Simultaneous determination of tramadol and paracetamol in human plasma using LC-MS/MS and application in bioequivalence study of -fixed-dose combination.

The study aimed to develop a sensitive and high-throughput liquid chromatography coupled with tandem mass spectrometry method to quantify concentrations of tramadol and paracetamol simultaneously in human plasma. Sample preparation involved single-step protein precipitation using methanol and two deuterated internal standards, tramadol D6 and paracetamol D4. Agilent Poroshell 120 EC-C18 (100 × 2.1 mm, 2.1 µm) analytical column was employed to achieve chromatographic separation. Detection was in positive ion multiple reaction monitoring mode. A tailing factor (Tf) of <1.2, separation factor (K prime) of >1.5 from the column dead time and signal-to-noise (S/N) ratio >10, were obtained for analytes and internal standards. The standard curve was linear over the concentration range of 2.5-500.00 ng/mL for tramadol and 0.025-20.00 µg/mL for paracetamol. A small injection volume of 1 µL, low flow rate of 440 µL/min and short analysis time of 3.5 min reduced the solvent consumption, analysis cost and system contamination. The results of method validation parameters fulfilled the acceptance criteria of bioanalytical guidelines. The method was successfully applied to a bioequivalence study of fixed-dose combination products of tramadol and paracetamol in Malaysian healthy subjects.

Orally Disintegrating Film: A Review of Its Formulation and Manufacturing Method

@#Oral route drug delivery system is still considered as the most convenient and patient friendly drug delivery route. Over the decades, many research has been performed to improve the functionality oral dosage form. Orally disintegrating film (ODF) is a newer oral drug delivery system, which is in the form of a thin film that will disintegrate in the oral cavity within a matter of seconds. The aim of this review paper is to recap ODF, its benefits, formulation contents and manufacturing method. With more research and development work has been conducted on ODF, the dosage form is expected to be manufactured and scaled up to be commercializable products to be sold in the market.

Comparison of Microemulsion and Solvent Evaporation Technique for Solubility Enhancement of Amlodipine Besylate

@#Introduction: Amlodipine besylate is a calcium channel blocker indicated for hypertension and angina. It is described as slightly soluble in water and due to its limited solubility, it may result in poor bioavailability. The aim of this study is to enhance the solubility of amlodipine besylate using solvent evaporation method and microemulsion technique and to compare the two methods. Method: Solid dispersions (SD) of amlodipine besylate were developed by employing solvent evaporation method. PEG6000 was the polymer of choice and different drug:polymer ratios were used. Evaluation of the prepared SDs include solubility studies, dissolution studies and scanning electron microscopy (SEM). As for the microemulsion technique, microemulsions were prepared by phase titration method and the optimized microemulsion formulation was then characterized for solubility studies and dissolution studies. Results: SD3 with drug:polymer ratio of 1:4 achieved the highest solubility which was 96.97 mg/ml ± 0.92 whereas the solubility of the optimized microemulsion was found to be 112.54 mg/ml ± 0.92. In solvent evaporation method, as the drug:polymer ratio increases, the solubility and dissolution rate of SDs increases. Conclusion: The two methods had significantly enhance the solubility of amlodipine besylate however the microemulsion technique showed better solubility profile.

Risk factors affecting COVID-19 case fatality rate: A quantitative analysis of top 50 affected countries

BackgroundLatest clinical data on treatment on coronavirus disease 2019 (COVID-19) indicated that older patients and those with underlying history of smoking, hypertension or diabetes mellitus might have poorer prognosis of recovery from COVID-19. We aimed to examine the relationship of various prevailing population-based risk factors in comparison with mortality rate and case fatality rate (CFR) of COVID-19. MethodsDemography and epidemiology data which have been identified as verified or postulated risk factors for mortality of adult inpatients with COVID-19 were used. The number of confirmed cases and the number of deaths until April 16, 2020 for all affected countries were extracted from Johns Hopkins University COVID-19 websites. Datasets for indicators that are fitting with the factors of COVID-19 mortality were extracted from the World Bank database. Out of about 185 affected countries, only top 50 countries were selected to be analyzed in this study. The following seven variables were included in the analysis, based on data availability and completeness: 1) proportion of people aged 65 above, 2) proportion of male in the population, 3) diabetes prevalence, 4) smoking prevalence, 5) current health expenditure, 6) number of hospital beds and 7) number of nurses and midwives. Quantitative analysis was carried out to determine the correlation between CFR and the aforementioned risk factors. ResultsUnited States shows about 0.20% of confirmed cases in its country and it has about 4.85% of CFR. Luxembourg shows the highest percentage of confirmed cases of 0.55% but a low 2.05% of CFR, showing that a high percentage of confirmed cases does not necessarily lead to high CFR. There is a significant correlation between CFR, people aged 65 and above (p = 0.35) and diabetes prevalence (p = 0.01). However, in our study, there is no significant correlation between CFR of COVID-19, male gender (p = 0.26) and smoking prevalence (p = 0.60). ConclusionOlder people above 65 years old and diabetic patients are significant risk factors for COVID-19. Nevertheless, gender differences and smoking prevalence failed to prove a significant relationship with COVID-19 mortality rate and CFR.

Convalescent plasma: A potential therapeutic option for COVID-19 patients

The new coronavirus disease (COVID-19) outbreak has challenged us to take unprecedented steps to bring this pandemic under control. In view of the urgency of this situation, convalescent plasma which was used in previous coronavirus outbreaks has emerged as one of the treatment options in this current pandemic. This is mainly due to the fact that convalescent plasma has been studied in a few case series with promising outcomes. In addition, on-going large clinical trials aimed to further evaluate the effectiveness, safety, and optimal dosage, duration and timing of administration of convalescent plasma are indeed revealing a certain level of promising results. Therefore, this article aims to provide an overview of possible mechanisms of actions of convalescent plasma, its benefits and its level of usage safeness by summarizing the existing evidence on the use of convalescent plasma in COVID-19 patients.

Cold chain time- and temperature-controlled transport of vaccines: a simulated experimental study

Prescribing Trend And Drug Cost Analysis Of Oral Hypoglycemic Agents Using Drug Utilisation Review

@#Drug utilization of oral hypoglycemic agents (OHAs) in a private healthcare setting is useful to examine the prescribing pattern of OHAs, especially the newer fixed dose combination (FDC) products. This study was aimed to evaluate the prescribing pattern of OHAs indicated for Type 2 diabetes mellitus (T2DM), to determine the costs of OHAs prescribed and total cost per prescription in the treatment of T2DM in an outpatient department of a private hospital located in central Malaysia. Retrospective review of electronic medical record (EMR) study design was adopted. Patient’s demographic characteristics, medications prescribed, prescribers’ details and cost per prescription were documented. Defined daily dose (DDD) of OHAs and drug cost were calculated. Research ethics protocol was approved and no personal data was collected. Out of the 396 EMR screened, 135 fulfilled the inclusion criteria and subsequently were analysed. In term of demography, mean age of the sample was 51 years old with 59% were male and ethnicity composition of 71% Malay and 19% Chinese. Metformin and “metformin+dipeptidyl peptidase-4 inhibitor” (DPP-4i) were the most commonly prescribed single-drug and FDC OHA, respectively. Average cost of OHAs and total cost per prescription was less than USD 68 and USD 185, respectively. Meanwhile, FDC covered 28.91% of incidences of prescriptions, but 44.6% of cost and SGTL-2i covered 9% incidences of prescriptions and 16.29% of cost. Prescribing pattern of OHA was appropriate based on patient’s T2DM diagnosis, however, dosage given were not in accordance with WHO DDD.

Surface Dissolution UV Imaging for Investigation of Dissolution of Poorly Soluble Drugs and Their Amorphous Formulation.

The aim of this study is to investigate the dissolution properties of poorly soluble drugs from their pure form and their amorphous formulation under physiological relevant conditions for oral administration based on surface dissolution ultraviolet (UV) imaging. Dissolution of two poorly soluble drugs (cefuroxime axetil and itraconazole) and their amorphous formulations (Zinnat® and Sporanox®) was studied with the Sirius Surface Dissolution Imager (SDI). Media simulating the fasted state conditions (compendial and biorelevant) with sequential media/flow rate change were used. The dissolution mechanism of cefuroxime axetil in simulated gastric fluid (SGF), fasted state simulated gastric fluid (FaSSGF) and simulated intestinal fluid (SIF) is predominantly swelling as opposed to the convective flow in fasted state simulated intestinal fluid (FaSSIF-V1), attributed to the effect of mixed micelles. For the itraconazole compact in biorelevant media, a clear upward diffusion of the dissolved itraconazole into the bulk buffer solution is observed. Dissolution of itraconazole from the Sporanox® compact is affected by the polyethylene glycol (PEG) gelling layer and hydroxypropyl methylcellulose (HPMC) matrix, and a steady diffusional dissolution pattern is revealed. A visual representation and a quantitative assessment of dissolution properties of poorly soluble compounds and their amorphous formulation can be obtained with the use of surface dissolution imaging under in vivo relevant conditions.

6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson's Disease Model for Dopaminergic Neuroregeneration.

Conventional mammalian models of neurodegeneration are often limited by futile axonogenesis with minimal functional recuperation of severed neurons. The emergence of zebrafish, a non-mammalian model with excellent neuroregenerative properties, may address these limitations. This study aimed to establish an adult zebrafish-based, neurotoxin-induced Parkinson's disease (PD) model and subsequently validate the regenerative capability of dopaminergic neurons (DpN). The DpN of adult male zebrafish (Danio rerio) were lesioned by microinjecting 6-hydroxydopamine (6-OHDA) neurotoxin (6.25, 12.5, 18.75, 25, 37.5, 50 and 100 mg/kg) into the ventral diencephalon (Dn). This was facilitated by an optimised protocol that utilised 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate (DiI) dye to precisely identify the injection site. Immunostaining was utilised to identify the number of tyrosine hydroxylase immunoreactive (TH-ir) DpN in brain regions of interest (i.e. olfactory bulb, telencephalon, preoptic area, posterior tuberculum and hypothalamus). Open tank video recordings were performed for locomotor studies. The Dn was accessed by setting the injection angle of the microinjection capillary to 60° and injection depth to 1200 µm (from the exposed brain surface). 6-OHDA (25 mg/kg) successfully ablated >85% of the Dn DpN (preoptic area, posterior tuberculum and hypothalamus) whilst maintaining a 100% survival. Locomotor analysis of 5-min recordings revealed that 6-OHDA-lesioned adult zebrafish were significantly (p < 0.0001) reduced in speed (cm/s) and distance travelled (cm). Lesioned zebrafish showed full recovery of Dn DpN 30 days post-lesion. This study had successfully developed a stable 6-OHDA-induced PD zebrafish model using a straightforward and reproducible approach. Thus, this developed teleost model poses exceptional potentials to study DpN regeneration.

Medication use and adherence among multi-ethnic community-dwelling older adults in Malaysia.

AIM: The present study assessed adherence, barriers, belief and awareness towards the use of medications among multi-ethnic community-dwelling older adults in Malaysia. Medication accessibility, expenditure and perceptions towards medicine labeling among older adults were also evaluated. METHODS: A cross-sectional study was carried out in the central region of Malaysia from January to August 2015. The older adults enrolled in an ongoing prospective community-based geriatric cohort study and prescribed with medicines were interviewed using a 50-item validated questionnaire. RESULTS: Of the 79 older adults interviewed, 39.2% had ≥4 prescribed medications. Most obtained their medications free-of-charge from government hospitals (66, 83.5%). Nearly half (35, 44.3%) had trouble reading labels for medicines that they had received. Chinese older adults (P = 0.001) and those with lower monthly household income (P < 0.001) expressed difficulty in reading medication labels. Most (59, 75.0%) were unable to differentiate between generic and brand names of the medications, and 49.4% of the older adults did not know that all medicines had to be registered with the Ministry of Health, Malaysia. Most older adults had positive beliefs about the necessity of their medications, and 50.6% (n = 40) reported high medication adherence. The medication adherence score was negatively correlated with the concerns score (r = -0.5, P < 0.001). CONCLUSIONS: The findings from the present study provide a unique insight into the diversity of medication use among multiethnic community-dwelling older adults. Although high adherence to medications and positive beliefs about the necessity of medications were reported by the older adults, their knowledge about medications remained insufficient and they had difficulty in reading medication labels. Geriatr Gerontol Int 2017; 17: 1214-1220.

Dikir Farmasi: folk songs for health education.

In an effort to enhance public awareness, we develop Dikir Farmasi as an innovative approach to deliver health information. Dikir Farmasi combines the elements of dikir barat (a type of traditional folk song rhythm) and traditional sketches which are popular in the state of Kelantan, Malaysia. These sketches and dikir barat rhythmic songs, with lyrics touch on issues such as drug abuse and regulation are presented in an entertaining and humorous way. Health promotion messages are disseminated using Dikir Farmasi in the form of compact disks, video compact disks, stage performance, exhibition, social media, printed media (signboard, brochure and flyer).

Empirical use of antibiotic therapy in the prevention of early onset sepsis in neonates: a pilot study.

INTRODUCTION: To identify and assess the characteristics, risk and outcome of neonates treated with empiric antibiotics for suspected early onset sepsis (EOS). MATERIAL AND METHODS: This is a retrospective study conducted at a Malaysian government hospital. Records of neonatal patients admitted within 72 h of life and prescribed with empirical antibiotic therapy for suspected EOS were reviewed. RESULTS: Three hundred and twenty-three cases met the inclusion criteria and were divided into gestational age (premature < 36 weeks; term ≥ 37 weeks) and birth weight (low birth weight (LBW) < 2.5 kg; normal body weight (NBW) ≥ 2.5 kg) groups. Premature (n = 197) and LBW (n = 194) neonates required significantly longer hospital stay, a higher degree of ventilator support and more surfactant (p = 0.001). More than 90.0% of premature and LBW neonates were diagnosed with respiratory distress syndrome, congenital pneumonia and presumed sepsis. Term (n = 123) and NBW (n = 129) neonates had greater maternal risk factors, especially meconium-stained amniotic fluid (MSAF) and perinatal asphyxia. The incidence of demonstrated EOS was 3.1%. Crystalline penicillin plus gentamicin was the standard therapy for all groups and was started within 24 h of life, with a mean treatment duration of ∼4 days. The treatment success rate was 89.0%, and only LBW neonates showed a higher risk of overall treatment failure (OR = 3.75; 95% CI: 1.22-11.53). Seventy-four percent of term and NBW neonates discharged well, while 42.0% of premature and LBW neonates required referral. CONCLUSIONS: Crystalline penicillin plus gentamicin prescribed within 24 h of life is effective in the prevention of EOS. However, low birth weight neonates have a higher risk of treatment failure.

Immunopotentiality of Ayurvedic polyherbal formulations “Saribadi” and “Anantamul Salsa” with augmentation of IgM production and lymphocytes proliferation: A preliminary study

Objective To assess the immunopotentiality of Ayurvedic polyherbal preparations, “Saribadi” and “Anantamul Salsa”. Methods Freshly prepared BALB/c mice splenocytes were cultured with “Saribadi” or “Anantamul Salsa” treatment [doses of 0.25%, 0.50%, 0.75%, 1.00%, 1.50%, 2.00%, 3.00% and 4.00% (v/v)] at 37 °C for 5 days. The immunoglobulin M (IgM) production and lymphocytes proliferation were determined by ELISA and MTT methods, respectively. Endotoxin contamination was assessed by treating the preparations with polymyxin B. Results The doses of “Saribadi” [0.25%, 0.50%, 0.75% and 1.00% (v/v)] significantly increased IgM productions (0.966, 0.728, 0.695 and 0.615 μg/mL vs. control 0.265 μg/mL) and lymphocytes proliferation [absorbance 0.311, 0.394, 0.372 and 0.334 optical density (OD) vs. control 0.162 OD]. Similarly, the doses of “Anantamul Salsa” [0.50%, 0.75%, 1.00% and 1.50% (v/v)] promoted IgM productions (0.933, 0.919, 0.917 and 0.892 μg/mL vs. control 0.502 μg/mL) and the doses of “Anantamul Salsa” [0.50%, 0.75%, 1.00%, 1.50%, 2.00%, and 3.00% (v/v)] stimulated lymphocytes proliferation (absorbance 0.395, 0.326, 0.440, 0.398, 0.452 and 0.355 OD vs. control 0.199 OD). The activity of “Saribadi” and “Anantamul Salsa” was not retarded by the treatment of preparations with polymyxin B. Conclusions Immunomodulatory activity of “Saribadi” and “Anantamul Salsa” was unveiled for the first time. “Saribadi” and “Anantamul Salsa” possess immunostimulating potential acting through the induction of lymphocyte proliferation and IgM production. These preparations may be useful in strengthening immune responses. However, further cellular and in vivo studies are required.