Gastrointestinal transit and bioavailability of a novel sustained release theophylline formulation.

A novel multiunit sustained release theophylline preparation has been formulated and assessed. Spherical pellets containing 80% theophylline were formed using an extrusion/spheronisation technique before being coated with an ethylcellulose-methylcellulose mixture using a fluidized bed coater. In-vitro dissolution studies established that satisfactory pH-independent release profiles were achieved, and that the rate of drug release could be varied in a predictable manner by manipulating the coat thickness. With additional thermal treatment of the coat, drug release was stable after storage of the products for one year. In- vivo evaluation of the preparation in healthy human volunteers, produced serum concentration profiles that were reflective of a controlled and sustained drug release, with complete bioavailability. A satisfactory correlation was also obtained between in-vitro and in-vivo results. Further comparison with a commercial preparation, Uniphyllin, showed that the two products were bioequivalent when dosed fasted. In the fed mode, the rate of theophylline absorption from Uniphyllin was significantly increased, whilst that of the novel preparation was essentially unaffected, although a slight delay in absorption was noted. However, for neither preparation was the amount absorbed influenced by food status. Gastrointestinal transit studies of the novel preparation using a gamma-scintigraphic technique, revealed that the presence of food delayed the gastric emptying, but was without influence on the small intestinal transit time. The delay in gastric emptying was associated with a delay in drug absorption. For both fed and fasted states, the rate of absorption whilst the pellets were in the stomach was slower than when the pellets were in the small intestine. The pellets were less well dispersed in the stomach than in the small intestine or colon. Moreover, whereas only 14% of drug was released in the stomach, 46% was released in the small intestine. It is interesting that the remaining 40% of the drug was taken up from the colon, which thus acts as a significant site of absorption

Electrophoresis : what does a century old technology hold for the future of separation science?

Electrophoretic separation was first demonstrated in the year of 1807 and has since been a staple tool used by biologists and chemists for more than a century since its inception. From the initial crude paper electrophoresis system to today’s modern automated electrophoresis system, the development of electrophoresis systems have been driven by the advancement of technology such as miniaturization, precision engineering, biochemistry, electrical and electronics. These advancements were introduced to meet the requirement for faster and better resolution of results. This paper reviews the evolution of the electrophoresis technology over one century and provides an insight into the possible future development of electrophoresis.Various aspects of the electrophoresis system such as the performances, designs, usages, separation phases, and biochemistry were analyzed. The technological advancements for this field have been evidenced by the increasing complexity of the electrophoresis system. A peek into the possible future for the world of electrophoresis has been provided by drawing insights from the missing links of current technologies. It is both exciting and equally perplexing to explore the promises that this seeming simple separation technology holds for the future

Neuroprotective Potentials of Natural Vitamin E for Cerebral Small Vessel Disease

Cerebral small vessel disease (CSVD) refers to a spectrum of clinical and neuroimaging findings resulting from pathological processes of various etiologies affecting cerebral arterioles, perforating arteries, capillaries, and venules. It is the commonest neurological problem that results in significant disability, but awareness of it remains poor. It affects over half of people over 65 years old and inflicts up to third of acute strokes, over 40% of dementia, and a significant decline in physical ability in otherwise asymptomatic, aging individuals. Moreover, the unifying theory for the pathomechanism of the disease remains elusive and hence the apparent ineffective therapeutic approaches. Given the growing literature for natural vitamin E (tocopherols and tocotrienols) as a potent antioxidant, this chapter attempts to consolidate the contemporary evidence to shed plausible insights on the neuroprotective potentials of natural vitamin E in addressing the heterogenous CSVD spectrum, in health and in disease

A low cost, simplified and battery-powered mobile electrophoresis system suitable as edutainment tool.

Electrophoresis originated since 1807 and has been a staple tool used by biologist and chemist over the centuries since its inception. From paper electrophoresis system to today’s modern automated electrophoresis system, the development of electrophoresis systems have been driven by the advancement of technology and also by the requirement of better and faster resolution of results. This paper reviews the progress of electrophoresis over the decades and into possible future development of electrophoresis

The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and Pharmacometabolomics

Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing. However, these methods lack precise prediction of clopidogrel outcome, often leading to insufficient prediction. Pharmacometabolomics which is an approach to identify novel biomarkers of drug response or toxicity in biofluids has been investigated to predict drug response. The advantage of pharmacometabolomics is that it does not only predict the response but also provide extensive information on the metabolic pathways implicated with the response. Integrating pharmacogenetics with pharmacometabolomics can give insight on unknown genetic and nongenetic factors associated with the response.This review aimed to review the literature on factors associated with the variable platelets reactivity response to clopidogrel, as well as appraising current methods for the personalization of clopidogrel therapy. We also aimed to review the literature on using pharmacometabolomics approach to predict drug response, as well as discussing the plausibility of using it to predict clopidogrel outcome

Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages

BACKGROUND: Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug. METHODS: Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7. RESULTS: Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2) than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine. CONCLUSION: This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro

A Validated LC Method for the Quantitation of Cefotaxime in pH-Sensitive Nanoparticles

A sensitive and rapid routine LC method was validated for measuring cefotaxime incorporated in three different pH-sensitive nanoparticles. The drug was chromatographed on a C18 reversed-phase column; the mobile phase used was 0.05 M aqueous ammonium acetate, acetonitrile and tetrahydrofuran (87:11:2, v/v) adjusted to pH 5.5 with acetic acid. The flow rate was 1 mL min(-1) and cefotaxime was quantified at 254 nm, with a sensitivity range of 0.005 AUFS. The validated method was specific, linear (R (2) a parts per thousand yen 0.999), precise and accurate in a concentration range of 0.2-50.0 mu g mL(-1). The method was rapid, selective and suitable for evaluation of cefotaxime in pH-sensitive Eudragit nanoparticles

The CYP2C19*1/*2 Genotype Does Not Adequately Predict Clopidogrel Response in Healthy Malaysian Volunteers

Background. The CYP2C19*2 allele may be associated with a reduced antiplatelet effect for clopidogrel. Here, we assessed whether CYP2C19*2 alleles correlate with clopidogrel responsiveness following the administration of clopidogrel in healthy Malaysian volunteers. Methods. Ninety volunteers were genotyped for CYP2C19*2 and CYP2C19*3 alleles. Forty-five of 90 volunteers were included in the clopidogrel response studies and triaged into three genotypes, namely, CYP2C19*1/*1 (n=17), CYP2C19*1/*2 (n=21), and CYP2C19*2/*2 (n=7). All subjects received 300 mg of clopidogrel, and platelet reactivity was assessed after a four-hour loading utilizing the VerifyNow-P2Y12 assay. Platelet activity was reported using P2Y12 reaction units (PRUs), and nonresponder status was prespecified at PRU ≥ 230. Results. Following clopidogrel intake, CYP2C19*2/*2 carriers had a significantly higher mean PRU compared to the CYP2C19*1/*2 and CYP2C19*1/*1 (291.0 ± 62.1 versus 232.5 ± 81.4 versus 147.4 ± 87.2 PRU, P<0.001) carriers. Almost half of the participants (46.7%) were found to be nonresponders (3 were CYP2C19*1/*1, 11 were CYP2C19*1/*2, and 7 were CYP2C19*2/*2). Conclusion. In healthy Malaysian volunteers, CYP2C19*2 allele was associated with a decrease in platelet responsiveness to clopidogrel. However, clopidogrel nonresponders can be found not only in the carriers of CYP2C19*2/*2, but also in the carriers of CYP2C19*1/*2 and CYP2C19*1/*1. The present paper demonstrated that genotype information does not correlate with clopidogrel response, and genotyping may represent a less robust approach compared to platelet activity testing in guiding clopidogrel therapy

Safety assessment of tocotrienol supplementation in subjects with metabolic syndrome: a randomised control trial

Previous studies have reported that tocotrienols (T3) possess many distinct properties such as antioxidant, cardioprotective, neuroprotective, anti-cancer, anti-inflammatory and anti-angiogenic, which are beneficial for the improvement of human health. However, there is limited data available on the safety assessment of T3 compared to tocopherols (T). A randomised, double-blinded, cross-over and placebo-controlled human clinical trial was conducted to determine the safety and tolerance of T3 supplementation in 31 subjects with metabolic syndrome. The subjects were supplemented with tocotrienol-rich fraction (TRF) 200 mg or placebo capsules twice daily for two weeks followed by a post-intervention visit. Results showed that T3 supplementation had no significant adverse effect on the red blood cell (RBC), white blood cell (WBC) and platelet counts between TRF (5.10 ± 0.78 × 1012 litre-1, 7.35 ± 1.59 × 109 litre-1, 279.45 ± 73.86 × 109 litre-1, respectively) and placebo interventions (5.13 ± 0.76 × 1012 litre-1, 7.25 ± 1.95 × 109 litre-1, 267.45 ± 68.72 × 109 litre-1, respectively). Measures of serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT)) and albumin did not differ between TRF (25.68 ± 10.72 IU litre-1, 38.26 ± 24.74 IU litre-1, 43.61 ± 2.26 g litre-1, respectively) and placebo interventions (27.39 ± 16.44 IU litre-1, 42.23 ± 33.58 IU litre-1, 43.68 ± 2.15 g litre-1, respectively). This study indicated that supplementation with T3 at the dosage of 400 mg per day for 14 days did not induce haematoxicity and hepatotoxicity in subjects with metabolic syndrome