Effect of Argemone mexicana (L.) against lithium-pilocarpine induced status epilepticus and oxidative stress in Wistar rats.

Argemone mexicana (L.) has a role in the treatment of epileptic disorders in Indian traditional system of medicine. We studied its effect on induced status epilepticus (SE) and oxidative stress in rats. SE was induced in male albino rats by administration of pilocarpine (30 mg/kg, ip) 24 h after injection of lithium chloride (3 mEq/kg, ip). Different doses of the ethanol extract of A. mexicana were administered orally 1 h before the injection of pilocarpine. The severity of SE was observed and recorded every 15 min for 90 min and thereafter at every 30 min for another 90 min, using the Racine scoring system. In vivo lipid peroxidation of rat brain tissue was measured utilizing thiobarbiturate-reactive substances. Both in vitro free radical nitric oxide and 2,2-diphenyl-1-picryl hydrazyl scavenging activities of the extract were also determined. The SE severity was significantly reduced following oral administration of the extract at 250, 500 and 1000 mg/kg doses. None of the animals from groups 3 to 5 (with A. mexicana extract) have exhibited forelimb clonus of stage 4 seizure. The extract also exhibited both in vivo and in vitro antioxidant activities.

Assessment of hupu gum for its carrier property in the design and evaluation of solid mixtures of poorly water soluble drug - rofecoxib.

There are no reports about the pharmaceutical applications of hupu gum (HG). Hence the present study was undertaken to test its suitability in the dissolution enhancement of poorly water soluble drug. Rofecoxib (RFB) was taken as model drug. For comparison solid mixtures were prepared with carriers such as poly vinyl pyrrolidone (PVP), sodium starch glycollate (SSG) and guar gum (GG). Physical mixing (PM), co-grinding (CG), kneading (KT) and solvent evaporation (SE) techniques were used to prepare the solid mixtures, using all the carriers in different carrier and drug ratios. The solid mixtures were characterized by powder X-ray diffraction (XRD) and Fourier-transformed infrared spectroscopy (FTIR). There was a significant improvement in the dissolution rate of solid mixtures of HG, when compared with the solid mixtures of other carriers. There was an increase in dissolution rate with increase in concentration of HG upto 1:1 ratio of carrier and drug. No drug-carrier interaction was found by FTIR studies. XRD studies indicated reduction in crystallinity of the drug with increase in HG concentration. Hence HG could be a useful carrier for the dissolution enhancement of poorly water soluble drugs.

Bioavailability and pharmacokinetic studies of rofecoxib solid dispersion.

The present investigation deals with the determination of bioavailability of Rofecoxib solid dispersion compared to pure rofecoxib (RFB). The study of a non-blinded, open-label, crossover design was conducted in six healthy volunteers. Blood samples were collected for 12 h at specified intervals of time after the administration of formulations and analysed by suitable HPLC method. The pharmacokinetic parameters such as maximum plasma concentration (Cmax), time to reach (tmax), elimination rate constant (Kel) biological half-life (t1/2), absorption rate constant (Ka) and area under curve (AUC0-12 and AUC0-) were determined. Significant difference in the bioavailability of pure rofecoxib and solid mixture of rofecoxib prepared using hupu gum as carrier has been reported from the studies. The Peak plasma concentrations (Cmax) of 8.34 ng/mL at tmax of 4 h and Cmax of 76.84 ng/mL at tmax of 3 h were observed for RFB and solid mixture respectively. The results clearly indicated an enhancement in the bioavailability of rofecoxib in solid mixture preparation.

Assessment of effect of ethanolic extract of Tephrosia purpurea (L.) Pers., Fabaceae, activity on lithium-pilocarpine induced Status epilepticus and oxidative stress in Wistar rats / Avaliação do efeito do extrato etanólico da Tephrosia purpurea (L.) Pers., Fabaceae, sobre o status epilepticus induzido por lítio-pilocarpina e estresse oxidativo, em ratos Wistar

Tephrosia purpurea (L.) Pers., Fabaceae, is claimed to be of use in the control and treatment of a variety of epileptic disorders in Indian system of medicine. The present study plans to systematically evaluate T. purpurea and to verify this claim. Status epilepticus was induced in male albino rats of Wistar strain by administration of pilocarpine (30 mg/kg, i.p.) 24 h after lithium chloride (3 mEq/kg, i.p.). Different doses of the extract of T. purpurea were administered orally one hour before the injection of pilocarpine. The severity of status epilepticus was observed and recorded every 15 min till 90 min and thereafter every 30 min till 180 min, using the scoring system. The in vivo lipid peroxidation of rat brain tissue was measured. The in vitro NO free radical scavenging activity of plant extract was assessed. The interaction between plant extract and 2-diphenyl-2-picryl hydrazyl (DPPH) was also observed for in vitro free radical scavenging activity. The severity of status epilepticus was reduced with the administration of ethanolic extract of T. purpurea. Ethanolic extract of the plant exhibited both in vivo and in vitro antioxidant activity. The ethanolic extract of T. purpurea was found to be useful to control lithium-pilocarpine induced status epilepticus in albino rats of Wistar strain.

Tephrosia purpurea (L.) Pers., Fabaceae, é conhecida pelo seu uso no controle e tratamento de uma variedade de distúrbios epilépticos no sistema indiano de medicina. O presente estudo pretende avaliar de forma sistemática T. purpurea e verificar essa alegação. Status epilepticus foi induzido em ratos albinos machos da linhagem Wistar pela administração de pilocarpina (30 mg/kg, i.p.) 24 h após o cloreto de lítio (3 mEq/kg, i.p.). Diferentes doses do extrato de T. purpurea foram administrados por via oral uma hora antes da injeção de pilocarpina. A gravidade do status epilepticus foi observada e registrada a cada 15 min até 90 min e, posteriormente, a cada 30 min até 180 min, utilizando um sistema de pontuação. A peroxidação lipídica in vivo do tecido cerebral de ratos foi avaliada. A atividade captadora de radicais livres do extrato da planta foi avaliada in vitro. A interação entre o extrato da planta e 2-difenil-2-picril hidrazil (DPPH) também foi observada in vitro para atividade sequestradora de radicais livres. A gravidade do status epilepticus foi reduzida com a administração do extrato etanólico da T. purpurea. Extrato etanólico da planta apresentou, tanto in vivo quanto in vitro atividade antioxidante. O extrato etanólico da T. purpurea parece ser útil no controle de lítio de status epilepticus induzido pela pilocarpina em ratos albinos da linhagem Wistar.