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.

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.