Bioavailability studies on guar gum-based three-layer matrix tablets of trimetazidine dihydrochloride in human volunteers.

Guar gum-based three-layer matrix tablets of a highly water-soluble drug, trimetazidine dihydrochloride, were evaluated for their in vivo release in healthy volunteers in comparison with commercially available conventional immediate release tablets. Six healthy volunteers participated in the study and a two-way crossover design was followed. The plasma concentration of trimetazidine dihydrochloride was estimated by reverse-phase HPLC. The pharmacokinetic parameters were calculated from the plasma concentration of trimetazidine dihydrochloride versus time data. The delayed T(max), decreased C(max) and K(a), unaltered bioavailability, and prolonged t(1/2) and MRT indicated a slow and prolonged release of trimetazidine dihydrochloride from guar gum three-layer matrix tablets in comparison with the immediate release tablet dosage form. The guar gum three-layer matrix tablets of trimetazidine dihydrochloride may be useful in providing constant drug delivery with minimum fluctuations.     

路路通内酯的化学结构

用红外,质谱,¹H,¹³CNMR和¹H-¹³CCOLOC等光谱解析,确定了新化合物路路通内酯的结构为3-羰基-11α,12α-环氧-13β-氧-齐墩果-28β-酸-13,28-γ-内酯,命名为路路通内酯。     

Pharmacokinetic evaluation of guar gum-based three-layer matrix tablets for oral controlled delivery of highly soluble metoprolol tartrate as a model drug.

The objective of the present study is to carry out pharmacokinetic evaluation of oral controlled release formulation (guar gum-based three-layer matrix tablets) containing highly soluble metoprolol tartrate as a model drug. Six healthy volunteers participated in the study, and a two-way crossover design was followed. The plasma concentration of metoprolol tartrate was estimated by reverse-phase HPLC. The pharmacokinetic parameters were calculated from the plasma concentration of metoprolol tartrate versus time data. The delayed T(max) lower C(max) decreased K(a) unaltered bioavailability and prolonged t(1/2) indicated a slow and prolonged release of metoprolol tartrate from guar gum three-layer matrix tablets in comparison with the immediate release tablet dosage form. The results of the study indicated that guar gum three-layer matrix tablets were able to provide oral controlled delivery of highly water-soluble drug such as metoprolol tartrate in humans.     

Improved biorefinery pathways of marine diatoms using a water miscible ionic liquid and its colloidal solution: efficient lipid extraction and in situ synthesis of fluorescent carbon dots for bio-imaging applications

In this study, a water-miscible ‘classic’ ionic liquid (IL), 1-ethyl-3-methylimidazoliumacetate ([EMIM][Ac]), has been used for lipid extraction from marine diatoms Thalassiosira lundiana CSIR-CSMCRI 001 by following a non-polar solvent partition method. The composition of lipid was determined using gas chromatography-mass spectrometry (GC-MS). In total, 91.4 mg g⁻¹ (dry wt) of lipid was produced, out of which the percentage of docosahexaenoic acids (DHA), myristic acid, palmitic acid, and arachidonic acid was 19.6%, 15.1%, 11.2%, and 10.4%, respectively. The IL-inseparable residual waste solution was directly used to generate green fluorescent carbon dots (FCDs) by constructing a colloidal solution with the help of a surface-active IL, choline dioctyl sulfosuccinate ([Cho][AOT]). The stability of colloidal FCDs was examined using FTIR, FT-NMR, and Raman spectroscopy. FCDs were extracted from the colloidal solutions via the demicellization process and characterized using HR-TEM (2 to 5 nm) and PXRD techniques. The optical properties of colloidal FCDs were measured using UV-Vis and fluorescence spectroscopy and showed a wide range of emission (λ_{460 nm} to λ_{590 nm}). Such FCD stabilized colloidal solutions could be effectively used in fluorescence imaging of yeast cells, thus making the biorefinery approach more sustainable.

In this study, a water-miscible ionic liquid (IL), 1-ethyl-3-methylimidazoliumacetate ([EMIM][Ac]), has been used for lipid extraction from marine diatoms Thalassiosira lundiana CSIR-CSMCRI 001 by following a non-polar solvent partition method.     

Studies on the development of colon-targeted delivery systems for celecoxib in the prevention of colorectal cancer

The nonsteroidal anti-inflammatory drugs (NSAIDs) are found to be potential chemopreventive agents of colorectal cancer. Celecoxib, an NSAID with selective cyclooxygenase-2 inhibition, was proved to be effective for the prevention of colon cancer in patients with familial adenomatous polyposis (FAP) and sporadic polyps. In the light of this information, the present study was carried out to develop oral colon-targeting drug delivery systems for celecoxib using guar gum as a carrier. Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The tablets were evaluated for hardness, drug content and were subjected to in vitro drug release studies. The amount of celecoxib released from the matrix tablets at different time intervals was estimated by a HPLC method. Guar gum matrix tablets released only 2-4% of celecoxib in the physiological environment of stomach and small intestine depending on the proportion of guar gum used in the formulation. When the dissolution study was continued in simulated colonic fluids (rat caecal content medium), the matrix tablets containing 20% of guar gum released another 37% of celecoxib after degradation by the colonic bacterial action. The matrix tablets containing 30% of guar gum released about 24% of celecoxib in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that the matrix tablets containing either 20 or 30% of guar gum are most likely to target celecoxib for local action in the colon. The guar gum matrix tablets of celecoxib showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 degrees C/RH 75% for 6 months. Differential scanning calorimetry (DSC) studies indicated no possibility of interaction between celecoxib and guar gum/other formulation excipients.     

Prevalence and aetiology of neurological impairment in extremely low birthweight infants

Objective : To determine the prevalence and perinatal predictors of cerebral palsy, intellectual impairment, visual impairment and deafness in a cohort of extremely low birthweight (ELBW) infants at two years of age.
Methodology : The study population comprised 199 of the 224 (89%) ELBW infants managed at the Mater's Mothers Hospital, Brisbane, between July 1977 and February 1990 and who survived to two years. The prevalence of cerebral palsy, intellectual impairment, blindness and deafness was measured by clinical, psychometric and audiological assessment and the association with 24 risk factors examined.
Results : Cerebral palsy occurred in 20 children (10%). Risk of cerebral palsy was associated with ventricular dilatation, intraventricular haemorrhage, necrotizing enterocolitis and multiple birth, though only ventricular dilatation (OR 4.41; 95% Cl 1.32-14.8) remained significant in the adjusted analysis. Intellectual impairment occurred in 20 children (10%) and was independently associated with ventricular dilatation (OR 15.0; 95% Cl 2.2-102.8), ventilation F _iO₂ >80% (OR 3.4; 95% Cl 1.01-11.5), vaginal delivery (OR 3.5; 95% Cl 1.09-11.4) and male sex (OR 6.1; 95% Cl 1.67-22.3). No perinatal predictor was statistically associated with risk of deafness. Retinopathy of prematurity (OR 36.9; 95% Cl 2.8-495.5) was associated with risk of later visual impairment.
Conclusions : Intellectual impairment was associated with a broad range of perinatal variables. Cerebral palsy was associated with fewer variables, all of which were also associated with intellectual impairment. Neurologic injury was associated with male sex and multiple birth, which are not biological insults themselves, but may be markers of susceptibility to injury.     

Formulation of an HPMC gel drug reservoir system with ethanol-water as a solvent system and limonene as a penetration enhancer for enhancing in vitro transdermal delivery of nicorandil

The objective of the present study was to formulate a hydroxypropyl methylcellulose (HPMC) gel drug reservoir system with ethanol-water as a solvent system and limonene as a penetration enhancer for enhancing the transdermal delivery of nicorandil so as to develop and fabricate a membrane-moderated transdermal therapeutic system (TTS). The in vitro permeation of nicorandil was determined across rat abdominal skin from a solvent system consisting of ethanol or various proportions of ethanol and water. The ethanol-water (70:30 v/v) solvent system that provided an optimal transdermal permeation was used in formulating an HPMC gel drug reservoir system with selected concentrations (0% w/w, 4% w/w, 6% w/w, 8% w/w or 10% w/w) of limonene as a penetration enhancer for further enhancement of transdermal permeation of nicorandil. The amount of nicorandil permeated in 24 h was found increased with an increase in the concentration of limonene in the drug reservoir system up to a concentration of 6% w/w, but beyond this concentration there was no further increase in the amount of drug permeated. The flux of nicorandil was 370.9 +/- 4.2 microg/cm2 x h from the drug reservoir system with 6% w/w of limonene, which is about 2.6 times the required flux to be obtained across rat abdominal skin for producing the desired plasma concentration for the predetermined period in humans. The results of a Fourier Transform Infrared study indicated that limonene enhanced the percutaneous permeation of nicorandil by partially extracting the stratum corneum lipids. It is concluded that the HPMC gel drug reservoir system prepared with a 70:30 v/v ethanol-water solvent system containing 6% w/w of limonene is useful in designing and fabricating a membrane-moderated TTS of nicorandil.     

Pharmacokinetic evaluation of guar gum-based colon-targeted drug delivery systems of tinidazole in healthy human volunteers

The aim of the present investigation was to determine the in vivo availability of guar gum-based colon-targeted tablets of tinidazole in comparison with immediate release tablets of tinidazole in human volunteers. Six healthy volunteers participated in the study, and a cross-over design was used. The plasma concentration of tinidazole was estimated by HPLC. The pharmacokinetic parameters were calculated from the plasma concentration of tinidazole versus time data. The immediate release tablets of tinidazole produced a peak plasma concentration (C_max of 3239 ± 428 ng/ml) at 1.04 ± 0.32 hr (T_max), whereas colon-targeted tablets produced peak plasma concentration (C_max of 2158 ± 78 ng/ml) at 14.9 ± 1.6 hr. The delayed T_max, decreased C_max, and K_a, and unaltered bioavailability and elimination half-life of tinidazole from guar gum-based colon-targeted tinidazole tablets, in comparison with the immediate tablets, indicated that the drug was not released in the stomach and small intestine but delivered to the colon. Slow absorption of the drug from the less absorptive colon might result in the availability of the drug for local action in the colon. The guar gum-based colon-targeted tablets of tinidazole may be useful in providing an effective and safe therapy of intestinal amoebiasis.     

Adsorption of nickel on flyash in natural and acid treated forms

Studies on removal of Ni2+ by adsorption on flyash and acid treated flyash have been carried out at room temperature (30+/-1 degrees C). The adsorption isotherm of Ni2+ on flyash and acid treated flyash was obtained in a batch reactor. Various parameters such as pH, initial concentration of adsorbate and adsorbent dose were studied. The experimental adsorption data fitted reasonably well to Langmuir, Freundlich and Redlich - Peterson isotherms for both the adsorbents. The adsorption follows Lagergren first order kinetic model. The monolayer adsorption model are found to be 41.7 and 62.9 mg/g respectively. Acid treated flyash has been observed to have greater adsorptive capacity than flyash in natural form.