Hamidon Basri

Formulation optimization of palm kernel oil esters nanoemulsion-loaded with chloramphenicol suitable for meningitis treatment

Palm kernel oil esters nanoemulsion-loaded with chloramphenicol was optimized using response surface methodology (RSM), a multivariate statistical technique. Effect of independent variables (oil amount, lecithin amount and glycerol amount) toward response variables (particle size, polydispersity index, zeta potential and osmolality) were studied using central composite design (CCD). RSM analysis showed that the experimental data could be fitted into a second-order polynomial model. Chloramphenicol-loaded nanoemulsion was formulated by using high pressure homogenizer. The optimized chloramphenicol-loaded nanoemulsion response values for particle size, PDI, zeta potential and osmolality were 95.33nm, 0.238, -36.91mV, and 200mOsm/kg, respectively. The actual values of the formulated nanoemulsion were in good agreement with the predicted values obtained from RSM. The results showed that the optimized compositions have the potential to be used as a parenteral emulsion to cross blood-brain barrier (BBB) for meningitis treatment.

Genetic Polymorphisms and Drug Interactions Leading to Clopidogrel Resistance: Why the Asian Population Requires Special Attention

ABSTRACT Ischemic heart disease and stroke are the two leading causes of death worldwide. Antiplatelet therapy plays the most significant role in the management of these cardiovascular and cerebrovascular occlusive events to prevent recurrent ischemic attack. Clopidogrel, an antiplatelet drug, is widely prescribed either alone or in combination with aspirin as dual antiplatelet therapy for the prevention of vascular occlusive events. The antiplatelet response to clopidogrel varies widely. Hyporesponders and nonresponders are likely to have adverse cardiovascular events during follow-up. Some drugs, such as proton pump inhibitors (omeprazole), calcium channel blockers, selective serotonin reuptake inhibitors (nefazadone), coumarin derivatives (phenprocoumon), benzodiazepines, sulfonylurea, erythromycin, and itraconazole, decrease the antiplatelet effect of clopidogrel when administered concomitantly. Decreased response to clopidogrel is common among Asians due to genetic polymorphisms associated with clopidogrel resistance, and it is nearly 70% in some of the Asian communities. It is necessary to study Asian populations, because there are a large number of Asians throughout the world due to increased migration. Current guidelines do not make genetic testing or platelet response testing mandatory prior to clopidogrel prescription. Therefore, it is important for clinicians treating Asian patients to keep in mind the interindividual variability in response to clopidogrel when prescribing the drug.

Phase Behaviour, Formation and Characterization of Palm-Based Esters Nanoemulsion Formulation containing Ibuprofen

Palm-based esters, synthesized through enzymatic transesterification of palm oil fractions with oleyl alcohol have potential application in pharmaceutical formulations. The phase behaviour of palm-based esters containing ibuprofen with surfactant of different HLB values was investigated for topical delivery system. The surfactants were Tween 85, Tween 60 and Tween 80, and the palm-based esters were palm oil esters (POEs) and palm kernel oil esters (PKOEs). Ternary phase diagrams of palm-based esters: Ibuprofen/surfactant/water systems were constructed. Three distinct regions were observed in the phase diagrams; isotropic liquid region, L 1 , liquid crystalline region, L c and multiphase region, M. Nanoemulsions were prepared spontaneously by the addition of water to oil:ibuprofen/surfactant mixtures based on the ternary phase diagrams constructed. Formulations from the PKOEs:Ibuprofen/Tween 80/water systems were selected due to the presence of large isotropic liquid region, which suggested that this region was suitable to be used in producing nanoemulsions. Particle size analysis showed that the mean particle sizes of these formulations ranged from 10 nm to 70 nm. Zeta potential analysis for all formulations showed negative values from -4 to -8 mV. Stability studies showed that, after 4 h of stirring at room temperature (25°C), the formulations were stable under centrifugation test at 4000 rpm for 15 min. Stability under different storage temperature showed that at 25°C, the four formulations, F1, F2, F3 and F4 were stable with no phase separation for the duration of 1 month. However, when these formulations were stored at 45°C and 4°C, respectively, only F3 and F4 were observed to be stable. These two formulations have the potential to be used for topical delivery of ibuprofen.

Formulation Optimization of a Palm-Based Nanoemulsion System Containing Levodopa

Response surface methodology (RSM) was utilized to investigate the influence of the main emulsion composition; mixture of palm and medium-chain triglyceride (MCT) oil (6%–12% w/w), lecithin (1%–3% w/w), and Cremophor EL (0.5%–1.5% w/w) as well as the preparation method; addition rate (2–20 mL/min), on the physicochemical properties of palm-based nanoemulsions. The response variables were the three main emulsion properties; particle size, zeta potential and polydispersity index. Optimization of the four independent variables was carried out to obtain an optimum level palm-based nanoemulsion with desirable characteristics. The response surface analysis showed that the variation in the three responses could be depicted as a quadratic function of the main composition of the emulsion and the preparation method. The experimental data could be fitted sufficiently well into a second-order polynomial model. The optimized formulation was stable for six months at 4 °C.

Modification of palm kernel oil esters nanoemulsions with hydrocolloid gum for enhanced topical delivery of ibuprofen

Introduction During recent years, there has been growing interest in the use of nanoemulsion as a drug-carrier system for topical delivery. A nanoemulsion is a transparent mixture of oil, surfactant and water with a very low viscosity, usually the product of its high water content. The present study investigated the modification of nanoemulsions with different hydrocolloid gums, to enhanced drug delivery of ibuprofen. The in vitro characterization of the initial and modified nanoemulsions was also studied. Methods A palm kernel oil esters nanoemulsion was modified with different hydrocolloid gums for the topical delivery of ibuprofen. Three different hydrocolloids (gellan gum, xanthan gum, and carrageenan) were selected for use. Ternary phase diagrams were constructed using palm kernel oil esters as the oil, Tween 80 as the surfactant, and water. Nanoemulsions were prepared by phase inversion composition, and were gradually mixed with the freshly prepared hydrocolloids. The initial nanoemulsion and modified nanoemulsions were characterized. The abilities of the nanoemulsions to deliver ibuprofen were assessed in vitro, using a Franz diffusion cell fitted with rat skin. Results No significant changes were observed in droplet size (~16–20 nm) but a significant difference in polydispersity indexes were observed before and after the modification of nanoemulsions using gellan gum, carrageenan, and xanthan gum. The zeta potentials of the initial nanoemulsions (−11.0 mV) increased to −19.6 mV, −13.9 mV, and −41.9 mV, respectively. The abilities of both the initial nanoemulsion (T802) and the modified nanoemulsion to deliver ibuprofen through the skin were evaluated in vitro, using Franz diffusion cells fitted with rat skin. The in vitro permeation data showed that the modified nanoemulsion (Kp value of 55.4 × 10−3 cm · h−1) increased the permeability of ibuprofen 4.40 times over T802 (Kp value of 12.6 × 10−3 cm · h−1) (P < 0.05). Conclusion The modified nanoemulsion may be a promising vehicle to enhance the permeation of ibuprofen for topical delivery.

A study of intima media thickness and their cardiovascular risk factors in patients with Psoriatic arthritis

INTRODUCTION Psoriatic Arthritis (PsA) is an inflammatory arthritis associated with Psoriasis. Its recognition as an inflammatory disease distinct from Rheumatoid Arthritis has put forward for consideration several questions regarding its specific CVS mortality and morbidity (9, 11, 16, 26). Carotid intima media thickness is a useful surrogate and sensitive marker to determine atherosclerosis even in its subclinical stages (6, 14, 22, 27, 32). OBJECTIVE Prevalence of carotid intima media thickness in patients with Psoriatic arthritis is unknown in Asian population. We aim to identify the presence of subclinical atherosclerosis in patients with psoriatic arthritis and disease activity association and its predictors in a series of patients with PsA attended to the rheumatology clinic, tertiary hospitals. METHODS A total of 63 patients with PsA who fulfilled the CASPAR criteria were recruited from UKM Medical Centre and Hospital Putrajaya. Common carotid intima media thickness (IMT) was measured in both right and left carotid artery by using high resolution B-mode ultrasound. This was a cross sectional study first done in Malaysia for PsA patients. RESULTS The positive IMT (IMT > 1.00 mm) among PsA was observed in 10 out of 63 patients (15.9 %) regardless of background cardiovascular risk. The mean +/- SD of IMT was 0.725 +/-0.260 mm for this study. Variables significantly associated with positive IMT (p < 0.05) included age at the time of study (p = 0.005), waist circumference (p = 0.001), Hypertension (p = 0.007), Diabetes (p = 0.002) and Metabolic syndrome (p = 0.001) and not associated with gender, ethnicity, duration of PsA disease, pattern of PsA, disease activity and severity. Above all, only age had positive IMT independent predictor (p = 0.032), with OR 1.116; 95 % CI (1.010-1.234). CONCLUSIONS There was a significant association between CVS risk and positive Intima Media Thickness in Psoriatic Arthritis patients. Otherwise, there was no association in disease activity, disease severity and DMARDS therapy with positive Intima Media Thickness in Psoriatic Arthritis patients. The study was approved by Research and Ethics Committee of the faculty of medicine, Universiti Kebangsaan Malaysia with project code FF-114-2008 and by Community Research Center (CRC) of National Institutes of Health (NIH) for the case study in Hospital Putrajaya with the project code NMRR-08-970-2125.

Ultrasonic emulsification of parenteral valproic acid-loaded nanoemulsion with response surface methodology and evaluation of its stability

Response surface methodology (RSM) was used to optimize the formulation of a nanoemulsion for central delivery following parenteral administration. A mixture of medium-chain triglyceride (MCT) and safflower seed oil (SSO) was determined as a sole phase from the emulsification properties. Similarly, a natural surfactant (lecithin) and non-ionic surfactant (Tween 80) (ratio 1:2) were used in the formulation. A central composite design (CCD) with three-factor at five-levels was used to optimize the processing method of high energy ultrasonicator. Effects of pre-sonication ultrasonic intensity (A), sonication time (B), and temperature (C) were studied on the preparation of nanoemulsion loaded with valproic acid. Influence of the aforementioned specifically the effects of the ultrasonic processing parameters on droplet size and polydispersity index were investigated. From the analysis, it was found that the interaction between ultrasonic intensity and sonication time was the most influential factor on the droplet size of nanoemulsion formulated. Ultrasonic intensity (A) significantly affects the polydispersity index value. With this optimization method, a favorable droplet size of a nanoemulsion with reasonable polydispersity index was able to be formulated within a short sonication time. A valproic acid loaded nanoemulsion can be obtained with 60% power intensity for 15 min at 60 °C. Droplet size of 43.21±0.11 nm with polydispersity index of 0.211 were produced. The drug content was then increased to 1.5%. Stability study of nanoemulsion containing 1.5% of valproic acid had a good stability as there are no significant changes in physicochemical aspects such as droplet size and polydispersity index. With the characteristisation study of pH, viscosity, transmission electron microscope (TEM) and stability assessment study the formulated nanoemulsion has the potential to penetrate blood-brain barrier in the treatment of epilepsy.

Beneficial effects of TQRF and TQ nano- and conventional emulsions on memory deficit, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble Aβ levels in high fat-cholesterol diet-induced rats

The study determined the effect of thymoquinone rich fraction (TQRF) and thymoquinone (TQ) in the forms of nano- and conventional emulsions on learning and memory, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble β-amyloid (Aβ) levels in rats fed with a high fat-cholesterol diet (HFCD). The TQRF was extracted from Nigella sativa seeds using a supercritical fluid extraction system and prepared into nanoemulsion, which later named as TQRF nanoemulsion (TQRFNE). Meanwhile, TQ was acquired commercially and prepared into thymoquinone nanoemulsion (TQNE). The TQRF and TQ conventional emulsions (CE), named as TQRFCE and TQCE, respectively were studied for comparison. Statin (simvastatin) and non-statin (probucol) cholesterol-lowering agents, and a mild-to-severe Alzheimers disease drug (donepezil) were served as control drugs. The Sprague Dawley rats were fed with HFCD for 6 months, and treated with the intervention groups via oral gavage daily for the last 3 months. As a result, HFCD-fed rats exhibited hypercholesterolaemia, accompanied by memory deficit, increment of lipid peroxidation and soluble Aβ levels, decrement of total antioxidant status and down-regulation of antioxidants genes expression levels. TQRFNE demonstrated comparable effects to the other intervention groups and control drugs in serum biomarkers as well as in the learning and memory test. Somehow, TQRFNE was more prominent than those intervention groups and control drugs in brain biomarkers concomitant to gene and protein expression levels. Supplementation of TQRFNE into an HFCD thus could ameliorate memory deficit, lipid peroxidation and soluble Aβ levels as well as improving the total antioxidant status and antioxidants genes expression levels.

Guillain–Barré syndrome complicating dengue fever: Two case reports

Guillain–Barré syndrome is a rare neurological manifestation associated with dengue infection. More common antecedent infections include Campylobacter jejuni and Cytomegalovirus infection. Here, we report two cases of Guillain–Barré syndrome complicating dengue infection.

Nanoemulsion-based Parenteral Drug Delivery System of Carbamazepine: Preparation, Characterization, Stability Evaluation and Blood-Brain Pharmacokinetics

Carbamzepine (CBZ) was encapsulated in a parenteral oil-in-water nanoemulsion, in an attempt to improve its bioavailability. The particle size, polydispersity index and zeta potential were measured using dynamic light scattering. Other parameters such as pH, osmolality, viscosity, drug loading efficiency and entrapment efficiency were also recorded. Transmission electron microscopy revealed that emulsion droplets were almost spherical in shape and in the nano-range. The in vitro release profile was best characterized by Higuchis equation. The parenteral nanoemulsion of CBZ showed significantly higher AUC0→5, AUC0→∞, AUMC0→5, AUMC0→∞, Cmax and lower clearance than that of CBZ solution in plasma. Additionally, parenteral nanoemulsion of CBZ showed significantly higher AUC0→∞, AUMC0→∞ and Cmaxthan that of CBZ solution in brain. The parenteral nanoemulsion of CBZ could therefore use as a carrier, worth exploring further for brain targeting.