High anti-inflammatory activity of harpagoside-enriched extracts obtained from solvent-modified super- and subcritical carbon dioxide extractions of the roots of Harpagophytum procumbens

Solvent-modified carbon dioxide extractions of the roots of Harpagophytum procumbens have been investigated with respect to extraction efficiency and content of harpagoside, and compared with a conventional extract. The effects of pressure, temperature, type and concentration of the modifier have been examined. Two extraction steps were necessary in order to achievehigh anti-inflammatory harpagoside-enriched extracts. The first extraction step was carried out in the supercritical state using carbon dioxide modified with n-propanol to remove undesired lipophilic substances. The main extraction was performed either in the supercritical or in the subcritical state with carbon dioxide modified with ethanol. The supercritical fluid extraction resulted in extracts containing up to 30% harpagoside. The subcritical extracts showed a harpagoside content of ca. 20%, but the extraction yield was nearly three times greater compared with supercritical conditions. The total harpagoside recovery resulting from the sum of the extract and the crude drug residue was greater than 99% in all experiments. The conventional extract and two carbon dioxide extracts were tested for in-vitro inhibition of 5-lipoxygenase or cyclooxygenase-2 biosynthesis. Both carbon dioxide extracts showed total inhibition on 5-lipoxygenase biosynthesis at a concentration of 51.8 mg/L. In contrast, the conventional extract failed to show any inhibition of 5-lipoxygenase biosynthesis.     

Inhibition of TNF-alpha synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract SteiHap 69.

Harpagophytum procumbens (Devil's Claw) is often used in the supportive treatment of inflammatory and degenerative diseases of the skeletal system. Here we studied the anti-inflammatory properties of the Harpagophytum extract SteiHap 69 (Steiner Harpagophytum procumbens extract 69) on primary human monocytes, a useful model of peripheral inflammation. After eliminating lipopolysaccharides of bacterial origin, SteiHap 69 prevented the LPS-induced synthesis of tumour necrosis factor alpha (TNFalpha) in stimulated primary human monocytes in a dose-dependent manner. Harpagide and harpagoside had no effect on LPS-induced TNFalpha-release. Our data provides evidence that the Harpagophytum extract SteiHap 69 has anti-inflammatory properties. Further studies are required in order to elucidate the molecular mechanism of Devil's claw anti-inflammatory effects.     

Granulation by Roller Compaction and Enteric Coated Tablet Formulation of the Extract of the Seeds of <Emphasis Type="BoldItalic">Glinus Lotoides</Emphasis> Loaded on Aeroperl® 300 Pharma

The purpose of this research was to improve the hygroscopicity and poor flow properties of the crude dry extract of the seeds of Glinus lotoides and improve the disintegration time of the core-tablets for enteric coated formulation thereof. The liquid crude extract of the plant was adsorbed on granulated colloidal silicon dioxide (Aeroperl 300 Pharma) at 30% w/w and the dry extract preparation (DEP) was dry-granulated with roller-compaction using Micro-Pactor. Hygroscopicity, flow property and disintegration time were improved significantly due to the adsorption and granulation processes. Moreover, the DEP does not become mucilaginous even at higher relative humidity levels (above 65%). Oblong tablets (20 x 8.25 mm) containing 947 mg of the granulated DEP (equivalent to the traditional dose), 363 mg of Avicel PH101 and 90 mg of Ac-di-Sol as disintegrant were formulated using an instrumented eccentric tablet machine at 20 kN. The tablets showed a crushing strength of 195 N, a friability of 0.4% and disintegrated within 9 min. The tablets were then enteric coated using polymethacrylate co-polymers (Eudragit L 100-55 and Kollicoat MAE 100P). The coated tablets resisted disintegration or softening in simulated gastric fluid for a minimum of 2 h and disintegrated within 15 min in intestine simulated fluid at pH 6.8. In addition to controlling the release of the active agents, the enteric coating improved the strength and decreased friability of the core-tablets.     

Preparative isolation and purification of harpagoside from Scrophularia ningpoensis hemsley by high-speed counter-current chromatography

The bioactive component harpagoside was successfully separated from the crude extract of Scrophularia ningpoensis Hemsley by one-step purification using high-speed counter-current chromatography (HSCCC). A two-phase solvent system containing n-butanol:ethyl acetate:water (1:9:10) was selected following consideration of the partition coefficient of the target compound. A 276 mg quantity of the crude extract was loaded onto a 250 mL HSCCC column and yielded 11 mg harpagoside at over 97% purity. The chemical structure of harpagoside was determined by HPLC-ESI/MS and 1H-NMR.     

Ibuprofen reduces the progression of permeability edema in an animal model of hyperdynamic sepsis

Since severity of acute lung injury (ALI) is reduced by pretreatment with non-steroidal agents, we hypothesized that ibuprofen would ameliorate ALI when administered after the onset of septic lung injury. Twenty-four hours after cecal ligation and perforation (CLP) in 23 sheep during a 4 h study period (period S), pulmonary lymph flow (QL) increased 16.2 +/- 12.1 ml/min (P less than 0.01) from base line, whereas lymph-to-plasma total protein concentration ratios ([L/P]TP) remained unchanged. During the subsequent 24 h of study (period D), 10 sheep received parenteral ibuprofen, 12.5 mg/kg every 6 h, and 13 sheep served as untreated septic controls. Throughout period D, a progressive increase in QL (16.2 +/- 16.3 ml/60 min) from period S was greater in the untreated than in the ibuprofen (2.5 +/- 9.0 ml/60 min, P less than 0.02) group. Between base line and period D, increase in lung wet-to-dry weight ratios was greater in the untreated group than in the ibuprofen group (P less than 0.05). Concurrently mean pulmonary arterial pressure increased 4.7 +/- 7.3 mmHg in the untreated group (P less than 0.05) during period D vs. 0.0 +/- 5.2 mmHg in the ibuprofen group (NS). When administered after septic ALI had been established by CLP, ibuprofen reduced an otherwise progressive increase in both fluid flux and extravascular lung water.     

The effects of Eucalyptus terpenes on hepatic cytochrome P450 CYP4A, peroxisomal Acyl CoA oxidase (AOX) and peroxisome proliferator activated receptor alpha (PPARalpha) in the common brush tail possum (Trichosurus vulpecula)

Eucalyptus leaves contain a high proportion of essential oils comprising of a complex mixture of monoterpenes such as 1,8-cineole, alpha-pinene, d-limonene and p-cymene. In this study, hepatic levels of microsomal lauric acid hydroxylase and peroxisomal cyanide-intensive palmitoyl coenzyme A oxidative activities were examined in livers of possums given an artificial diet consisting of the above monoterpenes for 10 days. These values were compared with those of possums fed a control diet containing only fruits and cereals. Peroxisomal cyanide-intensive palmitoyl coenzyme A oxidative activity was significantly higher in livers of treated possums relative to that of control possums (2.96+/-0.93 vs. 0.98+/-0.88 nmol/mg protein per min, P<0.01) (mean+/-S.D., n=4). A small increase in microsomal lauric acid hydroxylase activity was observed in the treated possum in comparison with the control group (4.40+/-0.85 vs. 3.60+/-0.48 nmol/mg protein per min) (mean+/-S.D., n=4). A higher NAD/ NADP ratio was observed in treated possums as compared with control possums (4.73+/-0.65 vs. 3.51+/-0.64 nmol/mg protein per min, P<0.05) (mean+/-S.D., n=4). No other statistically significant differences in pyridine nucleotide contents were found between control and treated possums. Northern blot analysis of mRNA from rat, human, terpene treated and control possum livers, using the corresponding koala cDNA probes, detected a more intense acyl CoA oxidase (AOX) mRNA band in livers of terpene fed possums. Negligible differences in the intensity of CYP4A and PPARalpha mRNA bands were observed between the two groups. These data suggest that Eucalyptus terpenes elevate hepatic AOX expression in possums.     

Development of a Melting Tablet Containing Promethazine HCl Against Motion Sickness

The purpose of this study was to design a 'Traveller Friendly Drug Delivery System' for PM-HCl. Conventional promethazine (PM-HCl) tablets are bitter, need to be taken 1 h before symptoms and water is also needed. Taste-masked granules were produced with Eudragit E100 by extrusion, and analyzed with FTIR, DSC, and XRD. Tablets formulated from granules by direct compression using Ac-Di-Sol, Polyplasdone-XL, Primojel and ion-exchanger Tulsion339 and evaluated for mass uniformity, friability, tensile strength, drug content uniformity, water absorption ratio, in-vitro and in-vivo disintegration time and in-vitro dissolution studies. The observed drug-polymer interactions and reduced crystallinity may be reasons for increased dissolution rates. The formulated tablets were disintegrated within 15 s. Tablets (25 mg PM-HCl) with Ac-Di-Sol (4%) showed complete release within 1 min, while marketed conventional tablets (Phenergan; Rhone-Poulec) release 25% during the same period. A preliminary stability studies for the prepared tablets carried at 30 +/- 2 degrees C/60 +/- 5% RH, and 40 +/- 2 degrees C/75 +/- 5%RH for 3 months showed no significant changes in the tablets quality at 30 +/- 2 degrees C/60 +/- 5% RH. However, at 40 +/- 2 degrees C/75 +/- 5%RH marked increase in in-vitro disintegration time, tensile strength and decrease in friability and water absorption ratio was found. The present studies indicate the abilities of Eudragit E 100 for taste masking and improving the dissolution profile of PM-HCl after complexation. In addition, by employing cost effective direct compression method, fast-dissolving tablets of 400 mg total weight with an acceptable quality could be prepared.     

Marked increase in gastric histidine decarboxylase activity in patients with hypergastrinemia.

Histidine decarboxylase (HDC) activity and histamine content were measured in endoscopic gastric biopsy specimens of 19 control subjects with normogastrinemia and 6 patients with hypergastrinemia. In controls, the HDC activity was 3 fold higher in fundic mucosa (120 +/- 13 fmol/min/mg protein, mean +/- S.E.) than in antral mucosa (39 +/- 5 fmol/min/mg protein). In patients with hypergastrinemia, an extremely high HDC activity (713 +/- 181 fmol/min/mg protein) was observed in fundic mucosa, although the HDC activity in antral mucosa was not significantly different from that of controls. The histamine content in fundic mucosa was also significantly higher in patients with hypergastrinemia than in controls but no significant difference was seen in histamine content in antral mucosa between the two groups. These results are compatible with the hypothesis that in man, as well as in rat, histamine synthesis in fundic mucosa is enhanced by gastrin.     

Iridoid glycosides from Harpagophytum procumbens D.C. (devil's claw)

Iridoid glycosides, harprocumbide A (6'-O-alpha-D-galactopyranosylharpagoside, 1) and harprocumbide B (6'-O-(cis-p-coumaroyl)-procumbide, 2) were isolated from the tubers of Harpagophytum prucumbens D.C., along with nine known iridoid glycosides 6-O-alpha-D-galactopyranosylharpagoside (3), and harpagoside (4), harpagide (5), 8-cinnamoylmyoporoside (6), 8-O-feruloylhapagide (7), procumbide (8), 6'-O-(p-coumaroyl)-procumbide (9), 8-O-(p-coumaroyl)-harpagide (10) and 8-O-(cis-p-coumaroyl)-harpagide (11). Compound 10 showed marginal inhibition activity against macrophages respiratory burst.     

Production of Iridoids and Phenolics by Transformed Harpagophytum procumbens Root Cultures

Harpagophytum procumbens (Devil's claw) is an important medicinal plant, which tubers are used for the treatment of different inflammatory diseases. In this study, the time courses of growth of Devil's claw hairy roots and accumulation of intracellular total iridoids and phenolics were investigated during cultivation under submerged conditions. After 21 days of growth in liquid hormone‐free MS medium, a growth index of 81.3 was achieved and the accumulated biomass reached 0.58 g/flask. It was found that the time courses of total iridoids and phenolics production showed almost the same patterns with a maximum on day 21 from the beginning of cultivation (15.93 mg harpagoside equivalents/L and 261 mg gallic acid equivalents/L, respectively). The methanolic extracts possessed relatively high DPPH‐radical scavenging properties (IC₅₀ 4.08 mg/mL), while for the culture media no antiradical activity was detected. According to our best knowledge, the present report is the first one dealing with the investigation of transformed root cultures from Harpagophytum procumbens plants.     

Purification and partial characterization of the b-type cytochrome from human polymorphonuclear leukocytes

Polymorphonuclear leukocytes contain an oxidase system that can be activated to produce superoxide radicals and hydrogen peroxide. A nonmitochondrial b cytochrome, functioning in the generation of these oxygen species, has been purified to apparent homogeneity from human polymorphonuclear phagocytes. After solubilization of the cytochrome with Triton X-100, the cell extract was subsequently chromatographed on Blue Sepharose and Sephacryl S-300. The final preparation was maximally purified 170-fold with a specific content of 5.33 +/- 2.03 nmol mg-1 of protein (mean +/- S.D.; n = 7) and a yield of 21 +/- 13% (n = 5). The apparent molecular mass of the nondenatured cytochrome was estimated by gel filtration to be 235 kDa. Upon polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, a single polypeptide was found with a molecular mass of 127 kDa. From the pyridine hemochrome spectrum 1 protoheme IX/polypeptide was calculated. The light absorbance bands of the dithionite-reduced cytochrome were found to be at 558.5 (alpha), 529 (beta), and 426 nm (Soret), and that of the oxidized cytochrome at 413.5 nm. The difference absorbance coefficients are delta epsilon (426.5 - 440 nm) = 160.6 +/- 11 mM-1 cm-1 and delta epsilon (558.5 - 542 nm) = 29.3 +/- 2 mM-1 cm-1 (mean +/- S.D.; n = 5). Carbon monoxide binds to the cytochrome in a time-dependent fashion (maximum binding after 50-60 min). The midpoint potential of the solubilized nonpurified cytochrome is identical to the cytochrome in situ (Em7.0 = -218 +/- 7 mV (mean +/- S.D.; n = 5)). However, purified cytochrome b shows a significantly decreased midpoint potential, estimated at -407 +/- 18 mV (n = 4). The protein does not contain noncovalently bound FAD or FMN, and no spectral evidence was obtained for the presence of covalently bound flavin. Preliminary amino acid analysis of the cytochrome shows a high content of hydrophilic residues.     

Radioimmunoassay of desglycinamide-arginine vasopressin and its application in a pharmacokinetic study in the rat

The purpose of this investigation was to develop a sensitive and selective radioimmunoassay for Desglycinamide-Arginine Vasopressin (DGAVP). DGAVP was extracted from rat plasma after protein precipitation, using Sep-Pak C18 cartridges and 50 mM glycine buffer/methanol (10:90) solution. Extraction recovery was 73 +/- 14% (mean +/- S.D.; n = 11) and good linearity was achieved in the concentration range of 0.25-128 pg/tube. Instantaneous tracer addition resulted in a detection limit of 250 fg/tube, whereas 24 hours preincubation and delayed tracer addition resulted in a detection limit of 100 fg/tube. Intra-assay variation ranged between 7.4% and 10.0% depending on the peptide concentration and inter-assay variation was 13.2%. Using this procedure, plasma pharmacokinetics of DGAVP in the rat were determined after IV administration. DGAVP plasma concentration showed a rapid distribution phase (t1/2 = 1.0 +/- 0.2 min) and a somewhat slower elimination phase (t1/2 = 7.2 +/- 2.1 min). High clearance values (CLss = 97 +/- 30 ml.min-1) suggest rapid metabolism by amino- and carboxy-peptidases.     

Osmotic regulation of prolactin secretion in the fetal sheep

The functions of prolactin in the fetus remain speculative. No obvious physiological role has been found for the prolactin present in the fetal or maternal plasma and amniotic fluid compartments. The aim of the present study was to investigate changes in fetal plasma prolactin following intracerebroventricular (i.c.r.) administration to the fetus of artificial cerebrospinal fluid of different tonicities. A lateral ventricle catheter was placed in 11 fetuses at 107-128 days of gestation. Either isotonic artificial cerebrospinal fluid (300 mOsm.1(-1);n = 9), 15% polyethylene glycol (340 mOsm.1(-1);n = 5), or 7% distilled water in isotonic artificial cerebrospinal fluid (270 mOsm.1(-1);n = 9) was infused i.c.v. at 35 mu1.min-1 for 240 min. At 180 min thyrotropin releasing hormone (TRH) was administered through a fetal a fetal jugular catheter. Fetal carotid arterial blood gases, plasma osmolality and concentrations of prolactin, vasopressin (AVP), and norepinephrine (NE) were measured. Administration of hypotonic artificial cerebrospinal fluid produced an increase in fetal plasma prolactin from 46.6 +/- 36 ng.ml-1 at 0 min to 83.3 +/- 49 ng.ml-1 at 180 min (mean +/- SEM; P less than 0.05). No changes in either AVP or NE were observed. Administration of hypertonic artificial cerebrospinal fluid produced a decrease in plasma prolactin from 85 +/- 57 at time 0 to 49 +/- 35 at 180 min (P less than 0.05). No changes in either AVP or NE were observed. Fetal plasma prolactin, AVP, and NE did not change during control infusion of isotonic artificial cerebrospinal fluid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Binding characteristics of [3H]17beta-estradiol in the hypothalamus of juvenile rainbow trout, Oncorhynchus mykiss

Gonadal steroids in the salmonid brain, acting through cellular receptors, may be responsible for the modulation of neuronal activity and organization of reproductive behaviors. We report our findings on the use of [3H]17beta-estradiol (E2) to identify intracellular estrogen receptors (ERs) in the hypothalamus of juvenile rainbow trout, Oncorhynchus mykiss. Specific binding (B(SP)) of [3H]E2 was tissue dependent between 0.5 and 2.25 hypothalamus equivalents for cytosol and nuclear extract preparations, respectively. B(SP) in cytosol fractions increased with time and reached maximum levels (4.18 nM) at 2.5 h incubation; by contrast, B(SP) in nuclear extract increased with time to achieve maximum levels (3.9 nM) by 2 h incubation. The association rate constants (k(+1)) for cytosol and nuclear extract preparations were 1.10 +/- 0.02 x 10(8) M(-1) min(-1) and 1.27 +/- 0.04 x 10(8) M(-1) min(-1), respectively. Equilibrium bound B(SP) dissociated from cytosol preparations with a half life (t1-2) of 42 min and a dissociation rate constant (k(-1)) of 1.01 +/- 0.03 min(-1). B(SP) dissociated from nuclear extract preparations with a t1-2 = 45 min and k(-1)= 0.92 +/- 0.01 min(-1) x B(SP) was saturable in both extract preparations with a calculated equilibrium dissociation constant (Kd) of 1.46 +/- 0.1 nM (cytosol) and 2.37 +/- 0.2 nM (nuclear), and a maximum number of binding sites (B(MAX)) of 50.85 +/- 3.2 fmol mg(-1) protein and 61.74 +/- 2.65 fmol mg(-1) protein, respectively. In both preparations, B(SP) was differentially displaced by structurally similar compounds with a rank order of potency of E2 > estrone > estriol > 17alpha-ethynyl estradiol > testosterone > progesterone = tamoxifen > cortisol > dexamethasone > > beta-sitosterol. These properties of specifically bound [3H]E2 suggest the presence of an ER in the hypothalamus of juvenile rainbow trout comparable with ERs identified in salmonid liver.     

Postischemic reperfusion of the spinal cord: prolonged reperfusion alleviates the metabolic alterations induced by 25 min ischemia in the cervical and thoracolumbal segments.

In recent years, increasing amount of information has indicated that in some tissues the main damage due to oxidative stress does not occur during reperfusion but during the ischemic episode of the ischemia/reperfusion event. In this respect, serious doubts were also expressed about the origin of the increased amounts of free radicals which were believed to form and reported to appear in the perfusate during the first minutes of reperfusion. Moreover, speculative explanations were only available for a second increase in lipid peroxidation which was reported to occur after postischemic reperfusions exceeding 60 min. For this reasons, the present paper reports the results of investigation of ischemia/reperfusion injury to the cervical (CE) and thoracolumbal (ThL) segments of the spinal cord (SP) after an acute 25 min occlusion of the abdominal aorta, followed by 60-120 min reperfusion of the ischemic areas in rabbits. In CE and ThL segments of the SP, the ischemia induced: 1) a decrease in activities of superoxide dismutase (SOD), from 57.35+/-6.36 to 45.27+/-5.45 U x mg(-1) x min(-1) (S.E.M., 20.92%), p < 0.01, and from 58.36+/-5.45 to 33.00+/-4.55 U x mg(-1) x min(-1) (S.E.M., 43.46%), p < 0.001; 2) a significant decrease in gamma-glutamyl transpeptidase (gamma-GTP), from 114.66+/-1.45 to 99.88+/-4.4 micromol p-nitroaniline x mg(-1) x h(-1) (S.E.M. 12.89 %), p < 0.05 and from 112.24+/-1.20 to 95.09+/-2.40 micromol p-nitroaniline x mg(-1) x h(-1) (S.E.M., 16.26%), p < 0.05; 3) a considerable depression in Na,K-ATPase activity, from 7.14+/-0.58 to 5.08+/-0.32 micromol Pi x mg(-1) x h(-1) (S.E.M., 28.86%), p < 0.01, and from 7.23+/-0.11 to 5.09+/-0.31 micromol Pi x mg(-1) x h(-1) (S.E.M., 30.00%), p < 0.01. The Na,K-ATPase activity became decreased by ischemia and remained depressed significantly (all p < 0.01) throughout the experiment. After 60 min of reperfusion, SOD activity in the CE segment and that of gamma-GTP in the CE as well as ThL segments recovered, even slightly surpassing the control values, wheras SOD activity in the ThL segment became stabilized again close to its post-ischemic value. Prolonged, reperfusion for 120 min resulted in a further increase in gamma-GTP activity in the CE and ThL segments (to 132.79 and 132.30%, p < 0.01), and this was accompanied by a slight (p > 0.05) elevation in the content of conjugated dienes as well as by a new wave of depression of the SOD activity (p < 0.05) in both the CE and the ThL segment. From our results it could be concluded that all considerable damage to the spinal cord occurred during the ischemic period. In the period of reperfusion reparative changes started to predominate. This is in accordance with the recent discoveries indicating that, when coupled with an increase in tissue gamma-GTP activity, the post-ischemic reparative changes comprise a replenishment of the cell glutathione pool. This process is accompanied with a gradual increase in H2O2 production that results in repeatead inhibition of the SOD activity and a tendency to conjugated dienes formation.     

Capture and immobilization of wild brown palm civets in Western Ghats

A mixture of 15 mg/kg body weight ketamine hydrochloride (KE) and 1.5 mg/kg body weight xylazine hydrochloride (XY) was used to successfully immobilize free-ranging brown palm civets (Paradoxurus jerdoni). Between March 1998 and June 1999, 10 immobilizations of 7 individuals were carried out in tropical rainforests of the Kalakad-Mundanthurai Tiger Reserve (India). Five males and two females were captured in Havahart live traps, using banana as bait. The mean dosage for the animals, whose weight (mean +/- SD) was 2.4 kg +/- 0.8 was 36.0 +/- 11.0 mg KE and 3.7 +/- 1.1 mg XY, administered intramuscularly. Mean time for lateral recumbency was 6.1 +/- 3.78 min (n = 10) and the mean time taken for complete recovery was 84.9 +/- 28.8 min (n = 9). Recovery was gradual and no fatalities or injuries occurred during the operation. The drug combination used was effective and has the potential for immobilizing other viverrids.     

Evidence for a role of hyaluronan in the spacing of fibrils within collagen bundles in rabbit synovium

Synovial hydraulic resistance is vital for the retention of intra-articular fluid, and originates within the matrix of biopolymers in the intercellular gaps. Specific digestion of hyaluronan resulted in a increase in synovial hydraulic permeability from 0.478+/-0.24 microl min(-1) cm H(2)O(-1) in control tissue to 4.561+/-0.40 microl min(-1) cm H(2)O(-1) (mean+/-S.D., n=6 rabbits, P<0.001 t test). To investigate whether hyaluronidase also altered the interstitial ultrastructure, morphometry of hyaluronidase treated synovium was carried out. The most striking novel finding was that hyaluronidase treatment reduced extrafibrillar volume fraction within the synovial collagen bundles from 50.5+/-11.1% to 36.8+/-15.5% (mean+/-S.D., n=6 rabbits, P<0.001, two-way anova). This was accompanied by a reduction in interfibrillar centre to centre spacing from 101+/-11 (control) to 84+/-6 nm (mean+/-S.D.; n=6 rabbits, P<0.001) in enzyme-treated bundles. Individual fibrils showed a small but highly significant reduction in cross-sectional diameter from 76.9+/-6.3 to 72.5+/-6.3 nm (mean+/-S.E.; P<0.001) after hyaluronidase treatment. The findings indicate that hyaluronan chains have a major organisational role within the collagen bundle itself. The trans-synovial pathway comprises bundles and substantial areas of intervening, bundle-free matrix, and it is possible that bundle collapse contributes to a rise in overall permeability by increasing the inter-bundle space.     

Preparation and In-vivo Pharmacokinetic Study of a Novel Extended Release Compression Coated Tablets of Fenoterol Hydrobromide

The aim of this study was to formulate extended release compression coated core tablets of fenoterol hydrobromide, a selective beta(2) adrenergic receptor agonist, in an attempt to prevent nocturnal asthma. Two hydrophilic polymers viz Kollidon SR, Polyox WSR 303 and a hydrophobic one (Precirol ATO5) were employed. Compression coated tablets were formulated by preparing a core tablet containing 7.5 mg drug and various amounts of polymer and Emcompress then compressed coated with the same polymeric materials. For comparison purpose different matrix tablets were also prepared employing the same polymers. In-vitro release studies were carried out at different pH (1.2 and 6.8). Pharmacokinetics of extended release tablets as well as commercially available immediate release tablets (Berotec) were studied after oral administration to beagle dogs using a new developed LC-MS/MS method with a lower limit of quantification of 1 ng/ml. Fenoterol release from compression coated tablets was significantly lower than matrix tablets. The mechanism of release was changed with the nature and content of polymer. The release pattern of drug from F16 containing 40 mg Kollidon SR divided in the core tablet (15 mg) and the rest in the compressed coat (25 mg) showed a typical zero order release kinetic that could extend drug release >10 h and reasonable time for 75% to be released (t(75)) (8.92 h). When compared to immediate release Berotec tablet the MRT was significantly extended from 7.03 +/- 0.76 to 10.93 +/- 1.25 h (P < 0.001) and HVD(t 50%Cmax) was also significantly extended from 2.71 +/- 0.68 to 6.81 +/- 0.67 h with expected prevention of nocturnal asthma.     

Harpagoside: from Kalahari Desert to pharmacy shelf

Harpagoside is an iridoid glycoside that was first isolated from Harpagophytum procumbens (devil’s claw, Pedaliaceae), a medicinal plant in which it is the major constituent of the iridoid pool. Both the pure compound and devil’s claw extracts have potent anti-rheumatic, anti-inflammatory and analgesic effects. According to the European Pharmacopoeia commercial devil’s claw products should contain at least 1.2% harpagoside. However, the compound has also been isolated from several other plant species and in vitro plant culture systems. Recent advances in knowledge of harpagoside distribution, biosynthesis/accumulation and pharmacology are summarized in this review. We also discuss the possible synergism and/or antagonism between major constituents in harpagoside-containing phytopharmaceutical products. Finally, future perspectives for its potential application are highlighted.