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Pharmacokinetic Study of Nanoparticulate Curcumin: Oral Formulation for Enhanced Bioavailability  [PDF]
R. Ravichandran
Journal of Biomaterials and Nanobiotechnology (JBNB) , 2013, DOI: 10.4236/jbnb.2013.43037

Curcumin, a bioactive component of turmeric, which is a commonly used spice and nutritional supplement, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). In recent years, the potential pharmacological actions of Curcumin in inflammatory disorders, cardiovascular disease, cancer, Alzheimer’s disease and neurological disorders have been shown. However, the clinical application of Curcumin is severely limited by its main drawbacks such as instability, low solubility, poor bioavailability and rapid metabolism. Multifarious nanotechnology-based drug delivery systems for Curcumin including liposomes, polymeric nanoparticles, solid lipid nanoparticles, micelles, nanogels, nanoemulsions, complexes and dendrimer/dimer, have been attempted to enhance the oral bioavailability, biological activity or tissue-targeting ability of Curcumin. We attempted the nanosuspensions based delivery of curcumin. Nanonisation renders curcumin completely dispersible in aqueous media. To enhance the curcumin absorption by oral administration, nanoparticulate solid oral formulation of curcumin was prepared by us and the resulting capsule was then examined for its efficiency on bioavailability in Male Wistar rats at a dose of 100 mg curcumin/kg body weight and the pharmacokinetic parameters were compared to those of normal curcumin powder and a commercial curcumin capsule CUR-500. The bio-distribution of curcumin in organs of rat was also studied. Nanoparticulation significantly raised the curcumin concentration in selective organs in the body. The results obtained provide promising results for nanoparticulate Curcumin to improve its biological activities. Enhanced bioavailability of curcumin in the form of nanoparticle is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease. The available information also strongly suggests that nano-formulation of ingredients such as curcumin may be used as a novel nutrient delivery system too.

Role of surfactant and pH in dissolution of curcumin  [cached]
Rahman SMH,Telny T,Ravi T,Kuppusamy S
Indian Journal of Pharmaceutical Sciences , 2009,
Abstract: Curcumin is a phytoconstituent with wide range of biological activity. It is poorly soluble in water. In the present study a new dissolution medium was developed, as there is no validated dissolution method available in the literature. The composition of the dissolution medium was selected on the basis of solubility data at 37°. Solubility data revealed that addition of surfactant may be suitable as a dissolution medium. The suitability of dissolution medium (0.5% sodium lauryl sulphate in water) relative to the other dissolution medium was evaluated. The selected dissolution media was used for the evaluation of curcumin tablets.
Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells
Wang K, Zhang T, Liu L, Wang XL, Wu P, Chen ZG, Ni C, Zhang JS, Hu FQ, Huang J
International Journal of Nanomedicine , 2012, DOI: http://dx.doi.org/10.2147/IJN.S34702
Abstract: vel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells Original Research (2629) Total Article Views Authors: Wang K, Zhang T, Liu L, Wang XL, Wu P, Chen ZG, Ni C, Zhang JS, Hu FQ, Huang J Published Date August 2012 Volume 2012:7 Pages 4487 - 4497 DOI: http://dx.doi.org/10.2147/IJN.S34702 Received: 06 June 2012 Accepted: 27 June 2012 Published: 13 August 2012 Ke Wang,1 Tao Zhang,1 Lina Liu,2 Xiaolei Wang,1 Ping Wu,1 Zhigang Chen,1 Chao Ni,1 Junshu Zhang,1 Fuqiang Hu,4 Jian Huang1,3 1Cancer Institute, 2Department of Pharmacy, Second Affiliated Hospital (Binjiang Branch), 3Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, 4College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China Background and methods: Curcumin has extraordinary anticancer properties but has limited use due to its insolubility in water and instability, which leads to low systemic bioavailability. We have developed a novel nanoparticulate formulation of curcumin encapsulated in stearic acid-g-chitosan oligosaccharide (CSO-SA) polymeric micelles to overcome these hurdles. Results: The synthesized CSO-SA copolymer was able to self-assemble to form nanoscale micelles in aqueous medium. The mean diameter of the curcumin-loaded CSO-SA micelles was 114.7 nm and their mean surface potential was 18.5 mV. Curcumin-loaded CSO-SA micelles showed excellent internalization ability that increased curcumin accumulation in cancer cells. Curcumin-loaded CSO-SA micelles also had potent antiproliferative effects on primary colorectal cancer cells in vitro, resulting in about 6-fold greater inhibition compared with cells treated with a solution containing an equivalent concentration of free curcumin. Intravenous administration of curcumin-loaded CSO-SA micelles marginally suppressed tumor growth but did not increase cytotoxicity to mice, as confirmed by no change in body weight. Most importantly, curcumin-loaded CSO-SA micelles were effective for inhibiting subpopulations of CD44+/CD24+ cells (putative colorectal cancer stem cell markers) both in vitro and in vivo. Conclusion: The present study identifies an effective and safe means of using curcumin-loaded CSO-SA micelles for cancer therapy.
Dissolution of Curcumin Microencapsulation Coated by Chitosan-Alginate-Glutaraldehide
Herdini,Latifah K. Darusman,Purwantiningsih Sugita
Makara Seri Sains , 2010,
Abstract: In vitro dissolution of curcumin coated by chitosan-alginate gel in its optimum condition was studied. The maceration process using 17.08% ethanol yields and the content of the curcumin in the extract detected by visible spectrophotometry 430 nm is found to be 10.30%. its optimum condition was obtained using response surface method at concentration was fixed (1.75% [b/v]). The dissolution assay was done at 37 C, at 100 rpm of stirring rate in 8 hours. Aliquots were taken at 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360, 420, 480 minutes. Absorbance of the Aliquots was measured at 430 nm. The curcumin released has the best linear correlation to the first order reaction with releasesd constant, k = 2.24 10-3 minute-1 while it’s half live is t1/2 = 5.16 hours. Release curcumin was determined mainly by diffusion mechanism. Compared to the result based on Fick model, the one of Higuchi model is better in agreement in reproducing the released data.
Formulation and Dissolution Study of Valsartan Immediate Release Tablets
B. Brahmaiah*, K. Sasikanth, Sreekanth Nama , P.Suresh, Patan Adam Khan
Indian Journal of Pharmaceutical and Biological Research , 2013,
Abstract: In the present study, design of oral immediate release tablets of Valsartan by direct compression techniquewas carried out. The main aim and objective of the work is to formulate immediate release tablets usingdifferent direct compression vehicles (DCV’S) in different ratios. The main motive is to compare thedissolution profile of these formulations and conclude the best formulation which release drug at a fasterrate. To determine the best fit dissolution profile for the dosage forms. Valsartan tablets were formulated byusing microcrystalline cellulose (diluents), potato starch, acacia (binder) and magnesium stearate(lubricant). The granules were compressed into tablets and were subjected to dissolution studies. Thedissolution profile of the formulation F2 was found to have better dissolution rate compared to others. TheIn-vitro dissolution studies of all the formulations were conducted and the results were obtained, it wasconcluded that formulation F2 was the best with fast release of drug compared to others.
Neha Parmar et al
International Journal of Pharmaceutical Sciences and Research , 2012,
Abstract: The present work aim was “Formulation Strategy for Dissolution Enhancement of Simvastatin”. Simvastatin is lipid lowering drug which is known as HMG CoA reductase. The objective of this study was to increase the solubility of poorly water soluble drug, namely simvastatin, by the formation of solid dispersion and complex and also using the microwave induction technique on these formations. For solid dispersion method dispersion carrier used were poloxamer 407 and gelucire 44/14. The fusion method was used to prepare the dispersions. For inclusion complexation method β-cyclodextrin derivative of cyclodextrin was used to prepare complex with drug. Kneading method was used for formulation. After completion of these two techniques these polymers were used for the microwave induced fusion method. All the ratio of drug and polymer were used to heat for different time interval. These samples were used for solubility measurement. In the solid dispersion technique, simvastatin show higher increase in solubility with gelucire 44/14 in the ratio of 1:5 as compare to poloxamer 407. In the microwave induced fusion method simvastatin show higher solubility with simvastatin with gelucire 44/14 after 10 mins time interval as compare to poloxamer 407 and β-cyclodextrin. Solubility of simvastatin increased higher with gelucire 44/14 by using microwave induced fusion method as compare to other technique. By using gelucire 44/14 with simvastatin it show 94% increase in solubility of simvastatin as compare to pure drug in water.
Improved solubilization of curcumin with a microemulsification formulation  [PDF]
Annals of the University Dunarea de Jos of Galati. Fascicle VI : Food Technology , 2011,
Abstract: Due to the large number of bioactive substances, with low and very low solubility in water, new and improved investigation methods were developed. Researches in this area have shown that lipid systems in lipophilic substances formulation increase their bioavailability and prevent or reduce the toxicological risk because most of the components involved in the formulation are of natural origin, with a structure compatible with biological membranes components. Among the lipid systems used in the leaching, transport and release of lipophilic substances there are: liposomes, solid lipid nanoparticles, double and single emulsions, autoemulsionante and auto-microemulsionante lipid systems. The last are the subject of the present research and meet specialists in concern for the harmonization of cost-benefit-risk in order to improve population health. Curcumin [(1E, 6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is a yellow pigment derived from the rhizome of the plant Curcuma Longa with phenol groups and conjugated double bounds which is unstable at light and basic pH, degrading within 30 minutes. The aim of this study is curcumin solubilization used as alimentary dye in automicroemulsionante systems. Dye/oil/surfactant/cosurfactant mixing ratio was made, based on quaternary phase diagrams. Mesofazice structures were revealed by conductivity and viscosimetric analysis. A curcumin solubilization system in aqueous medium was obtained. On the other hand, this paper studies the colour evolution of these automicroemulsionante systems comparing with hexane dye solution. The use of the chromatic attributes L*, a* and b* and L*, C* and hab, suggested by the Commission Internationale de l’Eclairage (CIE) (i.e., the CIELAB system), obtained from direct transmitance measurements, which made it possible to follow the evolution of colour.
V.A. Kekre et al
International Journal of Pharmaceutical Sciences and Research , 2012,
Abstract: The simple, accurate and precise HPTLC method was developed for quantification of curcumin content in dietary supplement formulation. In this method, individual curcuminoids (curcumin, demethoxy curcumin and bisdemethoxy curcumin) with piperine were resolved using mobile phase n-hexane: ethyl acetate: methanol: formic acid (8: 2: 1: 2-3 drops v/v) on a plate precoated with silica gel 60 F254 and quantified densitometrically in absorbance mode at 421 nm. The Rf value of curcumin was found to be 0.29. Linearity for curcumin was established between concentration range of 100-180 ng/spot with correlation coefficient of 0.999. The method was further validated as per ICH guidelines. The LOD and LOQ values for curcumin were found to be 27.3 ng and 82.7 ng respectively. The results of percent recovery and repeatability studies with standard deviation (≤2%), concluded that the developed method was accurate and precise and can be used for routine analysis of curcumin in dietary supplement formulations.
Dr. G. Nageswara Rao et al
International Journal of Pharmaceutical Sciences and Research , 2012,
Abstract: Salbutamol is a potent anti-asthmatic agent, is a short-acting β2-adrenergic receptor agonist act. In the present study, an attempt has been made to prepare fast dissolving tablets of Salbutamol in the oral cavity with enhanced dissolution rate and to achieve better patient compliance. The tablets were prepared with four superdisintegrants e.g., Sodium starch glycolate, Cross-povidone, Cross-carmellose sodium, Pregelatinized starch by direct compression method. The pre-compression parameters of mixed blend were examined for angle of repose, bulk density, tapped density, Compressibility index and Hausner’s ratio. The tablets were evaluated for hardness, friability, weight variation, disintegration time, dissolution rate, content uniformity and drug content. It was concluded that the fast dissolving tablets with proper hardness, rapidly disintegrate with enhanced dissolution can be made using selected superdisintegrants. Among all formulations, batch D4 was considered as best since it showed enhanced dissolution, which leads to improved bioavailability, improved effectiveness and hence better patient compliance.
Studies on formulation and in vitro dissolution of Embelin tablets  [cached]
Patel R,Pundarikakshudu K,Momin Munira,Patel M
Indian Journal of Pharmaceutical Sciences , 2006,
Abstract: The objective of the present study was to develop a tablet formulation of embelin employing the wet granulation and direct compression techniques. This study was also carried out to design a suitable dissolution medium for embelin. Effect of different diluents like lactose, microcrystalline cellulose, and co-crystallized lactose-microcrystalline cellulose were studied for improving the flow and compressibility. Binders such as starch paste and alcoholic polyvinyl pyrrolidone were used to optimize the crushing strength of the formulation. Dried starch powder was used as a disintegrating agent in both techniques. Pre and post formulation parameters were studied for all the batches. Co-crystallized lactose-microcrystalline cellulose and alcoholic polyvinyl pyrrolidone proved to be the best diluent and binder respectively. Solubility study of embelin in different media revealed that embelin has optimum solubility in phosphate buffer of pH 8 and in 2% aqueous sodium lauryl sulfate solution. Incorporation of 10% v/v ethanol in phosphate buffer of pH 7.4, significantly increased the solubility of embelin. These solutions were also found to be the most suitable media for dissolution of embelin in dissolution studies.
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