Molecular encapsulation of thalidomide with sulfobutyl ether-7 beta-cyclodextrin for immediate release property: enhanced in vivo antitumor and antiangiogenesis efficacy in mice.

Thalidomide's reported ability to inhibit tumor angiogenesis has led to clinical trials determining its effectiveness in combating various types of cancer. Since thalidomide exhibits low oral bioavailability due to limitations in solubility, inclusion complexation using sulfobutyl ether-7 beta-cyclodextrin was used to improve the delivery of thalidomide. Our main goals were to increase the solubility, bioavailability as well as chemical stability of thalidomide through complexation with anionic beta-cyclodextrin, to characterize the complex in solid state using differential scanning calorimetry, X-ray powder diffractometry, and to explore thalidomide's antitumorigenic and antiangiogenesis potential when administered orally as free and in combination with cyclodextrin to experimental animals. The aqueous solubility and aqueous alkaline stability of thalidomide was markedly increased by the SBE7betaCD complexation. Thalidomide administered orally in combination with SBE7betaCD, led to a significant delay in tumor formation as a result of improved cellular drug absorption, distribution through solubilization in experimental animals. The improved pharmacological efficacy of the thalidomide-cyclodextrin complex compared to free thalidomide in mouse melanoma model suggest that such a delivery system may be useful for the improved therapeutics of thalidomide, in vivo.

Enhancement of dissolution profile by solid dispersion (kneading) technique.

This article investigates enhancement of the dissolution profile of valdecoxib using solid dispersion with PVP. The article also describes the preparation of fast-dissolving tablets of valdecoxib by using a high amount of superdisintegrants. A phase solubility method was used to evaluate the effect of various water-soluble polymers on aqueous solubility of valdecoxib. Polyvinyl pyrrolidone (PVP K-30) was selected and solid dispersions were prepared by the method of kneading. Dissolution studies using the USP paddle method were performed for solid dispersions of valdecoxib. Infrared (IR) spectroscopy, differential scanning calorimetry (DSC), and x-ray diffractometry (XRD) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on dissolution. Tablets were formulated containing solid dispersion products and compared with commercial products. IR spectroscopy, XRD, and DSC showed no change in the crystal structure of valdecoxib. Dissolution of valdecoxib improved significantly in solid dispersion products (< 85% in 5 minutes). Tablets containing solid dispersion exhibited better dissolution profile than commercial tablets. Thus, the solid dispersion technique can be successfully used for improvement of dissolution of valdecoxib.

Decreased B16F10 melanoma growth and impaired tumour vascularization in BDF1 mice with quercetin-cyclodextrin binary system.

The aim of this work was to study the inclusion behaviour of a poorly water-soluble bioflavonoid, quercetin, towards sulfobutyl ether-7beta-cyclodextrin. It also involves angiogenesis inhibition in-vivo in addition to in-vitro human cancer cell growth inhibition study of quercetin and its cyclodextrin complex. Drug-cyclodextrin solid inclusion complexes were prepared and characterized in solution and in the solid state. An in-vitro anti-proliferation study using plain drug and its solubilized form was carried out on human cancer cell lines of different origin. Further, an in-vivo tumour growth inhibition study was carried out using a mouse melanoma model. Histological sections of tumours were examined for the evaluation of tumour microvessel density. Significant enhancement of the solubility and dissolution rate of the quercetin, which occurred after complexation, might be attributed to the decrease in crystallinity of drug. SBE7betaCD complex of quercetin was more potent for inhibiting cell proliferation in human erythroleukaemia and cervix cancer cells. Decreased tumour microvessel density in mouse melanoma after oral quercetin administration led to diminished tumour cell proliferation. Quercetin-SBE7betaCD complex showed significantly improved anti-cancer activity at much lower concentration than the plain drug, providing evidence for dose reduction without affecting therapeutic efficacy when using cyclodextrin carriers.

Encapsulation of water-insoluble drug by a cross-linking technique: effect of process and formulation variables on encapsulation efficiency, particle size, and in vitro dissolution rate.

Ibuprofen-gelatin micropellets were prepared by the cross-linking technique using formaldehyde. Spherical micropellets having an entrapment efficiency of 65% to 85% were obtained. The effect of core to coat ratio, speed of agitation, temperature, and volume of oil phase was studied with respect to entrapment efficiency, micropellet size, and surface characteristics. Fourier transform infrared spectroscopy and differential scanning calorimetric analysis confirmed the absence of any drug-polymer interaction. X-ray diffraction patterns showed that there is a decrease in crystallinity of the drug. The micromeritic properties of micropellets were found to be slightly changed by changing various processing parameters to give micropellets of good flow property. The in vitro release profile could be altered significantly by changing various processing parameters to give a controlled release of drug from the micropellets. The stability studies of the drug-loaded micropellets showed that the drug was stable at storage conditions of room temperature, 37 degrees C, 25 degrees/60% relative humidity (RH) and 45 degrees/60% RH, for 12 weeks.