Piperine inhibits cytokine production by human peripheral blood mononuclear cells.

Piperine, an amide isolated from Piper species (Piperaceae), has been reported to exhibit central nervous system depression, anti-pyretic and anti-inflammatory activity. Immunomodulatory and anti-tumor activity of piperine has been demonstrated in mouse carcinomas. However, there is little information available concerning the effect of piperine on humans. We evaluated the immunopharmacological activity of this compound in human immune cells. Human peripheral blood mononuclear cells (PBMCs) were exposed to piperine, and cell proliferation was determined by the MTS assay. Piperine significantly inhibited phytohemagglutinin-stimulated human PBMC proliferation after exposure for 72 h. This compound inhibited PBMC activity, with an IC(50) of 100.73 ± 11.16 µg/mL. Production of interleukin-2 (IL-2) and interferon-γ (IFN-γ) was measured using an ELISA assay and RT-PCR. Piperine inhibited IL-2 and IFN-γ production in the PBMCs. RT-PCR data indicated that IL-2 and IFN-γ mRNA expression in PBMCs is suppressed by piperine. This compound significantly inhibited the production of these two cytokines by activated PBMCs in a dose-dependent manner. In conclusion, piperine appears to have potential as an immunomodulatory agent for immune system suppression.

Comparative pharmacokinetics and bioequivalence of two tablet formulations of 2 mg risperidone in healthy Thai male volunteers.

BACKGROUND: Risperidone is an atypical antipsychotic drug with potent serotonin and moderate dopamine antagonistic properties. It possesses good bioavailability following oral administration. Risperidone is primarily converted by the cytochrome P450 2D6 (CYP2D6) and 3A4 (CYP3A4) enzymes to 9-hydroxyrisperidone, its active metabolite with equivalent potency to the parent compound. OBJECTIVE: This study aimed to compare the pharmacokinetics and determine bioequivalence of two risperidone immediate release oral tablets, a test formulation (Risperidone GPO® or "Test") and a reference formulation (Risperdal® or "Reference"). METHOD: A single-dose, randomized, fasting, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in 23 healthy Thai male volunteers. Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 h following an oral administration of 2 mg risperidone. The plasma concentrations of risperidone and 9-hydroxyrisperidone were determined by using a validated HPLC method. Pharmacokinetic parameters of Test and Reference were obtained by noncompartmental analysis. RESULTS: The 90% confidence intervals for Test/Reference ratios of the pharmacokinetic parameters (Cmax, AUC0-t and AUC0-∞) of both risperidone and its active metabolite (9-hydroxyrisperidone) fell within the acceptable bioequivalence range (80 - 125%) according to ASEAN guideline. CONCLUSION: The two risperidone formulations are bioequivalent. The test formulation may be used for generic substitution where applicable.

Development of curcuminoids hydrogel patch using chitosan from various sources as controlled-release matrix.

In this study, we developed the hydrogel patch containing curcuminoids for application in cosmetic purpose. The powder of curcuminoids extracted from rhizome of Curcuma longa Linn. was first formulated into o/w microemulsions before incorporating into the polymer solution. The polymer solutions consisted of chitosan derived from various sources or the blended chitosan starch. We found that chitosan from squid pen gave the patch with highest strength and flexibility. After incorporation of curcuminoids microemulsion into the polymer solution of squid chitosan in ratio of 1 : 1 by weight, values of tensile strength and per cent elongation at break of the obtained patch decreased (from 4.55 +/- 0.41 N mm(-2) to 2.26 +/- 0.01 N mm(-2) for tensile strength and from 40.27 +/- 1.46% to 29.65 +/- 2.77% for elongation at break). The DSC thermogram of the squid patch containing curcuminoids implied non-crystalline structure of polymeric network, corresponding to porous characteristics of the patch surface. The results showed that the curcumin content remained at a concentration of 96% and 40% of the initial content after being kept at 4 degrees C and room temperature, respectively. When the patch was kept at 50 degrees C, the remaining curcumin could not be detected. According to vertical diffusion cell method, we found a rapid rate of curcumin release from the patch. The curcumin release pattern, which fitted well to the Higuchi's model, exhibited two distinct phases: the rapid phase (0-15 min), where the release rate of the curcumin averaged 0.74 microg min(-1) mm(-2), and the slow phase (15-120 min), where the release rate averaged 0.13 microg min(-1) mm(-2). Any sign of skin irritation was not observed in volunteers after single application of the curcuminoids patch in the under-eye area for 30 min. This finding indicates mildness to skin of the developed patch.