrictions amid coronavirus disease 2019 (COVID-19) pandemic have posed a serious threat to mental health and have implications in the use of medications for mental health including antidepressants (ADs). This study investigated the trends in prescriptions and costs of various ADs in England during COVID-19 pandemic. National prescribing rates and net ingredient costs (NIC) of all ADs prescriptions during 2016 to 2020 were analyed. The total number of ADs prescriptions dispensed during COVID-19 pandemic (January to December 2020) were 78 million, 4 million more than in 2019 that costed NHS England £ 139 million more than in 2019. Sertraline, an SSRI antidepressant drug, alone accounted for an extra £113 million during 2020 than in 2019. The peak dispensing for ADs was observed in March 2020 while the total costs for AD drugs peaked in April 2020. The rising prescription costs for ADs during COVID-19 pandemic is a potential cause of concern, in particular the increasing use in adolescents and younger adults needs attention, who are at a higher risk of life-threatening adverse drug reactions.
  9. Damanhuri NS, Kumolosasi E, Omar MS, Razak AFA, Mansor AH
    Daru, 2021 Jun;29(1):13-22.
    PMID: 33405191 DOI: 10.1007/s40199-020-00377-2
    BACKGROUND: P-glycoprotein (P-gp) is an Adenosine triphosphate (ATP) dependent drug-efflux pump which is located abundantly in the stomach and protects the gut mucosa from xenobiotic.

    OBJECTIVE: The purpose of this study was to investigate the influence of P-gp modulation on the efficacy of treatment regimen.

    METHOD: P-gp modulation in rats was performed by using P-gp inducer (150 mg/kg rifampicin) and P-gp inhibitor (10 mg/kg cyclosporine A) for 14 days prior to be infected with Helicobacter pylori (H. pylori). The rats were further divided into groups, which were normal control, vehicle control, antibiotics and omeprazole, antibiotics only and omeprazole only for another 2 weeks of treatment. The ulcer formation and P-gp expression were determined by using macroscopic evaluation and western blot analysis, respectively.

    RESULTS: The highest P-gp expression was shown in the induced P-gp rats (2.00 ± 0.68) while the lowest P-gp expression was shown in the inhibited P-gp rats (0.45 ± 0.36) compared to the normal P-gp rats. In all groups, the rats which were infected with H. pylori, had a significant increase (p 

  10. Lim PC, Wong KL, Rajah R, Chong MF, Chow TS, Subramaniam S, et al.
    Daru, 2022 Jan 27.
    PMID: 35084705 DOI: 10.1007/s40199-021-00430-8
    PURPOSE: Tocilizumab has shown equivocal outcomes in reducing mortality in COVID-19. The corticosteroids appear to be an affordable alternative to tocilizumab. This study aims to estimate the efficacy of tocilizumab and the corticosteroids particularly dexamethasone and methylprednisolone and to identify possible determinants of their efficacy.

    METHODS: Five electronic databases were searched for studies involving tocilizumab, dexamethasone, and methylprednisolone in treating COVID-19. We included case-control and randomized or partially randomized trials. Meta-regression for patient baseline characteristics, co-medications, and tocilizumab dose regimens was performed to identify contributing factors to drug efficacy.

    RESULTS: Thirteen randomized controlled trials (RCTs) and twenty-four case-control studies were included in our meta-analysis involving 18,702 patients. Meta-analysis among the RCTs showed that a summary estimate favoring mortality reduction (OR 0.71, 95%CI 0.55 - 0.92) contributed mainly by tocilizumab and dexamethasone. Among case-control studies, meta-analysis showed mortality reduction (OR 0.52, 95%CI 0.36 - 0.75) contributed by tocilizumab and tocilizumab-methylprednisolone combination. Methylprednisolone alone did not reduce mortality except for one study involving high dose pulse therapy. Meta-analysis also found that all three drugs did not significantly reduce mechanical ventilation (OR 0.72, 95%CI 0.32 - 1.60).

    CONCLUSION: Tocilizumab and dexamethasone emerge as viable options in reducing mortality in severe COVID-19 patients. A tocilizumab-corticosteroid combination strategy may improve therapeutic outcome in cases where single therapy fails.

  11. Hassan M, Baig AA, Attique SA, Abbas S, Khan F, Zahid S, et al.
    Daru, 2021 Jun;29(1):73-84.
    PMID: 33537864 DOI: 10.1007/s40199-020-00384-3
    PURPOSE: To predict potential inhibitors of alpha-enolase to reduce plasminogen binding of Streptococcus pneumoniae (S. pneumoniae) that may lead as an orally active drug. S. pneumoniae remains dominant in causing invasive diseases. Fibrinolytic pathway is a critical factor of S. pneumoniae to invade and progression of disease in the host body. Besides the low mass on the cell surface, alpha-enolase possesses significant plasminogen binding among all exposed proteins.

    METHODS: In-silico based drug designing approach was implemented for evaluating potential inhibitors against alpha-enolase based on their binding affinities, energy score and pharmacokinetics. Lipinski's rule of five (LRo5) and Egan's (Brain Or IntestinaL EstimateD) BOILED-Egg methods were executed to predict the best ligand for biological systems.

    RESULTS: Molecular docking analysis revealed, Sodium (1,5-dihydroxy-2-oxopyrrolidin-3-yl)-hydroxy-dioxidophosphanium (SF-2312) as a promising inhibitor that fabricates finest attractive charges and conventional hydrogen bonds with S. pneumoniae alpha-enolase. Moreover, the pharmacokinetics of SF-2312 predict it as a therapeutic inhibitor for clinical trials. Like SF-2312, phosphono-acetohydroxamate (PhAH) also constructed adequate interactions at the active site of alpha-enolase, but it predicted less favourable than SF-2312 based on binding affinity.

    CONCLUSION: Briefly, SF-2312 and PhAH ligands could inhibit the role of alpha-enolase to restrain plasminogen binding, invasion and progression of S. pneumoniae. As per our investigation and analysis, SF-2312 is the most potent naturally existing inhibitor of S. pneumoniae alpha-enolase in current time.

  12. Lim PC, Chung YY, Tan SJ, Wong TY, Permalu DD, Cheah TK, et al.
    Daru, 2021 Jun;29(1):125-132.
    PMID: 33538999 DOI: 10.1007/s40199-021-00389-6
    BACKGROUND: Millions worth of unused drugs particularly those indicated for chronic diseases such as diabetes were returned and disposed leading to substantial wastage. Use of patients' own medications (POMs) in the inpatient setting has reduced wastage and saved cost. The impact of utilizing POMs in the outpatient setting has hitherto not been determined.

    PURPOSE: This study aims to compare the cost, medication adherence and glycaemic control of utilizing POMs versus usual dispensing.

    METHODS: Prospective randomized controlled study was conducted among diabetic patients that required monthly medication refill in the Outpatient Pharmacy in 2017. Patients who consented were equally divided into POMs and control groups. Both groups brought excess medications from home at week-0 and week-12. Patients in the POMs group brought excess medications monthly and sufficient amount of drugs were added until the next refill date. Drugs were dispensed as usual in the control group. Total cost consisting of the cost of drugs, staff and building was calculated. Glycosylated haemoglobin (HbA1c) was measured at baseline and week-12. Adherence was measured based on pill counting.

    RESULTS: Thirty patients aged 56.77 ± 14.67 years with 13.37 ± 7.36 years of diabetes participated. Baseline characteristics were similar between the groups. POMs minimized the total cost by 38.96% which translated to a cost saving of USD 42.76 ± 6.98, significantly different versus USD 0.02 ± 0.52 in the control group, p = 0.025. Mean HbA1c reduced significantly (-0.79%, p = 0.016) in the POMs group but not significant in the control group (-0.11%, p = 0.740). Medication adherence improved significantly in both groups at week-12 (p 

  13. Idris MKH, Hasham R, Ismail HF
    Daru, 2022 Dec;30(2):253-272.
    PMID: 35922691 DOI: 10.1007/s40199-021-00414-8
    BACKGROUND: Metabolic syndrome (MetS) is a risk factor for prostate cancer (PCa) progression. Thus, this life-threatening disease demands a proactive treatment strategy. Andrographis paniculata (AP) is a promising candidate with various medicinal properties. However, the bioactivity of AP is influenced by its processing conditions especially the extraction solvent.

    OBJECTIVE: In the present study, bioassay-guided screening technique was employed to identify the best AP extract in the management of MetS, PCa, and MetS-PCa co-disease in vitro.

    METHODS: Five AP extracts by different solvent systems; APE1 (aqueous), APE2 (absolute methanol), APE3 (absolute ethanol), APE4 (40% methanol), and APE5 (60% ethanol) were screened through their phytochemical profile, in-vitro anti-cancer, anti-obese, and anti-hyperglycemic properties. The best extract was further tested for its potential in MetS-induced PCa progression.

    RESULTS: APE2 contained the highest andrographolide (1.34 ± 0.05 mg/mL) and total phenolic content (8.85 ± 0.63 GAE/gDW). However, APE3 has the highest flavonoid content (11.52 ± 0.80 RE/gDW). APE2 was also a good scavenger of DPPH radicals (EC50 = 397.0 µg/mL). In cell-based assays, among all extracts, APE2 exhibited the highest antiproliferative activity (IC50 = 57.5 ± 11.8 µg/mL) on DU145 cancer cell line as well as on its migration activity. In in-vitro anti-obese study, all extracts significantly reduced lipid formation in 3T3-L1 cells. The highest insulin-sensitizing and -mimicking actions were exerted by both APE2 and APE3. Taken together, APE2 showed collectively good activity in the inhibition of PCa progression and MetS manifestation in vitro, compared to other extracts. Therefore, APE2 was further investigated for its potential to intervene DU145 progression induced with leptin (10-100 ng/mL) and adipocyte conditioned media (CM) (10% v/v). Interestingly, APE2 significantly diminished the progression of the cancer cell that has been pre-treated with leptin and CM through cell cycle arrest at S phase and induction of cell death.

    CONCLUSION: In conclusion, AP extracts rich with andrographolide has the potential to be used as an alternative to ameliorate PCa progression induced by factors highly expressed in MetS.

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