The anti-allergic drug, N-(3',4'-dimethoxycinnamonyl) anthranilic acid, exhibits potent anti-inflammatory and analgesic properties in arthritis.

OBJECTIVES: The degradation of tryptophan by indoleamine 2,3-dioxygenase yields a number of immunomodulatory metabolites, including 3-hydroxyanthranilic acid, 3-hydroxykynurenic acid and quinolinic acid. N-(3',4'-dimethoxycinnamonyl) anthranilic acid (3,4-DAA) is a synthetic anthranilic acid derivative that has been used therapeutically in Japan for many years as an anti-allergic drug and has recently been shown to be effective in a murine model of multiple sclerosis. METHODS: In the present study, we tested the efficacy of 3,4-DAA in collagen-induced arthritis, a mouse model of rheumatoid arthritis, and analysed its mechanism of action. RESULTS: Administration of 3,4-DAA after arthritis onset reduced clinical and histological severity of arthritis and reduced pain. It completely abrogated thermal and mechanical hyperalgesia. 3,4-DAA also suppressed Th1 cell activity in lymph node cell cultures and raised serum levels of IL-10. In vitro, 3,4-DAA suppressed IFNgamma production and proliferation of both T and B lymphocytes in a manner comparable with the endogenous tryptophan metabolite, 3-hydroxyanthranilic acid, suggesting similar mechanisms of action. CONCLUSION: It is concluded that 3,4-DAA has both anti-inflammatory and analgesic properties, and may therefore be useful in filling an unmet need, in the treatment of rheumatoid and other forms of arthritis, especially in the light of its analgesic properties.

Preformulation studies on Freund's incomplete adjuvant emulsion.

Freund's Incomplete Adjuvant (FIA), which is used in vaccine therapy, is a water-in-oil emulsion delivery system consisting of an aqueous internal phase containing an antigenic protein dispersed in an external phase containing a mixture of mannide monooleate and light mineral oil. Preformulation studies are reported in this investigation for FIA emulsion. The preformulation studies included the determination of the critical micelle concentration (CMC) of the formulations investigated, the surface activity of mannide monooleate at the interface between the oil phase and the aqueous phase containing ovalbumin as the model antigenic protein, and the effect of ovalbumin on the surface activity at the interface. The influence of the concentration of mannide monooleate and/or ovalbumin on the interfacial tension between light mineral oil and either purified water or 0.9% w/v normal saline solution was measured by the DuNouy Ring Method at 25 degrees C. The CMC was determined experimentally from the relationship between the concentration of the surface active agent in each formulation and the interfacial tension. The number of moles of the surface active agent per unit area at the interface (surface excess concentration) was calculated from the Gibbs' Adsorption equation. The results indicated that mannide monooleate was an effective surface active agent since the formulation containing only mannide monooleate provided the lowest magnitude of CMC. The presence of the surface active agent, mannide monooleate and/or ovalbumin, in the formulations studied reduced the interfacial tension between the two phases. The surface activity was influenced by the presence of an electrolyte (sodium chloride), a protein (ovalbumin), or mannide monooleate in the formulation. The presence of antigenic proteins in the aqueous phase of a waterin-oil emulsion influenced the effectiveness of a surface active agent in the formulation.

An in vitro method to investigate food effects on drug release from film-coated beads.

The influence of simulated high-fat meals on drug release from beads coated with modified-release ethylcellulose coating formulations was investigated as a function of plasticizer type and concentration, and coating level. Ethylcellulose-coated beads were soaked in peanut oil prior to testing to simulate the influence of concomitant administration of the dosage form with ingestion of fatty meals. The USP apparatus 3 dissolution procedure was employed to study the drug release properties of the beads. It was found that the ethylcellulose-coated beads plasticized with either triethyl citrate (TEC) or dibutyl sebacate (DBS) had faster drug release rates after the peanut oil treatment. Scanning electron microscopy (SEM) revealed that the peanut oil soak caused the polymeric films to detach from the surface of the bead, producing a series of uneven ridges and cracks in the coating. Modulated differential scanning calorimetry (DSC) demonstrated that the glass transition temperature was increased for DBS-plasticized films soaked in peanut oil, and that it was not influenced for TEC plasticized films. Similar results were found for the puncture strength, percent elongation, and modulus of elasticity for the DBS- and TEC-plasticized films soaked in peanut oil. The results verified that the DBS was solubilized and extracted from the plasticized film during the peanut oil soak, and that the film plasticized with the TEC was not significantly affected by the peanut oil soak. Drug release was influenced by the plasticizer type and concentration, and coating level applied to the beads.