RESUMEN
Carbamoylethyl pullulan-grafted palmitic acid (CP-g-PA), a novel self-assembled polymer was synthesized and examined for its efficacy in delivering the raloxifene (RA) to mammary carcinoma. The synthesized CP-g-PA was confirmed by evaluating through various spectral and morphological attributes. Further, the central composite design-response surface methodology with two factors at three levels was utilized to obtain the optimized and stable polymeric micelles. The optimized formulation was subjected to in vitro and in vivo evaluation. RA loaded polymeric micelles (RA-PMs) were spherical in shape with particle size less than 100 nm and high entrapment efficiency (77.02%). The developed formulation exhibited pH-dependent release profile of RA when loaded in polymeric micelles and provides substantial compatibility to erythrocytes. In vivo pharmacokinetic study demonstrates that RA-PMs offers higher mean residence time and volume of distribution as compared to pure RA. Besides, the biodistribution study manifested enhanced drug concentration in tumor and decreased concentration in other tissue as compared to pure drug. The treatment with RA-PMs also increases the median survival time, tumor inhibition rate and % increase in life span of the tumor bearing rats. Overall, the results pointed towards the overwhelming response of RA when loaded into micelles made from CP-g-PA.
Asunto(s)
Antineoplásicos , Micelas , Animales , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Portadores de Fármacos , Estudios de Factibilidad , Glucanos , Ácido Palmítico , Tamaño de la Partícula , Polímeros , Clorhidrato de Raloxifeno , Ratas , Distribución TisularRESUMEN
The present investigation entails the synthesis of smart pullulan polymeric micelles for evaluating its tumor targeting potential. For this purpose, two step polymerization synthesis reactions were conducted. In the first step, carbamoylethylation occurs by reaction of the free alcoholic moieties at 6th position of glucopyranose unit of pullulan with acrylamide in presence of alkali to obtain carbamoylethyl pullulan (CmP). In the second step, CmP undergoes graft polymerization with stearic acid (SA) to obtain CmP-g-stearic acid diblock co-polymer (CmP-g-SA) as evident from FTIR and NMR analysis. The XpRD spectra showed crystalline nature that was further confirmed by SEM indicating rough and poly-porous morphology. The QbD based optimized formulations of raloxifene HCl (RLX) loaded polymeric micelles (RLX PMs) exhibited pH-dependent release profile with added advantage of 1.2 times reduction in percentage hemolysis giving substantial compatibility with erythrocytes. In vivo pharmacokinetic performance of RLX PMs suggested enhanced mean residence time and volume of distribution. Besides, the biodistribution study of RLX PMs manifested enhanced entry of RLX in mammary carcinoma tissues as compared to normal tissues suggested that CmP-g-SA based micelles enhanced the anti-tumor activity of RLX. Overall, the findings pointed toward the biocompatibility of CmP-g-SA as a potential carrier system for the delivery of RLX.
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Micelas , Neoplasias , Humanos , Glucanos , Neoplasias/tratamiento farmacológico , Polímeros , Clorhidrato de Raloxifeno/química , Ácidos Esteáricos , Distribución TisularRESUMEN
The current endeavor was aimed to fabricate spray dried Nelfinavir Mesylate particles (SDNPs) that upon reconstitution with body fluids releases amorphous Nelfinavir Mesylate with enhanced oral bioavailability. For this purpose, feed mixture was prepared containing solubilized NFM, solid substrate and solvent system. The NFM was solubilized in a mixture of Maisine 35-1 (200 mg), Tween80 (500 mg) and Transcutol HP (300 mg). Three different solid substrates with high specific surface area were used: Neusilin® UFL2, (magnesium aluminometasilicate), Aerosil 200® (colloidal silica) and Syloid 244 FP® (porous silicon dioxide). Central composite design-response surface methodology (CCD-RSM) with three-factor (two numeric and one categorical) at three-level was used to select the appropriate solid substrate and to develop optimized SDNPs. The solid characterization by scanning electron microscopy, differential scanning calorimetry and powder X-ray diffraction studies indicated the absence of crystalline NFM in the formulations. The drug distribution analysis using raman spectroscopy suggested uniform distribution of amorphous NFM in optimized SDNPs-1 formulation. The transmission electron microscopy revealed the spherical structure of reconstituted SDNPs that releases amorphous NFM with globules size less than 110 nm. The solid substrate had significant and positive effect in drug dissolution; the mean dissolution time of NFM loaded in SDNPs was considerably improved. The bioavailability study resulted in enhanced magnitude of Cmax and AUC for SDNPs. The tissue distribution studies exhibited significantly higher brain and lymph nodes distribution as compared to putative form. Overall, the results pointed towards the overwhelming response of the SDNPs to be used for HIV treatment.
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Química Farmacéutica/métodos , Desecación , Nelfinavir/administración & dosificación , Administración Oral , Animales , Disponibilidad Biológica , Rastreo Diferencial de Calorimetría , Liberación de Fármacos , Excipientes/química , Masculino , Nelfinavir/farmacocinética , Análisis Numérico Asistido por Computador , Tamaño de la Partícula , Ratas Wistar , Medición de Riesgo , Espectrometría Raman , Distribución TisularRESUMEN
The current investigation entails systematic development of EFV (Efavirenz) loaded isotropic mixture prepared with long chain triglycerides for obliterating food associated variability and minimizing the erratic absorption behavior. For this purpose, the optimized isotropic mixture (EF1) consists of Maisine 35-1 (20%), Transcutol HP (17.7% w/w) and Cremophor RH 40:Labrasol (1:1) (62.3% w/w) was formulated by employing D-optimal mixture design that after numerical optimization showed highest desirability of 0.995. Further, the dissolution behavior of EFV suspension in biorelevant dissolution media's simulate the fed and fasted small intestine conditions, clearly anticipated that there is an influence of food effect for EFV. However, when EFV loaded into isotropic mixture, the food effect was abolished and no significant difference was seen in biorelevant dissolution media's. The tissue distribution of EFV from EF1 follows order: blood plasmaâ¯>â¯heartâ¯>â¯brainâ¯>â¯lymph nodesâ¯>â¯liver. Interestingly, the in-vivo animal pharmacokinetic performance showed positive food effect after administration of EFV suspension and marketed formulation. However, the developed formulation (EF1) nullifies this food effect. In nutshell, these studies suggested significant enhancement in the biopharmaceutical attributes of a stable and robust EFV loaded isotropic mixture.
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Benzoxazinas/administración & dosificación , Interacciones Alimento-Droga , Lípidos/química , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Administración Oral , Alquinos , Animales , Benzoxazinas/química , Benzoxazinas/farmacocinética , Ciclopropanos , Sistemas de Liberación de Medicamentos , Absorción Intestinal , Masculino , Conejos , Ratas , Ratas Wistar , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/farmacocinética , Distribución TisularRESUMEN
The main hurdle in the oral delivery of cinnarizine is its supersaturation, precipitation and re-dissolution process, influencing the oral bioavailability. To overcome this problem, an attempt was made to develop immediate and prolong buoyant tablet of cinnarizine. For this purpose, polyacrylamide-g-corn fibre gum (p-CFG) was synthesized as mucoadhesive cum swellable polymer and it was compared with already used HPMC K4M polymer. The central composite design with two numeric and one categorical factor was choosen to optimize conc. of p-CFG (X1), concentration of NaHCO3 (X2) and type of effervescent agents (X3). The bioadhesive strength of p-CFG tablet was 2.4 times higher than HPMC K4M containing tablet. The formulation composition comprises of p-CFG (64.3%), sodium bicarbonate (12.9%) and citric acid (2%) (FCNZ) fulfilled the maximum requirement of an optimized formulation. The in-vivo animal pharmacokinetic performance revealed larger plasma half-life and reduced elimination rate as compared to CNZ suspension. Interestingly, the absorption of CNZ from optimized formulation was 3 times enhanced than from CNZ suspension. Overall, the enhancement in the oral bioavailability of CNZ was evident that is due to its prolonged gastric residence time. Furthermore, the swelling associated floating followed by mucoadhesive nature of tablet was observed by X-ray imaging studies.
Asunto(s)
Resinas Acrílicas/química , Cinarizina/farmacología , Gomas de Plantas/química , Zea mays/química , Animales , Cinarizina/sangre , Cinarizina/farmacocinética , Excipientes , Procesamiento de Imagen Asistido por Computador , Análisis Numérico Asistido por Computador , Conejos , Radiografía Abdominal , Espectroscopía Infrarroja por Transformada de Fourier , Sus scrofa , Comprimidos , Agua/química , Rayos XRESUMEN
The present study was aimed at exploiting the wound healing applications and tablet coating potential of Tamarindus indica pectin-chitosan (PCH) conjugate for reducing recovery period from TNBS induced colitis. The PCH (60:40, 3% w/v) solution when spray coated followed by drying at 50°C created hydrophobic surface, that may be due to interaction of pectin with chitosan as evident from temperature ramping rheological investigations. Further, the 15% w/v coating was sufficient to prevent Mesalamine (Ma) release in pH 1.2. The AUC and AUMC of PCH coated tablets were 1.98 and 17.69 fold increased as compared to uncoated tablets. A synergistic therapeutic effect of PCH conjugate with Ma was evident from the colon/body weight ratio, clinical activity and damage score. Overall, the findings suggested PCH and Ma (20mg) reduces the recovery period from 5 to 4days with reduction in dose.
Asunto(s)
Quitosano/administración & dosificación , Colitis/tratamiento farmacológico , Pectinas/administración & dosificación , Exudados de Plantas/administración & dosificación , Animales , Quitosano/química , Colitis/inducido químicamente , Modelos Animales de Enfermedad , Sistemas de Liberación de Medicamentos , Humanos , Pectinas/química , Exudados de Plantas/química , Ratas , Comprimidos/administración & dosificación , Comprimidos/química , Tamarindus/química , Ácido Trinitrobencenosulfónico/toxicidad , Cicatrización de Heridas/efectos de los fármacosRESUMEN
BACKGROUND: The study was aimed to enhance the mucoadhesive potential of Eudragit RS 100 and RL 100 using iron oxide. METHODS: Microspheres of Eudragit RS/RL100, containing cinnarizine, were prepared by emulsification solvent evaporation technique employing 32 full factorial design. Eudragit RS or RL (X1) and iron oxide (X2) concentrations were the independent variables. Particle size, entrapment efficiency, mucoadhesion, zeta potential and t90% were the response variables. Microspheres when characterized by FTIR-ATR and DSC confirm entrapment of drug. RESULTS: SEM analysis of microspheres exhibits roughness/micropores responsible for drug release. Particle size of Eudragit RS and Eudragit RL microspheres was found to increase from 275.60±2.68 to 438.72±22.73 nm and 283.14±1.95 to 475.55±29.66 nm. Incorporation of iron oxide increases zeta potential from 0.88±0.18 to 10.74±1.78 mV and 1.12±0.11 to 14.44±2.44 mV for Eudragit RS and RL microspheres, respectively. Highest mucoadhesion and zeta potential were obtained when 4.5% w/v of X1 and 20% w/v of X2 were used in the formulation of microspheres. CONCLUSION: The r2 values were significantly higher (P < 0.01) for the Langmuir equation as compared to Freundlich equation, indicating the involvement of electrostatic forces in the specific adsorption of mucin on to Eudragit microspheres. In vivo study indicates 2.5 to 3 times increased bioavailabity of cinnarizine through mucoadhesive microspheres.
Asunto(s)
Resinas Acrílicas/química , Cinarizina/química , Diseño de Fármacos , Compuestos Férricos/química , Microesferas , Polímeros/química , Resinas Acrílicas/metabolismo , Resinas Acrílicas/farmacocinética , Adsorción , Animales , Disponibilidad Biológica , Cinarizina/sangre , Cinarizina/farmacocinética , Femenino , Masculino , Mucinas/química , Tamaño de la Partícula , Polímeros/metabolismo , Polímeros/farmacocinética , Conejos , Propiedades de SuperficieRESUMEN
The aim of present investigation was to utilize quality by design approach for the synthesis of polyacrylamide corn fibre gum (PAAm-g-CFG) from corn fibre gum (CFG) by varying concentration of acrylamide and initiator. The spectral analysis (ATR-FTIR, 1H NMR, DSC, X-ray and Mass spectroscopy) was conducted to assure grafting copolymerization of CFG with acrylamide. The powder flow properties confirm the porous nature of PAAm-g-CFG. The grafted copolymer dispersion showed shear thinning behaviour that follows Herschel Bulkley model. The viscoelastic analysis suggested viscous liquid like nature of PAAm-g-CFG and its viscosity increases with increase in concentration of PAAm-g-CFG. The mucoadhesive strength of synthesized PAAm-g-CFG was found to be higher than moringa oleifera gum, karaya gum, guar gum, xanthan gum, chitosan and gelatin. Further, the results pointed toward enhanced thermal stability of PAAm-g-CFG. Thus, PAAm-g-CFG has a great potential to be used in food and pharmaceutical industry.
Asunto(s)
Resinas Acrílicas , Gomas de Plantas/química , Zea mays/química , ViscosidadRESUMEN
Poor aqueous solubility and moderate permeability of Nelfinavir mesylate (NFM) leads to high variability in absorption after oral administration. To improve the solubility and bioavailability of NFM, the self microemulsifying drug delivery system (SMEDDS) was developed. For this purpose, Quality by design (QbD) approach employing D-optimal mixture design was used to prepare SMEDDS of NFM. Further, the software generated numerically optimized SMEDDS were developed by utilizing desirability function. Maisine 35-1, Tween 80, and Transcutol HP were identified as oil, surfactant, and co-surfactant that had best solubility for NFM. Ternary phase diagrams were plotted to identify the self-emulsification region. Dissolution of putative NFM in simulated fasted or fed small intestinal conditions, respectively, predicted that there is a positive food effect. However, NFM loaded SMEDDS showed absence of food effect with no significant difference in dissolution performance either in Fasted or fed state simulated intestinal fluid (FaSSIF or FeSSIF) biorelevent dissolution media. The prepared SMEDDS were thermodynamically stable with droplet size (121 nm), poly dispersity index (PDI) (0.198) and emulsification time (<1 min). Transmission electron microscopy (TEM) analysis confirmed the spherical shape of the reconstituted SMEDDS droplets. The ex vivo performance revealed 4.57 fold enhancement in the apparent permeability of NFM as compared to NFM suspension. The animal pharmacokinetic analysis in New Zealand strain rabbits indicated food effect on pure NFM suspension. However, absence of food effect and 3.5-3.6 fold enhancement in the oral bioavailability was observed when NFM was formulated into SMEDDS. Thus, it could be envisaged that development of SMEDDS formulation of NFM could be one of the best alternative to enhance oral bioavailability of NFM.
Asunto(s)
Sistemas de Liberación de Medicamentos , Nelfinavir/administración & dosificación , Animales , Disponibilidad Biológica , Química Farmacéutica , Emulsiones , Glicoles de Etileno/administración & dosificación , Glicoles de Etileno/química , Ayuno/metabolismo , Interacciones Alimento-Droga , Tracto Gastrointestinal/metabolismo , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/sangre , Inhibidores de la Proteasa del VIH/química , Inhibidores de la Proteasa del VIH/farmacocinética , Absorción Intestinal/efectos de los fármacos , Ácidos Linoleicos/administración & dosificación , Ácidos Linoleicos/química , Masculino , Nelfinavir/sangre , Nelfinavir/química , Nelfinavir/farmacocinética , Permeabilidad/efectos de los fármacos , Polisorbatos/administración & dosificación , Polisorbatos/química , Conejos , Ratas , Solubilidad , Tensoactivos/administración & dosificación , Tensoactivos/químicaRESUMEN
The present investigation was aimed to prepare orally disintegrating films (ODFs) containing aprepitant (APT), an antiemetic drug employing pullulan as film forming agent, tamarind pectin as wetting agent and liquid glucose as plasticizer and solubiliser. The ODFs were prepared using solvent casting method. The method was optimized employing 3(2) full factorial design considering proportion of pullulan: tamarind pectin and concentration of liquid glucose as independent variables and disintegration time, wetting time, folding endurance, tensile strength and extensibility as dependent variables. The optimized ODF was evaluated for various physicochemical, mechanical, drug release kinetics and bioavailability studies. The results suggested prepared film has uniform film surface, non-sticky and disintegrated within 18s. The in-vitro release kinetics revealed more than 87% aprepitant was released from optimized ODF as compared to 85%, 49%, and 12% aprepitant release from marketed formulation Aprecap, micronized aprepitant and non micronized aprepitant, respectively. The results of animal preference study indicated that developed aprepitant loaded ODFs are accepted by rabbits as food material. Animal pharmacokinetic (PK) study showed 1.80, 1.56 and 1.36 fold enhancement in relative bioavailability for aprepitant loaded ODF, Aprecap and micronized aprepitant respectively, in comparison with non-micronized aprepitant. Overall, the solubilised aprepitant when incorporated in the form of aprepitant loaded ODF showed enhanced bioavailability as compared to micronized/non-micronized aprepitant based oral formulations. These findings suggested that aprepitant loaded ODF could be effective for antiemesis during cancer chemotherapy.
Asunto(s)
Antieméticos/administración & dosificación , Portadores de Fármacos/administración & dosificación , Morfolinas/administración & dosificación , Administración Oral , Animales , Antieméticos/química , Antieméticos/farmacocinética , Aprepitant , Química Farmacéutica , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberación de Fármacos , Glucosa/química , Cinética , Masculino , Morfolinas/química , Morfolinas/farmacocinética , Pectinas/química , Conejos , Solubilidad , Gusto , Resistencia a la TracciónRESUMEN
The present investigation was aimed at development of silicate corn fiber gum (SCFG) particles as superior solid carrier for the preparation of Aprepitant (APT)-loaded self-emulsifying powder (SEP) system. 2(4) D-optimal mixture design with three level process variables was employed to develop SCFG particles, utilizing flow descriptors and hydrophobicity descriptors as response variables. The results indicated that blending of CFG (51.4% w/w) and magnesium silicate (MS) (48.6% w/w) using freeze-drying technique was found to have highest desirability (0.904). The developed SEP showed highest oil desorbing capacity, low self-emulsification time and highest drug content. It was observed that SCFG-SEP (F2 formulation) showed lowest PDI (0.2445 ± 0.03) as well as smallest particle size (127 ± 5.8 nm). The droplets were uniform and maintain their integrity after reconstitution (TEM analysis). Furthermore, APT-loaded SEP showed enhanced in vitro dissolution (4 folds) and ex vivo performance (7-fold enhanced Papp) as compared to pure APT. Furthermore, in vivo pharmacokinetic study showed that significant enhancement (p > 0.05) in Cmax was evident with APT-loaded F2 (SCFG-SEP) (1.93-fold) and F4 (Aerosil 200-SEP) (1.58-fold). The data also suggested increase in absorption rate when APT incorporated into SCFG-SEP. Thus, findings pointed toward enhanced bioavailability of APT when loaded into SCFG particles. Overall, the developed SCFG particles could be considered as a better alternative to already available solid carrier(s).
Asunto(s)
Emulsiones/química , Morfolinas/química , Silicatos/química , Zea mays/química , Animales , Aprepitant , Disponibilidad Biológica , Química Farmacéutica/métodos , Portadores de Fármacos/química , Emulsiones/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas , Masculino , Morfolinas/metabolismo , Tamaño de la Partícula , Polvos/química , Polvos/metabolismo , Ratas , Ratas Wistar , Dióxido de Silicio/química , Dióxido de Silicio/metabolismo , SolubilidadRESUMEN
Guggulu is an oleo-gum resin which exudes out as a result of injury from the bark of Commiphora wightii (Arnott) Bhandari [syn. Commiphora mukul (Hook. Ex Stocks) Engl; Balsamodendron mukul (Hook. Ex Stocks); Family, Burseraceae]. It has been used in the Ayurveda since time immemorial for the treatment of variety of disorders such as inflammation, gout, rheumatism, obesity, and disorders of lipids metabolism. It is a mixture of phytoconstituents like volatile oil which contains terpenoidal constituents such as monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids; steroids; flavonoids; guggultetrols; lignans; sugars; and amino acids. This review is an effort to compile all the information available on all of its chemical constituents which are responsible for its therapeutic potential. The wild occurrence of this species is restricted mainly to the dry regions of Rajasthan and Gujarat States of India, and the bordering regions of Pakistan. Oleo-gum resin, guggulu, tapped from the stems of this species, is consumed in high volumes by the Indian herbal industries. There has been a decline in its wild population over the last several decades, as a result of habitat loss and degradation, coupled with unregulated harvesting and tapping of oleo-gum resin. This species is consequently assessed as Critically Endangered and enlisted in the IUCN red list of threatened species.
RESUMEN
The aim of present investigation was to utilize quality by design (QbD) approach for extraction of tamarind pectin (TP) from Tamarindus indica L. pulp employing purity descriptors as indicator. The software generated quadratic equations showed significant effect of polarity index as compared to pulp concentration and boiling temperature on percentage yield and purity characteristics of TP. An insignificant effect on purity descriptors and percentage yield of TP upon replacement of acetone with methanol during predicted vs observed correlation studies (being similar polarity index of 5.1) pointed towards overwhelming influence of solvent polarity. Further, the FTIR-ATR, (1)H NMR, DSC and mass spectroscopy suggested TP was rhamnogalacturonan pectin with no tartaric acid content. TP was found to have significantly higher antioxidant activity as compare to apple pomace pectin, citrus peel pectin and commercial pectin. Overall, the physicochemical properties and antioxidant potential of TP could be utilized as an excipient for food and pharmaceutical industry.
Asunto(s)
Fraccionamiento Químico/métodos , Pectinas/química , Pectinas/aislamiento & purificación , Tamarindus/química , Secuencia de Carbohidratos , Datos de Secuencia Molecular , ReologíaRESUMEN
Aprepitant (APT) is a lipophilic, poorly water soluble drug with moderate permeability characteristic. Therefore, we aimed to improve solubility as well as permeability that could possibly improve oral bioavailability of APT. For this purpose, Quality by design (QbD) approach employing simplex lattice mixture design was used to prepare solid preconcentrated microemulsion (S-PCM). Further, the software generated numerically optimized S-PCM formulations were developed by utilizing desirability function. The spectral attributes (powder X-ray diffraction, ATR-FTIR, and differential scanning calorimetry) of S-PCM formulations suggested that APT was present in amorphous form. The results of droplet size (150-180 nm), zeta potential (-13 to -15 mV), poly dispersity index (PDI) (0.211-0.238) and emulsification time (<1 min), of these S-PCM formulations (SP1, SP2 and SP3) suggested spherical shape morphology (Transmission electron microscopy) with thermodynamic stability. The comparison of in vitro/ex vivo behavior of S-PCM (SP1) with micronized and non-micronized formulations of APT suggested 2-fold and 5-fold enhancement in solubility and permeability, respectively. This was further evident from pharmacokinetic studies in rabbits that showed 1.5-fold enhancement in bioavailability of S-PCM with respect to micronized APT. Thus, it could be envisaged that development of S-PCM formulation of APT is the best alternative to micronization technology based APT formulations reported earlier.
Asunto(s)
Antieméticos , Morfolinas , Administración Oral , Animales , Antieméticos/administración & dosificación , Antieméticos/química , Antieméticos/farmacocinética , Aprepitant , Disponibilidad Biológica , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Emulsiones , Yeyuno/metabolismo , Masculino , Morfolinas/administración & dosificación , Morfolinas/química , Morfolinas/farmacocinética , Permeabilidad , Conejos , Ratas , Solubilidad , SuspensionesRESUMEN
Mannich bases are the end products of Mannich reaction and are known as beta-amino ketone carrying compounds. Mannich reaction is a carbon-carbon bond forming nucleophilic addition reaction and is a key step in synthesis of a wide variety of natural products, pharmaceuticals, and so forth. Mannich reaction is important for the construction of nitrogen containing compounds. There is a number of aminoalkyl chain bearing Mannich bases like fluoxetine, atropine, ethacrynic acid, trihexyphenidyl, and so forth with high curative value. The literature studies enlighten the fact that Mannich bases are very reactive and recognized to possess potent diverse activities like anti-inflammatory, anticancer, antifilarial, antibacterial, antifungal, anticonvulsant, anthelmintic, antitubercular, analgesic, anti-HIV, antimalarial, antipsychotic, antiviral activities and so forth. The biological activity of Mannich bases is mainly attributed to α, ß-unsaturated ketone which can be generated by deamination of hydrogen atom of the amine group.
RESUMEN
Hydrazones are a special class of organic compounds in the Schiff base family. Hydrazones constitute a versatile compound of organic class having basic structure (R1R2C=NNR3R4). The active centers of hydrazone, that is, carbon and nitrogen, are mainly responsible for the physical and chemical properties of the hydrazones and, due to the reactivity toward electrophiles and nucleophiles, hydrazones are used for the synthesis of organic compound such as heterocyclic compounds with a variety of biological activities. Hydrazones and their derivatives are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal, anti-HIV, and so forth. The present review summarizes the efficiency of hydrazones as potent anti-inflammatory agents.
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We report the synthesis and biological assessment of 1,3,4-oxadiazole substituted 24 derivatives as novel, potential antibacterial agents. The structures of the newly synthesized derivatives were established by the combined practice of UV, IR, (1)H NMR, (13)C NMR, and mass spectrometry. Further these synthesized derivatives were subjected to antibacterial activity against all the selected microbial strains in comparison with amoxicillin and cefixime. The antibacterial activity of synthesized derivatives was correlated with their physicochemical and structural properties by QSAR analysis using computer assisted multiple regression analysis and four sound predictive models were generated with good R(2), R(adj)(2), and Fischer statistic. The derivatives with potent antibacterial activity were subjected to molecular docking studies to investigate the interactions between the active derivatives and amino acid residues existing in the active site of peptide deformylase to assess their antibacterial potential as peptide deformylase inhibitor.
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Antiinfecciosos/química , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Oxadiazoles/química , Oxadiazoles/farmacología , Amidohidrolasas/química , Aminoácidos/química , Amoxicilina/farmacología , Dominio Catalítico , Cefixima/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Nonionic surfactant vesicles (niosomes) were formulated with an aim of enhancing the oral bioavailability of tenofovir disoproxil fumarate (TDF), an anti-HIV drug. Niosomes were formulated by conventional thin film hydration technique with different molar ratios of surfactant, cholesterol, and dicetyl phosphate. The formulated niosomes were found spherical in shape, ranging from 2.95 µm to 10.91 µm in size. Vesicles with 1 : 1 : 0.1 ratios of surfactant : cholesterol : dicetyl phosphate with each grade of span were found to have higher entrapment efficiencies, which were further selected for in vitro and in vivo studies. Vesicles formulated with sorbitan monostearate were found to have maximum drug release (99.091%) at the end of 24 hours and followed zero order release kinetics. The results of in vivo study revealed that the niosomes significantly enhanced the oral bioavailability of TDF in rats after a dose of 95 mg/kg. The average relative bioavailability of niosomes in relation to plane drug solution was found to be 2.58, indicating more than twofold increase in oral bioavailability of TDF. Significant increase in mean residential time (MRT) was also found, reflecting release retarding efficacy of the vesicles. In conclusion, niosomes could be a promising delivery for TDF with improved oral bioavailability and prolonged release profiles.
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Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/farmacocinética , Química Farmacéutica , Liposomas/química , Adenina/administración & dosificación , Adenina/análogos & derivados , Adenina/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Cinética , Masculino , Organofosfonatos/administración & dosificación , Organofosfonatos/farmacocinética , Tamaño de la Partícula , Ratas , TenofovirRESUMEN
A series of benzamide substituted Mannich bases (1-7) were synthesized. The synthesized derivatives were authenticated by TLC, UV-Visible, FTIR, NMR, and mass spectroscopic techniques and further screened for in vitro antibacterial activity by test tube dilution method using amoxicillin and cefixime as standard drugs. The compounds 5, 6, and 7 were found to be the most active antibacterial agents among all the synthesized compounds. The physicochemical similarity of the compounds with standard drugs was assessed by calculating various physicochemical properties using software programs. The percent similarity of synthesized compounds was found to be good and compound 1 was found to have higher percentage of similarity. The compounds were subjected to QSAR by multilinear regression using Analyze it version 3.0 software, and four statistically sound models were developed with R2 (0.963-0.997), Radj2 (0.529-0.982), and Q2 (0.998-0.999) with good F (2.35-65.56) values.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Benzamidas/síntesis química , Benzamidas/farmacología , Diseño de Fármacos , Relación Estructura-Actividad Cuantitativa , Cromatografía en Capa Delgada/métodos , Biología Computacional/métodos , Escherichia coli/efectos de los fármacos , Escherichia coli/fisiología , Bases de Mannich/síntesis química , Bases de Mannich/farmacología , Pruebas de Sensibilidad Microbiana/métodos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiologíaRESUMEN
The concentration of radium, thorium and potassium and radon exhalation rates in soil samples collected from Shivalik foot hills in the states of Haryana and Himachal Pradesh (India) were experimentally measured. A high-resolution gamma-ray spectroscopic system was used for the measurement of natural radioactivity ((226)Ra, (232)Th and (40)K) at Inter-University Accelerator Center, New Delhi, using a coaxial n-type high-purity germanium detector (EG&G, ORTEC, Oak Ridge, USA). The mass exhalation rates (EM) of radon in soil samples from the study area measured by 'sealed canister technique' using LR-115 type II track detectors varied from 50±1 to 143±6 mBqkg(-1) h(-1). The activity concentrations of (226)Ra, (232)Th and (40)K in various soil samples of the study area varied from 31±1.3 to 63±4.6, 53±1.8 to 78±2.6 and 472±4.8 to 630±7.0 Bq kg(-1) respectively. The results indicated some higher levels of radioactivity in Lal Dhang peak area of the hills compared with other locations under study.