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Modulation of the S1P1 receptor has been described to be an effective treatment of autoimmune diseases (eg, multiple sclerosis).

BackgroundRepaglinide is an oral hypoglycemic drug especially useful for the treatment of type 2 diabetes. This molecule has poor aqueous solubility, which is the rate-limiting step for absorption of the drug. Solubility can be increased by forming a complex with b-cyclodextrin because this molecule enhances the aqueous solubility of the drug through inclusion.PurposeThe aim of this work was to formulate a mouth-dissolving tablet of repaglinide-b-cyclodextrin complex, enhancing the bioavailability of the drug.Material and methodsRepaglinide and b-cyclodextrin were purchased from Sigma. Repaglinide and b-cyclodextrin were weighed accurately at 1:1, 2:1 and 3:1 molar ratios, mixed by trituration and sieved through a 0.25 micron sieve. A minimum volume of ethanol and water (1:1) was added. The tablets were prepared by the direct compression method using mycrocristalline cellulose, lactose and magnesium stearate. In vitro dissolution studies were performed using an apparatus with a rotating paddle (50 rpm) at 37°±0.2°C in a phosphate buffer (pH 6.8). At fixed time intervals, samples were withdrawn, filtered and spectrophotometrically assayed at 243 nm with a Perkin Elmer Lambda 45 UV-vis in a 10 mm quartz cell. Data was subjected to ANOVA followed by studentized range test using the software Statistica. A confidence limit of p<0.5 was fixed for the interpretation of results.ResultsThe inclusion efficency of different ratios of drug and b-cyclodextrin (1:1, 2:1 and 3:1) were calculated and results showed that the inclusion efficiency of 1:1 molar ratio complex was the highest. A dissolution study showed that the complex is more soluble than the drug.ConclusionThe main problem with repaglinide is poor bioavailability and its limited aqueous solubility. Results show that it is possible to enhance the dissolution rate and the bioavailability by preparing a complex with b-cyclodextrin and direct compression.References and/or acknowledgementsNo conflict of interest.

Phosphate (Pi) deficiency triggers the differential expression of a large set of genes, which communally adapt the plant to low Pi bioavailability. To infer functional modules in early transcriptional responses to Pi deficiency, we conducted time-course microarray experiments and subsequent coexpression-based clustering of Pi-responsive genes by pairwise comparison of genes against a customized database. Three major clusters, enriched in genes putatively functioning in transcriptional regulation, root hair formation, and developmental adaptations, were predicted from this analysis. Validation of gene expression by quantitative reverse transcription-PCR revealed that transcripts from randomly selected genes were robustly induced within the first hour after transfer to Pi-deplete medium. Pectin-related processes were among the earliest and most robust responses to Pi deficiency, indicating that cell wall alterations are critical in the early transcriptional response to Pi deficiency. Phenotypical analysis of homozygous mutants defective in the expression of genes from the root hair cluster revealed eight novel genes involved in Pi deficiency-induced root hair elongation. The plants responded rapidly to Pi deficiency by the induction of a subset of transcription factors, followed by a repression of genes involved in cell wall alterations. The combined results provide a novel, integrated view at a systems level of the root responses that acclimate Arabidopsis (Arabidopsis thaliana) to suboptimal Pi levels.

The term solid dispersion refers to a group of the solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug and matrix can be either crystalline or amorphous. The drug can be dispersed molecularly, in amorphous particles or in crystalline particles. Solid dispersion technologies are particularly promising for improving the aqueous solubility, dissolution rate and bioavailability of BCS Class II drugs as bioavailability of drugs depends on their solubility and permeability. The main objective of the present work was to evaluate the feasibility of the melt granulation technique to improve the dissolution characteristics of a poorly water soluble drug, Glibenclamide. Glibenclamide was chosen as a water-insoluble model drug. Conjugation of Glibenclamide with the different types of carriers was used to increase its Solubility and dissolution rate. Formulation of granules was done by physical mixture and melt granulation technique. The drug carrier interactions were studied by IR spectral analysis. Granules were evaluated by Bulk density, Tapped density, Carr’s index, Hausner ratio and Angle of repose. In-vitro dissolution studies were done on solid dispersion formulations.

Solubility is not to be confused with the ability to dissolve or liquefy a substance, since this process may occur not only because of dissolution but also because of a chemical reaction. Low aqueous solubility is the major problem encountered with formulation development of new chemical entities as well as for the generic development. Among all newly discovered chemical entities about 40% drugs are lipophilic and fail to reach therapeutic range due to their poor water solubility. Drug with poor water solubility cause slow dissolution rates, generally show erratic and incomplete absorption leading to low bioavailability when administered orally. This present review details about the different approaches used for the enhancement of the solubility of poorly water-soluble drugs include particle size reduction, nanonization, pH adjustment, solid dispersion, complexation, co-solvency, hydrotropy etc. The purpose of this article is to describe the techniques of solubilization for the attainment of effective absorption and improved bioavailability.