Biocompatible dendrimer for the solubility enhancement and sustained release of piroxicam

Piroxicam (PRM) a nonsteroidal anti-inflammatory medication is an oxicam-class used orally to treat gout, arthritis, and other inflammatory diseases. However, its poor aqueous solubility and bioavailability has hampered further clinical applications in health industries. This work emphasize on development of four types of functionalised biocompatible dendrimer with generation 0 and 1and examine its solubility, drug release and antibacterial activity. The maximum solubility enhancement of PRM up to 48 folds has been achieved by PAMAM (G1)-CH3 at a concentration of 9.9×10-4 M. The in vitro release gets sustained up to 450 mins for releasing 90% of drug from PAMAM (G1)-COCH3 compared to its parent dendrimer which is 120 min. The anti-bacterial studies reflected that when dendrimers are used as drug carriers, the inherent property of drug is not disturbed, instead the activity has been increased. The activity interms of zone of inhibition results in 1.5-2.0 folds increase and it is more pronounced in the case of B. subtilis rather than E.coli. This observation indicates evidence that dendrimer and their derivatives are promising candidates for drug solubility enhancer and effective delivery of drugs with drastic reduction in side effect and improved efficiency

Efficacy of an Extract of Ocimum tenuiflorum (OciBest) in the Management of General Stress: A Double-Blind, Placebo-Controlled Study

A randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy of OciBest, an extract of Ocimum tenuiflorum Linn. in symptomatic control of general stress. The participants received either placebo (n = 79) or OciBest (n = 71; 1200 mg of actives per day) for six weeks. The severity of stress-related symptoms was self-evaluated by patients at weeks 0, 2, 4 and 6 of the trial period using a symptom rating scale. After six weeks of intervention, scores of symptoms such as forgetfulness, sexual problems of recent origin, frequent feeling of exhaustion, and frequent sleep problems of recent origin decreased significantly (P ≤ 0.05) in OciBest group as compared with placebo group. Also, the total symptom scores of OciBest group revealed significant reduction (P ≤ 0.05) as compared to placebo group. The overall improvement in OciBest group was found to be 1.6 times or 39% more in the control of general stress symptoms with respect to placebo. No adverse events were reported during the study. The findings revealed that OciBest was found to be effective and well tolerated by all the patients over the six weeks of study period

Effect of rifampicin & isoniazid on the steady state pharmacokinetics of moxifloxacin.

BACKGROUND & OBJECTIVES Moxifloxacin (MFX) is reported to have promising antimycobacterial activity, and has a potential to shorten tuberculosis (TB) treatment. We undertook this study to examine the influence of rifampicin (RMP) and isoniazid (INH) on the steady state pharmacokinetics of MFX individually in healthy individuals. METHODS A baseline pharmacokinetic study of MFX (400 mg once daily) was conducted in 36 healthy adults and repeated after one week of daily MFX with either RMP (450/600 mg) (n = 18) or INH (300 mg) (n = 18). Plasma MFX concentrations were determined by a validated HPLC method. RESULTS Plasma peak concentration and exposure of MFX was significantly lower and plasma clearance significantly higher when combined with RMP (P<0.001). The C max to MIC and AUC 0-12 to MIC ratios of MFX were significantly lower during concomitant RMP (P<0.001). INH had no significant effect on the pharmacokinetics of MFX. INTERPRETATION & CONCLUSIONS Concomitant RMP administration caused a significant decrease in C max and AUC 0-12 of MFX, the mean decreases being 26 and 29 per cent, respectively. It is uncertain whether this decrease would affect the treatment efficacy of MFX. Prospective studies in TB patients are needed to correlate MFX pharmacokinetics with treatment outcomes

Efficacy of an Extract of Ocimum tenuiflorum (OciBest) in the Management of General Stress: A Double-Blind, Placebo-Controlled Study

A randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy of OciBest, an extract of Ocimum tenuiflorum Linn. in symptomatic control of general stress. The participants received either placebo (n = 79) or OciBest (n = 71; 1200 mg of actives per day) for six weeks. The severity of stress-related symptoms was self-evaluated by patients at weeks 0, 2, 4 and 6 of the trial period using a symptom rating scale. After six weeks of intervention, scores of symptoms such as forgetfulness, sexual problems of recent origin, frequent feeling of exhaustion, and frequent sleep problems of recent origin decreased significantly (P ≤ 0.05) in OciBest group as compared with placebo group. Also, the total symptom scores of OciBest group revealed significant reduction (P ≤ 0.05) as compared to placebo group. The overall improvement in OciBest group was found to be 1.6 times or 39% more in the control of general stress symptoms with respect to placebo. No adverse events were reported during the study. The findings revealed that OciBest was found to be effective and well tolerated by all the patients over the six weeks of study period

Biocompatible dendrimer for the solubility enhancement and sustained release of piroxicam

647-657Piroxicam (PRM) a nonsteroidal anti-inflammatory medication is an oxicam-class used orally to treat gout, arthritis, and other inflammatory diseases. However, its poor aqueous solubility and bioavailability has hampered further clinical applications in health industries. This work emphasize on development of four types of functionalised biocompatible dendrimer with generation 0 and 1and examine its solubility, drug release and antibacterial activity. The maximum solubility enhancement of PRM up to 48 folds has been achieved by PAMAM (G1)-CH3 at a concentration of 9.9×10-4 M. The in vitro release gets sustained up to 450 mins for releasing 90% of drug from PAMAM (G1)-COCH3 compared to its parent dendrimer which is 120 min. The anti-bacterial studies reflected that when dendrimers are used as drug carriers, the inherent property of drug is not disturbed, instead the activity has been increased. The activity interms of zone of inhibition results in 1.5-2.0 folds increase and it is more pronounced in the case of B. subtilis rather than E.coli. This observation indicates evidence that dendrimer and their derivatives are promising candidates for drug solubility enhancer and effective delivery of drugs with drastic reduction in side effect and improved efficiency

Chemistry of homo- and heterometallic bridged-borylene complexes

Thermolysis of [(Cp*RuCO)2B2H6] (1; Cp* = η5-C5Me5) with [Ru3(CO)12] yielded the trimetallaborane [(Cp*RuCO)3(μ3-H)BH] (2) and a number of homometallic boride clusters: [Cp*RuCO{Ru(CO)3}4B] (3), [(Cp*Ru)2{Ru2(CO)8}BH] (4), and [(Cp*Ru)2{Ru4(CO)12}BH] (5). Compound 2 is isoelectronic and isostructural with the triply bridged borylene compounds [(μ3-BH)(Cp*RuCO)2(μ-CO){Fe(CO)3}] (6) and [(μ3-BH)(Cp*RuCO)2(μ-H)(μ-CO){Mn(CO)3}] (7), where the [μ3-BH] moiety occupies the apical position. To test if compound 2 undergoes hydroboration reactions with alkynes, as observed with 6, we performed the reaction of 2 with the same set of alkynes under photolytic conditions. However, neither 2 nor 7 undergoes hydroboration to yield a vinyl–borylene complex. On the other hand, thermolysis of 6 with trimethylsilylethylene yielded the novel diruthenacarborane [1,1,7,7,7-(CO)5-2,3-(Cp*)2-μ-2,3-(CO)-μ3-1,2,3-(CO)-5-(SiMe3)-pileo-1,7,2,3,4,5-Fe2Ru2C2BH] (8). The solid-state X-ray diffraction results suggest that 8 exhibits a pentagonal -bipyramidal geometry with one additional CO capping one of its faces. Cluster 3 is a boride cluster where boron is in the interstitial position of a square-pyramidal geometry, whereas compound 4 can be described as a tetraruthenium boride in which the Ru4 butterfly skeleton has an interstitial boron atom. Electronic structure calculations of compound 2 employing density functional theory (DFT) generate geometries in agreement with the structure determinations. The existence of a large HOMO–LUMO gap in 2 is in agreement with its high stability. Bonding patterns in the structure have been analyzed on the grounds of DFT calculations. Furthermore, the B3LYP-computed 11B and 1H chemical shifts for compound 2 precisely follow the experimentally measured values. All the compounds have been characterized by IR and 1H, 11B, and 13C NMR spectroscopy, and the geometries of the structures were unambiguously established by crystallographic analyses of 2–4 and 8

Chemistry of Homo- and Heterometallic Bridged-Borylene Complexes

Thermolysis of [(Cp*RuCO)₂B₂H₆] (<b>1</b>; Cp* = η⁵-C₅Me₅) with [Ru₃(CO)₁₂] yielded the trimetallaborane [(Cp*RuCO)₃(μ₃-H)­BH] (<b>2</b>) and a number of homometallic boride clusters: [Cp*RuCO­{Ru­(CO)₃}₄B] (<b>3</b>), [(Cp*Ru)₂{Ru₂(CO)₈}­BH] (<b>4</b>), and [(Cp*Ru)₂{Ru₄(CO)₁₂}­BH] (<b>5</b>). Compound <b>2</b> is isoelectronic and isostructural with the triply bridged borylene compounds [(μ₃-BH)­(Cp*RuCO)₂(μ-CO)­{Fe­(CO)₃}] (<b>6</b>) and [(μ₃-BH)­(Cp*RuCO)₂(μ-H)­(μ-CO)­{Mn­(CO)₃}] (<b>7</b>), where the [μ₃-BH] moiety occupies the apical position. To test if compound <b>2</b> undergoes hydroboration reactions with alkynes, as observed with <b>6</b>, we performed the reaction of <b>2</b> with the same set of alkynes under photolytic conditions. However, neither <b>2</b> nor <b>7</b> undergoes hydroboration to yield a vinyl–borylene complex. On the other hand, thermolysis of <b>6</b> with trimethylsilylethylene yielded the novel diruthenacarborane [1,1,7,7,7-(CO)₅-2,3-(Cp*)₂-μ-2,3-(CO)-μ₃-1,2,3-(CO)-5-(SiMe₃)-<i>pileo</i>-1,7,2,3,4,5-Fe₂Ru₂C₂BH] (<b>8</b>). The solid-state X-ray diffraction results suggest that <b>8</b> exhibits a pentagonal -bipyramidal geometry with one additional CO capping one of its faces. Cluster <b>3</b> is a boride cluster where boron is in the interstitial position of a square-pyramidal geometry, whereas compound <b>4</b> can be described as a tetraruthenium boride in which the Ru₄ butterfly skeleton has an interstitial boron atom. Electronic structure calculations of compound <b>2</b> employing density functional theory (DFT) generate geometries in agreement with the structure determinations. The existence of a large HOMO–LUMO gap in <b>2</b> is in agreement with its high stability. Bonding patterns in the structure have been analyzed on the grounds of DFT calculations. Furthermore, the B3LYP-computed ¹¹B and ¹H chemical shifts for compound <b>2</b> precisely follow the experimentally measured values. All the compounds have been characterized by IR and ¹H, ¹¹B, and ¹³C NMR spectroscopy, and the geometries of the structures were unambiguously established by crystallographic analyses of <b>2</b>–<b>4</b> and <b>8</b>

Chemistry of Homo- and Heterometallic Bridged-Borylene Complexes

Thermolysis of [(Cp*RuCO)₂B₂H₆] (<b>1</b>; Cp* = η⁵-C₅Me₅) with [Ru₃(CO)₁₂] yielded the trimetallaborane [(Cp*RuCO)₃(μ₃-H)­BH] (<b>2</b>) and a number of homometallic boride clusters: [Cp*RuCO­{Ru­(CO)₃}₄B] (<b>3</b>), [(Cp*Ru)₂{Ru₂(CO)₈}­BH] (<b>4</b>), and [(Cp*Ru)₂{Ru₄(CO)₁₂}­BH] (<b>5</b>). Compound <b>2</b> is isoelectronic and isostructural with the triply bridged borylene compounds [(μ₃-BH)­(Cp*RuCO)₂(μ-CO)­{Fe­(CO)₃}] (<b>6</b>) and [(μ₃-BH)­(Cp*RuCO)₂(μ-H)­(μ-CO)­{Mn­(CO)₃}] (<b>7</b>), where the [μ₃-BH] moiety occupies the apical position. To test if compound <b>2</b> undergoes hydroboration reactions with alkynes, as observed with <b>6</b>, we performed the reaction of <b>2</b> with the same set of alkynes under photolytic conditions. However, neither <b>2</b> nor <b>7</b> undergoes hydroboration to yield a vinyl–borylene complex. On the other hand, thermolysis of <b>6</b> with trimethylsilylethylene yielded the novel diruthenacarborane [1,1,7,7,7-(CO)₅-2,3-(Cp*)₂-μ-2,3-(CO)-μ₃-1,2,3-(CO)-5-(SiMe₃)-<i>pileo</i>-1,7,2,3,4,5-Fe₂Ru₂C₂BH] (<b>8</b>). The solid-state X-ray diffraction results suggest that <b>8</b> exhibits a pentagonal -bipyramidal geometry with one additional CO capping one of its faces. Cluster <b>3</b> is a boride cluster where boron is in the interstitial position of a square-pyramidal geometry, whereas compound <b>4</b> can be described as a tetraruthenium boride in which the Ru₄ butterfly skeleton has an interstitial boron atom. Electronic structure calculations of compound <b>2</b> employing density functional theory (DFT) generate geometries in agreement with the structure determinations. The existence of a large HOMO–LUMO gap in <b>2</b> is in agreement with its high stability. Bonding patterns in the structure have been analyzed on the grounds of DFT calculations. Furthermore, the B3LYP-computed ¹¹B and ¹H chemical shifts for compound <b>2</b> precisely follow the experimentally measured values. All the compounds have been characterized by IR and ¹H, ¹¹B, and ¹³C NMR spectroscopy, and the geometries of the structures were unambiguously established by crystallographic analyses of <b>2</b>–<b>4</b> and <b>8</b>