Rheological characterization of Poloxamer 407 nimesulide gels

The thermal gelling property of Poloxamer 407-nimesulide gels was characterized by rheological studies. Nimesulide, a local anti-inflammatory and anesthetic drug used for the treatment of acute and chronic pain,has a short duration of action and a long-acting single-dose injection would be of clinical importance. Thus a poloxamer 407 gel applied intramuscularly could prolong the release and action of nimesulide. In this study, aqueous gels with nimesulide, containing three different concentrations of Poloxamer 407, were prepared. Viscosity measurements were performed by rheologial studies to obtain the optimal sol-gel transition temperature. Poloxamer 407 gels are pseudoplastic and viscoelastic materials, which have an elastic modulus (G), characteristic of the solid, and a viscous modulus (G), characteristic of the liquid material. Moreover, being pseudoplastic gels, when they are deformed by shearing,their viscosity decreases. Increase of the polymer concentration increased the viscosity of the gels, which could affect the releasing process of nimesulide. Furthermore, the presence of nimesulide led to a lowering of the sol-gel transition temperature

Nimesulide PLA microspheres as a potential sustained release system for the treatment of inflammatory diseases.

Polylactic acid (PLA-L) microspheres were prepared as a biodegradable polymeric carrier for a non-steroidal anti-inflammatory drug, nimesulide. The preparation of this system was performed by the classical emulsion solvent-evaporation method. Size analysis of the microparticulate system showed that unloaded and loaded nimesulide-PLA microspheres had average diameters of about 42.9 nm and 2.1 microm, respectively. Scanning electron microscopy (SEM) of loaded and unloaded microsphere samples showed that the particles shape were perfectly spherical, the loading efficiency of nimesulide in PLA microspheres was 70%; Thus, the microparticle system evaluated in this work showed the potential to act as a sustained release system for nimesulide: in vitro dissolution profiles showed the PLA-L microparticles were able to sustain the release of the drug for a considerable period of time (28.7% within 108 h).

Sustained release of lidocaine from Poloxamer 407 gels.

In this work, we show that alteration of P407 gel content can affect drug release rates. The inorganic salts and PEG 400 commonly included in the formulation of P407 gels can also change the rate at which a drug is released. Lidocaine was selected as a model drug because, although widely used in the treatment of pain, its use is limited by short duration of its effects. The use of P407 gels prolongs the residence time of the lidocaine at the injection site, sustains drug release and increases therapeutic efficacy. Release studies were performed in a diffusion system. During release, data followed the Higuchi square root law time kinetic (r>0.98). Increased polymer concentration in the gel increases viscosity and reduces lidocaine release rates and diffusion coefficients via extended gel dissolution time and prolonged drug diffusion through the gel matrix. Lidocaine release rates and diffusion coefficients increased in gels composed of NaCl or PEG 400 aqueous solution. Because these additives are hydrophilic, they reduce gel dissolution time, thereby accelerating drug diffusion. Poloxamer is biocompatible and the results support the possibility of using Poloxamer gel as a sustained release injectable formulation.

Avaliação de prescrições de medicamentos para pacientes com Diabetes Mellitus atendidos por uma Unidade Básica de Saúde / Evaluation of the prescriptions of medicines to subjects with Diabetes Mellitus assisted by a basic Unit of Health

O Diabetes Mellitus (DM) é uma síndrome decorrente da falta de insulina e/ou da incapacidade da insulina de exercer adequadamente seus efeitos, devido à redução da sensibilidade dos tecidos a este hormônio.O Diabetes Mellitus tipo 2 (DM2), atinge entre 80 a 90 por cento da população diabética, sendo que cerca de 7,6 por cento dos indivíduos com idade entre 30 e 69 anos são portadores de DM, aumentando para 20 por cento nos pacientes com idade superior a 70 anos.Além da obesidade, o aumento da mortalidade nos pacientes com DM2 está relacionado à agregação de vários fatores de risco, como hipertensão arterial sistêmica, dislipidemia e ausência de informações do paciente em relação à sua patologia.O tratamento do DM baseia-se no aumento da atividade física, suspensão do fumo, hábitos alimentares corretos e, se necessário, uso de insulina e antidiabéticos orais.Esse trabalho realizou um levantamento farmacoepidemiológico com 130 pacientes portadores de DM atendidos pela UBS São José em Ribeirão Preto, SP.Foram avaliadas as 130 prescrições medicamentosas indicadas aos usuários, com relação aos fármacos prescritos, bem como as doses e o tipo de DM de cada paciente.Os pacientes diagnosticados com DM2 utilizaram para o tratamento quatro esquemas terapêuticos distintos:monoterapia com glibenclamida(38,5 por cento),monoterapia com metformina (24,6por cento), metformina associada com glibenclamida (19,2 por cento) e metformina associada com insulina (5,4 por cento).Dos usuários, 12,3 por cento eram portadores de DM1 e utilizaram apenasinsulina.Concluiu-se que a prescrição racional e o seguimento farmacoterapêutico podem diminuir a incidência de comorbidades e melhorar a adesão dos pacientes portadores de DM.

Photophysicals and photochemicals studies of zinc(II) phthalocyanine in long time circulation micelles for photodynamic therapy use.

Long time circulation systems, such as polymeric micelles, represent a growing area in biomedical research. These microparticles can be used in many biological systems to provide appropriate drug levels with a specific biodistribution. Long time circulation micelles (LTCM) were routinely prepared using PEG-5000-DSPE (polyethyleneglycol-5000-distearoil-phosphatidyl-ethanolamine) and zinc(II) phthalocyanine (ZnPc) as a photosensitizer and fluorescent probe. This compound belongs to a second generation of photoactive agents, mainly used in photodynamic therapy (PDT) of neoplasic tissues. Their high selectivity for tumoral target tissues as well as high phototoxicity based on singlet oxygen generation renders the utilization of these compounds feasible as an alternative therapy for cancer treatment. LTCM were characterized by classical spectroscopic techniques. Absorbance measurements indicated that the drug was s completely loaded into LTCM (epsilon = 2.41 x 10(5) cm(-1)). This was also verified by steady state and time-resolved fluorescence measurements. The lifetime profiles of ZnPc decay curves were fitted according to biexponential function (tau1 = 3.9 ns and tau2 = 15.5 ns) indicating different locations for ZnPc into LTCM. The time-resolved spectroscopy measurements for ZnPc triplet excited state lifetimes (tauT) were calculated from the kinetic analysis of transient decays at the absorption maximum (480 nm), by using laser flash photolysis technique. All the spectroscopy measurements performed allowed us to conclude that, ZnPc in LTCM is a promising drug delivery system (DDS) for PDT.

Rheological characterization of Poloxamer 407 lidocaine hydrochloride gels.

Thermal gelation of Poloxamer 407 lidocaine hydrochloride gels was characterized by rheological studies. Lidocaine, a local anesthetic used for treatment of acute and chronic pain, presents short duration action; thus a long-action single-dose injection would be of clinical importance. Poloxamer 407 gel can extend the release and the action of lidocaine. In the present work, aqueous gels with lidocaine containing different concentrations of Poloxamer 407 and additives like inorganic salts (NaCl, NaH(2)PO(4), Na(2)CO(3)) and PEG 400 were obtained. Viscosity measurements and the optimal sol-gel transition temperature were obtained by these rheological studies. Poloxamer 407 gels are viscoelastic materials because they have elastic modulus (G'), characteristic of solid materials, and viscous modulus (G"), characteristic of liquid materials. Poloxamer 407 gels are pseudoplastic; therefore, when shear deformed, their viscosity decreases. Increase of the polymer concentration increases the viscosity of the gels, which can change the releasing process of lidocaine from the gel. The sol-gel transition temperature was decreased by increasing the polymer concentration and by the presence of additives. The rheological behaviour of Poloxamer gels characterized in this work can be useful for understanding further studies of drug release.

Stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: preparation and in vitro permeation study.

BACKGROUND: Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs) in order to optimize its skin delivery in Photodynamic Therapy (PDT) of skin cancers. METHODS: SCLLs were obtained by reverse phase evaporation technique and size distribution of the vesicles was determinated by photon correlation spectroscopy. In vitro permeation profile was characterized using hairless mouse skin mounted in modified Franz diffusion cell. RESULTS: Size exclusion chromatography on gel filtration confirmed vesicle formation. SCLLs obtained by presented a degree of encapsulation of 5-ALA around 5.7%. A distribution of vesicle size centering at around 500 nm and 400 nm respectively for SCLLs and SCLLs containing 5-ALA was found. In vitro 5-ALA permeation study showed that SCLLs preparations presented higher skin retention significantly (p < 0.05) on the epidermis without SC + dermis, with a decreasing of skin permeation compared to aqueous solution. CONCLUSIONS: The in vitro delivery performance provided by SCLLs lead to consider this systems adequate for the 5-ALA-PDT of skin cancer, since SCLLs have delivered 5-ALA to the target skin layers (viable epidermis + dermis) to be treated by topical PDT of skin cancer.

Potential use of gelcasting hydroxyapatite porous ceramic as an implantable drug delivery system.

Hydroxyapatite (HA) ceramic in a porous configuration is suggested as a drug release system. A new technique for the production of this material, based on the foaming of suspensions and in situ polymerization (gelcasting method), resulted in a material whose characteristics are likely to make it useful as an implantable drug delivery system. Three batches of HA ceramic with different porosities were characterized by X-ray diffraction and scanning electron microscopy (SEM). Pore size and shape as well as density were determined. In vitro experiments were performed in order to evaluate the dissolution behavior of cisplatin in the system. X-ray diffraction analysis showed that the final product consisted of a single phase, indicating that the sintering process had not affected the structure of the HA. Energy dispersive X-ray analysis (EDX) showed absence of impurities. Pore diameters were in the range 15--34 microm. SEM showed that the material presented a highly interconnected spheroidal porous network with open micropores and closed macropores. In vitro experiments showed significant differences in the release rate of cisplatin between three different porosities.

A vehicle for photodynamic therapy of skin cancer: influence of dimethylsulphoxide on 5-aminolevulinic acid in vitro cutaneous permeation and in vivo protoporphyrin IX accumulation determined by confocal microscopy.

Topical application of 5-aminolevulinic acid (5-ALA) followed by light irradiation is a new concept of photodynamic therapy (PDT) of skin cancers. 5-ALA is a prodrug that can be converted by the heme biosynthetic pathway into protoporphyrin IX, an effective photosensitizer. In the present work we propose the enhancement of 5-ALA-induced protoporphyrin IX accumulation by dimethylsulphoxide (DMSO) and ethylenediamine-tetraacetic acid disodium salt (EDTA). The presence of 20% DMSO (w/w) in oil-in-water emulsions increased the in vitro permeation of 5-ALA through hairless mouse skin. In vivo studies demonstrated a significant increase in the amount of protoporphyrin IX extracted from healthy hairless mouse skin after 3 h treatment with an oil-in-water emulsion containing 10% 5-ALA (w/w), 3% EDTA (w/w) and 20% DMSO (w/w). By confocal scanning laser microscopy imaging, an observed increase in red fluorescence, at 476 nm excitation and emission detected longer than 590 nm, in skin that had received this treatment, was attributed to protoporphyrin IX accumulation. Although no effect of EDTA on short-term protoporphyrin IX accumulation in skin was detected, this chelator could protect 5-ALA from decomposition during prolonged topical administration. The results obtained indicate that association of 5-ALA, EDTA and 20% DMSO may enhance the delivery of 5-ALA to the skin in the topical PDT.

Influence of lecithin on some physical chemical properties of poloxamer gels: rheological, microscopic and in vitro permeation studies.

Thermoreversible gels may be used in delivery systems which require a sol-gel transition at body temperature. The influence of the addition of lecithin, a permeation enhancer, on the rheological and in vitro permeation properties of poloxamer 407 gels was investigated. Light microscopy and rheological parameters were used to characterize the microscopic structure of the formulations which showed non Newtonian behaviour, pseudoplastic flow with a yield value. Increased concentrations of lecithin increased the thixotropy, yield value, apparent viscosity, and the gelation temperature of the gels. Light microscopy showed the formation of micellar structures by the addition of lecithin, which may account for changes in rheological properties. In vitro permeation of a model drug, triamcinolone acetonide, was decreased when the lecithin concentration was increased. The presence of lecithin in the poloxamer gel improved the characteristics for topical drug delivery.

Comparative bioavailability of sulfamethoxazole in co-trimoxazole suspensions containing different thickness agents.

Many workers have attempted to determine the bioavailability of pharmaceutical formulations, which is important to assure the efficacy and safety of medications. In the present study, we investigated the bioavailability of five formulations of the combination of 0.8% trimethoprim (TMP) and 4% sulfamethoxazole (SMZ) (co-trimoxazole) as a suspension, containing different types of thickness agents. The blood levels of a single oral dose administered to rats were compared. Bioavailability was determined by comparing the time to peak concentration (Tmax), peak serum concentration (Cmax), total area under the concentration time curve (AUC) and the elimination rate constant (Kel). Analysis of the pharmacokinetic parameters of SMZ showed significant differences between the formulations, indicating that the absorption of SMZ was affected by thickness type. The calculated bioavailabilities of oral TMP and SMZ were 381, 558, 695, 480, 559 and 554 micrograms/mL, respectively, and the preparation containing hydroxyethyl cellulose 4.400 H as a thickness agent showed the best bioavailability (AUC 0-infinity = 695.24; micrograms/mL; Cmax = 35.2 micrograms/mL).