RESUMEN

A cephalexin (CEP) self-nanoemulsifying drug delivery system (SNEDDS) was developed in this study to improve the drug's oral administration. The CEP-SNEDDS was made utilizing an aqueous titration method employing Lauroglycol 90, Poloxamer 188, and Transcutol-HP. Box-Behnken design (BBD) with three factors at three levels was used for optimization, and their impacts on globule size (nm), transmittance (percent), and emulsification time (s) were assessed. The optimized formulation (Opt-F3) was further tested for zeta potential, refractive index, percent transmittance, thermodynamic stability, in-vitro release, ex vivo permeability, antibacterial activity, and bioavailability. The chosen formulation (Opt-F3) had a globule size of 87.25 ± 3.16 nm, PDI of 0.25, zeta potential of -24.37 mV, self-emulsification duration of 52 ± 1.7 s, and percentage transmittance of 99.13 ± 1.5%, viscosity of 96.26 ± 2.72 cp, and refractive index of 1.29 ± 0.1. It showed a sustained release profile (94.28 ± 5.92 percent in 24 h). The Opt-F3 formulation had 3.95 times the permeability of CEP-dispersion. In comparison to CEP-dispersion, it also demonstrated greater antibacterial efficacy against tested Gram-positive and Gram-negative pathogens. The oral bioavailability of Opt-F3 is 3.48 times higher than that of CEP-dispersion, according to an in-vivo investigation. It has been determined that the prepared CEP-SNEDDS may be an advantageous carrier for CEP delivery.

RESUMEN

ABSTRACT A simple and sensitive HPLC method was developed and validated for the quantification of haloperidol in solid lipid nanoparticles (SLNs). The developed method was used for detection of shelf life of haloperidol in SLNs. Calibration curve of haloperidol was also constructed in rat plasma using loratidine as internal standard. In vivo studies were performed on rats and concentration of haloperidol in brain and blood was measured for the determination of various pharmacokinetic and hence brain targeting parameters. Chromatogram separation was achieved using C18 column as stationary phase. The mobile phase consisted of 100 mM/L potassium dihydrogen phosphate-acetonitrile-TEA (10:90:0.1, v/v/v) and the pH was adjusted with o-phosphoric acid to 3.5. Flow rate of mobile phase was 2 mL/minute and eluents were monitored at 230 nm using UV/VIS detector. The method was validated for linearity, precision, accuracy, reproducibility, limit of detection (LOD) and limit of quantification (LOQ). Linearity for haloperidol was in the range of 1-16 µg/mL. The value of LOD and LOQ was found to be 0.045 and 0.135 μg/mL respectively. The shelf life of SLNs formulation was found to be 2.31 years at 4 oC. Various parameters like drug targeting index (DTI), drug targeting efficiency (DTE) and nose-to-brain direct transport (DTP) were determined for HP-SLNs & HP-Sol administered intranasally to evaluate the extent of nose-to-brain delivery. The value of DTI, DTE and DTP for HP-SLNs was found to be 23.62, 2362.43 % and 95.77% while for HP-Sol, values were 11.28, 1128.61 % and 91.14 % respectively.

Asunto(s)

Animales , Masculino , Femenino , Ratas , Cromatografía Líquida de Alta Presión/clasificación , Crecimiento y Desarrollo , Nanopartículas/estadística & datos numéricos , Haloperidol/análisis , Haloperidol/farmacocinética , Plasma/metabolismo , Técnicas In Vitro/instrumentación

RESUMEN

In the present study, haloperidol (HP)-loaded solid lipid nanoparticles (SLNs) were prepared to enhance the uptake of HP to brain via intranasal (i.n.) delivery. SLNs were prepared by a modified emulsification-diffusion technique and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release, and stability. All parameters were found to be in an acceptable range. In vitro drug release was found to be 94.16±4.78% after 24 h and was fitted to the Higuchi model with a very high correlation coefficient (R (2)=0.9941). Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography. The brain/blood ratio at 0.5 h for HP-SLNs i.n., HP sol. i.n. and HP sol. i.v. was 1.61, 0.17 and 0.031, respectively, indicating direct nose-to-brain transport, bypassing the blood-brain barrier. The maximum concentration (C max) in brain achieved from i.n. administration of HP-SLNs (329.17±20.89 ng/mL, T max 2 h) was significantly higher than that achieved after i.v. (76.95±7.62 ng/mL, T max 1 h), and i.n. (90.13±6.28 ng/mL, T max 2 h) administration of HP sol. The highest drug-targeting efficiency (2362.43%) and direct transport percentage (95.77%) was found with HP-SLNs as compared to the other formulations. Higher DTE (%) and DTP (%) suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations.

RESUMEN

A series of twelve compounds (Compounds RNH1-RNH12) of acid hydrazones of pyridine-3-carbohydrazide or nicotinic acid hydrazide was synthesized and evaluated for anticonvulsant activity by MES, scPTZ, minimal clonic seizure and corneal kindling seizure test. Neurotoxicity was also determined for these compounds by rotarod test. Results showed that halogen substitution at meta and para position of phenyl ring exhibited better protection than ortho substitution. Compounds RNH4 and RNH12, were found to be the active analogs displaying 6Hz ED50 of 75.4 and 14.77 mg/kg while the corresponding MES ED50 values were 113.4 and 29.3 mg/kg respectively. In addition, compound RNH12 also showed scPTZ ED50 of 54.2 mg/kg. In the series, compound RNH12 with trifluoromethoxy substituted phenyl ring was the most potent analog exhibiting protection in all four animal models of epilepsy. Molecular docking study has also shown significant binding interactions of these two compounds with 1OHV, 2A1H and 1PBQ receptors. Thus, N-[(meta or para halogen substituted) benzylidene] pyridine-3-carbohydrazides could be used as lead compounds in anticonvulsant drug design and discovery.

Asunto(s)

Anticonvulsivantes/química , Hidrazonas/química , Fármacos Neuroprotectores/química , Niacinamida/análogos & derivados , Convulsiones/tratamiento farmacológico , Animales , Anticonvulsivantes/síntesis química , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Simulación por Computador , Córnea/fisiología , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Electrochoque , Hipocampo/efectos de los fármacos , Hidrazonas/síntesis química , Hidrazonas/farmacología , Hidrazonas/uso terapéutico , Excitación Neurológica/efectos de los fármacos , Ratones , Estructura Molecular , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Neurotoxinas/toxicidad , Niacinamida/síntesis química , Niacinamida/química , Niacinamida/farmacología , Niacinamida/uso terapéutico , Pentilenotetrazol/toxicidad , Pilocarpina/toxicidad , Prueba de Desempeño de Rotación con Aceleración Constante , Convulsiones/inducido químicamente , Convulsiones/etiología , Relación Estructura-Actividad

RESUMEN

The objective of the present work was to develop a suitable transdermal drug delivery system for nitrendipine. Polymeric films of nitrendipine were prepared by the film casting technique (glass ring) on mercury substrate. They were evaluated for physicochemical parameters, in vitro release and ex vivo permeation (heat separated human epidermis). Release of the drug from the films followed anomalous transport (0.5 < n < 1).Polymeric combination containing Eudragit RL 100:PVP K 30 in a 4:6 ratio showed the best results. Maximum drug release and skin permeability coefficient in 48 h were 85.8% and 0.0142 cm h(-1), respectively, in formulation C3 (Eudragit RL 100/Plasdone S 630; 4:6) and 88.0% and 0.0155 cm h(-1), respectively, in formulation, D3 (Eudragit RL 100/PVP K 30; 4:6). FTIR and TLC studies indicated no drug and polymer interaction.

Asunto(s)

Sistemas de Liberación de Medicamentos , Epidermis/metabolismo , Nitrendipino/administración & dosificación , Ácidos Polimetacrílicos/síntesis química , Polivinilos/síntesis química , Povidona/síntesis química , Administración Cutánea , Química Farmacéutica , Estabilidad de Medicamentos , Humanos , Nitrendipino/farmacocinética , Permeabilidad , Vehículos Farmacéuticos , Polivinilos/química , Espectroscopía Infrarroja por Transformada de Fourier

RESUMEN

The purpose of this research was to evaluate the effect of penetration enhancers on permeation kinetics of nitrendipine (NTP) through two different skin models. The permeation profile and related kinetics parameters such as activity parameter, diffusion parameter, lag time, relative activity parameter and relative diffusion parameter of NTP was determined in presence of some novel and widely accepted permeation enhancers. Among all the more pronounced enhancing effect was obtained with oleic acid (OA) as it presented the highest permeability coefficient. The enhancement was found to be increased in the following order: Dimethyl sulphoxide (DMSO)

Asunto(s)

Bloqueadores de los Canales de Calcio/farmacocinética , Excipientes/farmacología , Nitrendipino/farmacocinética , Absorción Cutánea/efectos de los fármacos , Administración Cutánea , Animales , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/química , Interpretación Estadística de Datos , Dimetilsulfóxido/farmacología , Excipientes/química , Ácidos Grasos no Esterificados/farmacología , Humanos , Técnicas In Vitro , Miristatos/farmacología , Nitrendipino/administración & dosificación , Nitrendipino/química , Ácido Oléico/farmacología , Aceites de Plantas/farmacología , Ratas , Solubilidad , Estimulación Química

RESUMEN

OBJECTIVE: In an attempt to find a better treatment for bacterial infections and burn wounds, various semisolid formulations containing 5% w/w of norfloxacin were prepared and evaluated for physicochemical parameters, in vitro drug release through cellophane membrane, antimicrobial activity, and burn wound healing properties. The prepared formulations were compared with silver sulfadiazine 1% cream, USP. METHODS: Various semisolid formulations were prepared with different bases like Carbopol, polyethylene glycol, and hydroxypropylmethyl cellulose, using standard procedures. The antimicrobial activity of these semisolid norfloxacin formulations, against various strains of aerobic and anaerobic microorganisms, was evaluated by using a standard cup-plate method. The wound healing property was evaluated by measuring the wound contraction and expressed as percentage of contraction of original wound size for each animal group. RESULTS: Antimicrobial activity of norfloxacin semisolid formulations was found to be equally effective against both aerobic and anaerobic bacteria in comparison to a formulation of silver sulfadiazine 1% cream, USP, available on the market. CONCLUSION: The burn wound healing property of the prepared norfloxacin semisolid formulations was found to be in good agreement with silver sulfadiazine 1% cream, USP, available on the market.