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1.
Arch Pharm (Weinheim) ; 351(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29283449

RESUMO

Oxaprozin is a popular non-steroidal anti-inflammatory drug (NSAID) and its chronic oral use is clinically restricted due to its gastrointestinal (GI) complications. In order to circumvent the GI complications, oxaprozin was amended as a prodrug in a one-pot reaction using N,N-carbonyldiimidazole as an activating agent. Dextran of average molecular weight (60,000-90,000 Da) was exploited as a carrier in the process of oxaprozin prodrug production by esterification. The structural profiles of the synthesized oxaprozin prodrug were characterized by FT-IR and NMR spectroscopy. The oxaprozin prodrug possessed optimal molecular weight, lipophilicity, partition coefficient, protein binding, and degree of substitution of 52.4%. The release of oxaprozin upon hydrolysis of the prodrug in both simulated gastric fluid and simulated intestinal fluid followed first-order kinetics with 55.2 min of half-life. Varied ADME properties of the prodrug resulted upon Schrodinger's QikProp tool application. Oxaprozin prodrug displayed significant analgesic, antipyretic, and anti-inflammatory activities, with a remarkable decrease in the ulcer index and being devoid of antigenicity in experimental animals. Thus, it is evident that oxaprozin prodrug is a safer oral NSAID without causing any ulcerations.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antipiréticos/uso terapêutico , Edema/tratamento farmacológico , Pró-Fármacos/uso terapêutico , Propionatos/uso terapêutico , Analgésicos/administração & dosagem , Analgésicos/química , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Antipiréticos/administração & dosagem , Antipiréticos/química , Carragenina , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Feminino , Hidrólise , Masculino , Estrutura Molecular , Peso Molecular , Oxaprozina , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Propionatos/administração & dosagem , Propionatos/química , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Úlcera/tratamento farmacológico
2.
Recent Pat Drug Deliv Formul ; 11(3): 221-229, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29237390

RESUMO

BACKGROUND: Poor oral absorption of budesonide limits the design of its solid oral dosage form. With this context, multiparticulate pulsatile system of budesonide for chronotherapy of nocturnal asthma was aimed in this study. METHODS: Initially, solid dispersions of budesonide (BD) using sodium starch glycolate (SSG) and guar gum (GG) were developed and characterized. Uniform sized non-pareil seeds (~400 µm) were coated with solid dispersions to obtain immediate (BMP) and controlled release pellets by solution layering technique. Rationale of selection of BD in this research was based on recent patents such as diltiazem HCl (US5914134) and multipar-ticulate systems (US5017381). Pulsatile drug release pellets (BMPP) of BD were obtained by coating the controlled release pellets with Eudragit L100 and RS 100. Pellets were assessed by saturation sol-ubility, FTIR, DSC, micromeritic, SEM, drug content, drug release, pharmacokinetic and stability studies. RESULTS: Solubility of BD was increased by 22 folds due to inter-particle distribution of BD and polymers in solid dispersions. No changes in characteristic functional groups of BD had indicated the compatibility of drug with polymers as noticed in FTIR and DSC. Fluidized bed processor enabled the production of spherical and uniformly distributed pellets with optimum angle of repose (12-19°) and friability (<1%). Solution layering technique employed in preparation of pellets had facilitated with moderately high BD content (91.5-99.6%) and 100% drug release at the end of 12hr. The pulsatile release pellets (BMPP) produced 6hr lag phase followed by 12hr controlled release. Promised pharmacokinetics was resulted as Cmax of 380ng/ml for BMP-2 and 162ng/ml for BMPP-5 and Tmax of 5 hr for BMP-2 and 12hr for BMPP-5. Increased pharmacokinetics was the direct results of increased solubility of BD due to application of solid dispersion and solution layering on pellets. CONCLUSIONS: Chronopharmacokinetics of BD were achieved with the help of Eudragit coatings on pellets. The BMP and BMPP formulations were found to be reasonably stable over a period of time. Thus, optimal chronopharmacokinetics of BD was achieved successfully by multiparticulate pulsatile technology.


Assuntos
Antiasmáticos/administração & dosagem , Antiasmáticos/farmacocinética , Budesonida/administração & dosagem , Budesonida/farmacocinética , Cronofarmacocinética , Animais , Antiasmáticos/química , Asma/tratamento farmacológico , Budesonida/química , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Excipientes , Masculino , Tamanho da Partícula , Material Particulado , Patentes como Assunto , Coelhos , Solubilidade
3.
Curr Drug Discov Technol ; 11(3): 169-80, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25466399

RESUMO

Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Administração Cutânea , Animais , Emulsões/administração & dosagem , Humanos , Hidrogéis/administração & dosagem , Hidrogéis/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia , Viscosidade
4.
Curr Drug Discov Technol ; 11(3): 189-96, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25176281

RESUMO

OBJECTIVE: The research aims to formulate and develop the controlled release profile of glibenclamide by encapsulating glibenclamide into niosomes followed by incorporation into an aqueous gel base. MATERIALS AND METHODS: Glibenclamide incorporated niosomes were prepared by a modified ether injection technique using Span 20/Span 80 and cholesterol. The prepared niosomes were evaluated for chemical incompatibility by FT-IR, morphology, vesicle dimension, encapsulation efficiency, in-vitro diffusion and drug release kinetics. Niosomal gels were prepared by incorporating the optimized niosomes into a gel base containing Carbopol 934 and evaluated for viscosity, in-vitro diffusion and in-vivo pharmacodynamic activity. RESULTS AND DISCUSSION: The results indicated that relationship between the amount of Span and niosomal vesicular diameter was inversely proportional. Microscopic images have illustrated the sphere shape vesicles. The cumulative percentage of drug release from niosomal suspension was observed in the order GN-4>GN-2>GN- 6>GN-5>GN-3>GN-1. Glibenclamide gel showed highest percentage drug release when compared to niosomal gel. Invivo study revealed that the glibenclamide incorporated niosomal gel formulation; GNG-1 is more efficient in lowering blood glucose levels in experimental animals. CONCLUSION: The niosomal gel of glibenclamide had released the drug in well controlled manner which is supported by pharmacodynamic activity with evidence of consistent lowering of blood glucose levels.


Assuntos
Química Farmacêutica/métodos , Géis/química , Glibureto/química , Lipossomos/química , Animais , Glicemia/efeitos dos fármacos , Géis/farmacologia , Glibureto/farmacologia , Lipossomos/farmacologia , Masculino , Ratos , Ratos Wistar
5.
Curr Drug Discov Technol ; 11(3): 181-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24836404

RESUMO

Cubosomes are reversed bicontinuous cubic phases and possess unique physicochemical properties. These special systems are receiving much attention for the delivery of various hydrophilic, hydrophobic and amphiphilic drugs with enhanced bioavailability and high loading capacity. A wide variety of drugs are applicable for cubosome formulation for various routes of delivery. The lipids used in cubosome formulation are more stable and offer stability to the formulation during shelf-life. The article reviews about the back ground, techniques of cubosome preparation such as high pressure homogenization, probe ultrasonication and automated cubosome preparation; and also methods of cubosomes preparation such as top down, bottom up and other methods with pictorial presentation. This article emphasizes the phase transition and also targeted approaches of cubosomes. The characterization studies for cubosomes such as cryo transmission electron microscopy, differential scanning calorimetry and scanning electron microscopy followed by in-vitro and in-vivo evaluation studies of cubosomes were explained with appropriate examples. Recent applications of cubosomes were explained with reference to flurbiprofen, odorranalectin, diazepam and dexamethasone. The advantages, disadvantages and limitations of cubosomal technology were emphasized.


Assuntos
Biofarmácia/métodos , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Química Farmacêutica , Nanopartículas/administração & dosagem , Tamanho da Partícula
6.
Curr Drug Discov Technol ; 11(2): 127-32, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24467591

RESUMO

For ages aspirin has established its value as an analgesic, anti-inflammatory drug, but in 1938, it was found to be a causative factor of gastric inflammation (ulcer). Later discovered non-steroidal anti-inflammatory drugs (NSAIDs) were found effective as aspirin but failed to overcome the goal of safer aspirin. As the method of prostaglandin inhibition through COX is a common mechanism to both the wanted and unwanted effects of aspirin and non-aspirin NSAIDs, the COX enzyme becomes a target for drug designers for the development of the "safe aspirin". In the late 1990s, a new class of drug molecules collectively known as selective inhibitors of cyclooxygenase-2(Coxibs) was developed for the treatment of pain and inflammation. Coxibs developed were as efficacious as the common NSAIDs, but they are devoid of major side effect, the gastrointestinal bleeding. This review presents an overview on all the discovered COX-2 inhibitors, their physiological role, side effects and reasons of their withdrawal.


Assuntos
Anti-Inflamatórios não Esteroides , Inibidores de Ciclo-Oxigenase 2 , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Humanos , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/metabolismo
7.
Curr Drug Discov Technol ; 11(2): 162-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24295369

RESUMO

The aim of the investigation was to prepare nimesulide emulsion for incorporation in Aloe vera gel base to formulate 'nimesulide - Aloe vera transemulgel' (NAE) and to carryout in-vitro assessment and in-vivo anti-inflammatory studies of the product. Although the use of nimesulide is banned for oral administration, due to its potential for inducing hepatotoxicity and thrombocytopenia, the use of nimesulide for topical delivery is prominent in the treatment of many inflammatory conditions including rheumatoid arthritis. The drug loading capacity of transdermal gels is low for hydrophobic drugs such as nimesulide. Nimesulide can be effectively incorporated into emulgels (a combination of emulsion and gel). Aloe vera has a mild anti-inflammatory effect and in the present study Aloe vera gel was formulated and used as a gel base to prepare NAE. The emulgels thus prepared were evaluated for viscosity, pH, in-vitro permeation, stability and skin irritation test. In-vivo anti-inflammatory studies were performed using carrageenan induced hind paw edema method in Wistar rats. The results were compared with that of commercial nimesulide gel (CNG). From the in-vitro studies, effective permeation of nimesulide from NAE (53.04 %) was observed compared to CNG (44.72 %) at 30 min indicating better drug release from NAE. Topical application of the emulgel found no skin irritation. Stability studies proved the integrity of the formulation. The percentage of inhibition of edema was highest for the prepared NAE (67.4 % inhibition after 240 min) compared to CNG (59.6 %). From our results, it was concluded that the Aloe vera gel acts as an effective gel base to prepare nimesulide emulgel with high drug loading capacity (86.4 % drug content) compared to CNG (70.5 % drug content) with significant anti-inflammatory effect.


Assuntos
Anti-Inflamatórios não Esteroides , Preparações de Plantas , Sulfonamidas , Aloe , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Carragenina , Estabilidade de Medicamentos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Géis , Concentração de Íons de Hidrogênio , Masculino , Preparações de Plantas/química , Preparações de Plantas/farmacologia , Preparações de Plantas/uso terapêutico , Ratos Wistar , Pele/efeitos dos fármacos , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Viscosidade
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