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1.
Chem Biol Interact ; 347: 109599, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34343525

RESUMO

BACKGROUND: Geraniol, a natural monoterpene, is a component of many plant essential oils. It contains many medicinal and pharmacological properties. Doxorubicin is an anticancer drug; however, its clinical usage is limited due to its cumulative and dose-dependent cardiotoxicity. This study investigates geraniol as a protective agent against doxorubicin-induced cardiotoxicity and explores possible underlying mechanisms of action. METHODS: Male Sprague-Dawley rats were allocated into five groups. Groups 1 and 2 were administered saline and geraniol 200 mg/kg/day/orally, respectively, for 15 days. Group 3 was administered intraperitoneal doxorubicin (5 mg/kg/IP on the 5th, 10th and 15th days to achieve a cumulative dose of 15 mg/kg) to induce cardiotoxicity. The fourth and fifth groups were treated with either geraniol 100 mg/kg or 200 mg/kg orally and doxorubicin to equal the doxorubicin dose administered to Group 3. RESULTS: Treatment with geraniol significantly ameliorated cardiac damage and restored serum cardiac injury marker levels in doxorubicin treated animals. Geraniol upregulated Nrf2 and HO-1 expression, elevated total antioxidant capacity, decreased the nuclear accumulation of kappa-light-chain enhancer of activated B cells (NF-κB), decreased the phosphorylation and degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), suppressed tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin-18 (IL-18) levels, and restored the levels of Bax and caspase-3 and 9 in heart tissue. CONCLUSION: Geraniol may function as a potential activator of nuclear factor erythroid 2-related factor 2 (Nrf2), which subsequently improves Nrf2-dependent antioxidative signaling, diminishes apoptosis and subdues the inflammatory response. The downstream result is protection of the heart from doxorubicin-induced cardiotoxicity.


Assuntos
Monoterpenos Acíclicos/uso terapêutico , Cardiotônicos/uso terapêutico , Cardiotoxicidade/tratamento farmacológico , Cymbopogon/química , Doxorrubicina/toxicidade , Transdução de Sinais/efeitos dos fármacos , Animais , Cardiotoxicidade/patologia , Eletrocardiografia/efeitos dos fármacos , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Heme Oxigenase (Desciclizante)/metabolismo , Masculino , Mitocôndrias/efeitos dos fármacos , Miocárdio/patologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley
2.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200144

RESUMO

Natural products have been extensively used for treating a wide variety of disorders. In recent times, Brucine (BRU) as one of the natural medications extracted from seeds of nux vomica, was investigated for its anticancer activity. As far as we know, this is the first study on BRU anticancer activity against skin cancer. Thus, the rational of this work was implemented to develop, optimize and characterize the anticancer activity of BRU loaded ethosomal gel. Basically, thin film hydration method was used to formulate BRU ethosomal preparations, by means of Central composite design (CCD), which were operated to construct (32) factorial design. Two independent variables were designated (phospholipid percentage and ethanol percentage) with three responses (vesicular size, encapsulation efficiency and flux). Based on the desirability function, one formula was selected and incorporated into HPMC gel base to develop BRU loaded ethosomal gel. The fabricated gel was assessed for all physical characterization. In-vitro release investigation, ex-vivo permeation and MTT calorimetric assay were performed. BRU loaded ethosomal gel exhibited acceptable values for the characterization parameters which stand proper for topical application. In-vitro release investigation was efficiently prolonged for 6 h. The flux from BRU loaded ethosome was enhanced screening optimum SSTF value. Finally, in-vitro cytotoxicity study proved that BRU loaded ethosomal gel significantly improved the anticancer activity of the drug against A375 human melanoma cell lines. Substantially, the investigation proposed a strong motivation for further study of the lately developed BRU loaded ethosomal gel as a prospective therapeutic strategy for melanoma treatment.


Assuntos
Etanol/química , Géis/química , Pele/efeitos dos fármacos , Estricnina/análogos & derivados , Administração Cutânea , Animais , Géis/administração & dosagem , Masculino , Fosfolipídeos/química , Ratos , Ratos Wistar , Absorção Cutânea/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Estricnina/administração & dosagem , Estricnina/química
3.
Polymers (Basel) ; 13(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806659

RESUMO

Curcumin is a poorly water-soluble drug that is used for the treatment of inflammations, tumors, wound healing antioxidant and other diseases. In the current manuscript, it is successfully formulated into proniosome gels. The proniosomes are readily hydrated into niosomal formulations using warm water. Proniosomes were prepared using nonionic surfactants (tween 80, span 60) either solely or in combinations with cholesterol. The produced niosomal formulations were homogenous in size with vesicular sizes >343 and <1800 nm. The encapsulation efficiency percentage "EE%" of curcumin in niosomal formulations was different according to niosomal composition. It increased up to 99.74% in formulations of tween 80/Chol of 200 µmole/mL lipid concentration. Span 60/chol niosomes showed decreased curcumin EE%. Niosomal formulations showed increased SSTF and PC with enhancement ratios of more than 20-fold compared with curcumin suspension form. Kinetically, niosomes fitted to the Korsemeyer-Peppas model with non-Fickian transport according to their calculated n-values where curcumin suspension form showed Korsemeyer-Peppas kinetics with Fickian transport. Niosomal formulations deposited higher curcumin amounts in the skin compared with the suspension form. The best niosomal formulation (F9) was used for niosomal gel and emulgel fabrication. Finally, the anti-inflammatory activity of curcumin in various formulations was evaluated using a rat hind paw edema method and the % of swelling was 17.5% following 24 h in group treated with curcumin niosomal emulgel. In conclusion, this study suggests that the developed niosomal emulgel could significantly enhance the anti-inflammatory effect of curcumin and be an efficient carrier for the transdermal delivery of the drug.

4.
Polymers (Basel) ; 13(4)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672981

RESUMO

BACKGROUND: Curcumin (Cur) possesses a variety of beneficial pharmacological properties including antioxidant, antimicrobial, anti-cancer and anti-inflammatory activities. Nevertheless, the low aqueous solubility and subsequent poor bioavailability greatly limits its effectiveness. Besides, the role of myrrh oil as an essential oil in treating inflammatory disorders has been recently demonstrated. The objective of the current investigation is to enhance Cur efficacy via developing Cur nanoemulgel, which helps to improve its solubility and permeability, for transdermal delivery. METHODS: The formulated preparations (Cur gel, emulgel and nanoemulgel) were evaluated for their physical appearance, spreadability, viscosity, particle size, in vitro release and ex vivo drug permeation studies. The in vivo anti-inflammatory activity was estimated using the carrageenan-induced rat hind paw edema method. RESULTS: The formulated Cur-loaded preparations exhibited good physical characteristics that were in the acceptable range of transdermal preparations. The release of Cur from gel, emulgel and nanoemulgel after 12 h was 72.17 ± 3.76, 51.93 ± 3.81 and 62.0 ± 3.9%, respectively. Skin permeation of Cur was significantly (p < 0.05) improved when formulated into nanoemulgel since it showed the best steady state transdermal flux (SSTF) value (108.6 ± 3.8 µg/cm2·h) with the highest enhancement ratio (ER) (7.1 ± 0.2). In vivo anti-inflammatory studies proved that Cur-loaded nanoemulgel displayed the lowest percent of swelling (26.6% after 12 h). CONCLUSIONS: The obtained data confirmed the potential of the nanoemulgel dosage form and established the synergism of myrrh oil and Cur as an advanced anti-inflammatory drug.

5.
Nanomaterials (Basel) ; 10(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33008104

RESUMO

The purpose of this study was to fabricate biostable inorganic silver nanoparticles (AgNPs) using fresh peel (aqueous) extract of Benincasa hispida. A fast, robust, and eco-friendly approach was used for the synthesis of AgNPs, where bioactive components of peel extract of B. hispida acted as reducing and stabilizing agents. Synthesized AgNPs were characterized using a UV-Vis spectrophotometer, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and electron microscopy. The synthesized nanoparticles exhibited maximum absorption at 418 nm under the typical AgNPs surface plasmon resonance band range. They depicted a mean size of 26 ± 2 nm with a spherical shape. Their therapeutic prospective was determined by evaluating their antimicrobial and anticancer potential. The bio-synthesized silver nanoparticles exhibited strong antimicrobial activity with minimum inhibitory concentration (MIC 50) values of 14.5, 8.6, 6.063, and 13.4 µg/mL against Staphylococcus aureus (ATCC 25923), Micrococcus luteus (ATCC 14593), Escherichia coli (ATCC 25922), and Klebsiella pneumonia (ATCC 13883), respectively. The biosynthesized AgNPs showed potent in vitro cytotoxicity against human cervical cancer cell line with a half maximal inhibitory concentration (IC50) value of 0.066 µg/mL; however, no cytotoxic effect was observed on normal human primary osteoblasts cell line. This study explored B. hispida extract and confirmed its effectiveness as a promising source in producing AgNPs that could be employed for several therapeutic applications.

6.
Saudi Pharm J ; 28(2): 201-209, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32042259

RESUMO

Administration of almotriptan as an oral therapy is largely limited because of poor aqueous solubility and rather low bioavailability. The aim of present investigation was to formulate oral mucoadhesive film of almotriptan to improve the drug delivery and desired therapeutic effects. Placebo films (F1-F8) were prepared by varying the concentrations of Proloc 15 (7.5-15% w/v) and Eudragit RL 100/RS 100 (15-30% w/v) polymers. Physicomechanical and pharmaceutical characteristics of drug loaded films (FA1-FA4) were examined. Selected FA4 film was evaluated in vivo by assessing the pharmacokinetic profile and compared with oral therapy in rabbits. FA1-FA4 films exhibited excellent physicomechanical properties and rapid hydration. A biphasic and considerably greater drug release (p < 0.05) was observed in FA3 and FA4 films contain higher amount of hydrophilic polymer. The rate of permeation of almotriptan was found to be significantly higher in FA4 than FA3 film (p < 0.005). Fourier transform infrared spectral scan indicates no incompatibility exists between the drug and polymers used. Differential scanning calorimetry thermogram represents the evidence of almotriptan amorphization and molecular dispersion of it in the film. Scanning electron microscopy images shows that FA4 possess good morphological features and hence suitable for use in the buccal application. In vivo data demonstrated rapid and efficient absorption (p < 0.005) of almotriptan with greater AUC0-12 (>2 folds, p < 0.0001) by FA4 film as compared to oral (control). In general, the data established the potential of FA4 film to improve the therapeutic delivery of almotriptan and offers a promising option in migraine therapy.

7.
Pak J Pharm Sci ; 33(6(Supplementary)): 2847-2857, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33879446

RESUMO

Uropathogenic strains belonging to the Enterobacteriaceae family are considered one of factors for urinary tract infections, and type 1 pilus fimbrial adhesin (FimH) and beta lactamase CTX-M-15 play crucial roles in their pathogenesis and resistance. Thus, a promising approach is to explore dual-targeting therapeutic agents that act against both FimH and CTX-M-15. In the present study, active constituents of Nigella sativa were selected on the basis of significant activity against UTIs. Molecular docking was used to target active constituents of Nigella sativa to the active sites of FimH and CTX-M-15; these included thymoquinone, dithymoquinone, carvacrol, p-cymene, thymol, thymohydroquinone and longifolene. Dithymoquinone was found to be the most potent dual inhibitor, with binding energy of -7.01 and -5.38kcal/mol against CTX-M-15 and FimH, respectively; In addition, Dithymoquinone exhibited superior activity compared to positive controls avibactam and heptyl α-D-mannopyranoside. Further molecular dynamic simulation studies were carried out to assess the stability of dithymoquinone-target protein complexes via RMSD, Rg, SASA, hydrogen bond number, and RMSF analysis. Both protein-ligand complexes were conserved and attained equilibrium at around 2.0 to 2.5 ns during 10 ns runs. These results suggest that active constituents of Nigella sativa, particularly dithymoquinone, might represent a plausible therapeutic strategy against resistant uropathogenic bacteria.

8.
Pharmaceutics ; 11(11)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766305

RESUMO

Tissue repair and wound healing are complex processes that involve inflammation, granulation, and remodeling of the tissue. The potential of various statins including atorvastatin (ATR) to improve the wound healing effect was established. The aim of this study was to formulate and evaluate the efficacy of topical application of ATR-based nanoemulgel on wound healing. The prepared formulations (ATR gel, ATR emulgel, and ATR nanoemulgel) were evaluated for their physical appearance, rheological behavior, in vitro drug release and ex vivo drug permeation. The in vivo wound healing effect was evaluated in wound-induced rats. The prepared ATR gel formulations showed good physical properties and were comparable. The release profiles of drugs from gel, emulgel, and nanoemulgel were distinct. Skin permeation potential of ATR was significantly (p < 0.05) enhanced when formulated into nanoemulgel. In vivo wound healing studies showed that ATR nanoemulgel exhibited the highest percent wound contraction. Histopathological assessment showed marked improvement in the skin histological architecture after 21 days of ATR nanoemulgel treatment. In conclusion, the data demonstrated here signify the prospective of ATR nanoemulgel as an innovative therapeutic approach in wound healing.

9.
Drug Dev Ind Pharm ; 45(12): 1907-1914, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31621436

RESUMO

The current study aimed to formulate gelatin/sodium alginate nanoparticles utilizing BÜCHI nano spray dryer B-90. Nanoparticles possess many of the advantages including new routes of drug administrations and sustained release properties. Utilizing B-90 technology, metformin hydrochloride (MET) nanoparticles were successfully developed. Preformulation studies such as atomization head mesh size, flow rate, head temperature, polymer viscosity, and surface tension, were adjusted. Additionally, post-formulation characters such as particle size, flowability, surface scan, and dissolution profiles, were evaluated. Spray head (7 µm hole), flow rate (3.5 ml/min) and head temperature (120 °C) were optimized. Polymer viscosity was less than 11.2 cP with a surface tension less than 70.1 dyne/cm. Moreover, anti-diabetic effects of MET formulations were evaluated in streptozotocin-induced diabetic rats. Here, discrete, non-aggregated free-flowing nanoparticle powders with a particle size less than 850 nm were generated. Gelatin/sodium-alginate (1:3) produced nanoparticles were successfully sustained by the in vitro release profile of the drug. In vivo evaluations of the previous formula showed a significant reduction of blood glucose level over 24 h. In conclusion, Nano Spray Dryer B-90 (Büchi Labortechnik AG, Flawil, Switzerland) offers a promising technology for nanoparticles formulation as controlled drug delivery systems enhancing compliance of type-II diabetic patients.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Portadores de Fármacos/química , Composição de Medicamentos/instrumentação , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Alginatos/química , Animais , Glicemia/análise , Glicemia/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/induzido quimicamente , Composição de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos , Liberação Controlada de Fármacos , Gelatina/química , Humanos , Hipoglicemiantes/farmacocinética , Masculino , Metformina/farmacocinética , Nanopartículas/química , Tamanho da Partícula , Ratos , Estreptozocina/toxicidade
10.
Pharmaceutics ; 11(5)2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31083593

RESUMO

Nanoemulsion is one of the potential drug delivery strategies used in topical ocular therapy. The purpose of this study was to design and optimize a nanoemulsion-based system to improve therapeutic efficacy of moxifloxacin in ophthalmic delivery. Moxifloxacin nanoemulsions were prepared by testing their solubility in oil, surfactants, and cosurfactants. A pseudoternary phase diagram was constructed by titration technique and nanoemulsions were obtained with four component mixtures of Tween 80, Soluphor® P, ethyl oleate and water. An experiment with simplex lattice design was conducted to assess the influence of formulation parameters in seven nanoemulsion formulations (MM1-MM7) containing moxifloxacin. Physicochemical characteristics and in vitro release of MM1-MM7 were examined and optimized formulation (MM3) was further evaluated for ex vivo permeation, antimicrobial activity, ocular irritation and stability. Drug pharmacokinetics in rabbit aqueous humor was assessed for MM3 and compared with conventional commercial eye drop formulation (control). MM3 exhibited complete drug release in 3 h by Higuchi diffusion controlled mechanism. Corneal steady state flux of MM3 (~32.01 µg/cm2/h) and control (~31.53 µg/cm2/h) were comparable. Ocular irritation study indicated good tolerance of MM3 and its safety for ophthalmic use. No significant changes were observed in the physicochemical properties of MM3 when stored in the refrigerator for 3 months. The greater aqueous humor concentration (Cmax; 555.73 ± 133.34 ng/mL) and delayed Tmax value (2 h) observed in MM3 suggest a reduced dosing frequency and increased therapeutic efficacy relative to control. The area under the aqueous humor concentration versus time curve (AUC0-8 h) of MM3 (1859.76 ± 424.51 ng·h/mL) was ~2 fold higher (p < 0.0005) than the control, suggesting a significant improvement in aqueous humor bioavailability. Our findings suggest that optimized nanoemulsion (MM3) enhanced the therapeutic effect of moxifloxacin and can therefore be used as a safe and effective delivery vehicle for ophthalmic therapy.

11.
J Exp Orthop ; 4(1): 17, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28534321

RESUMO

BACKGROUND: To determine if tibial tunnel reaming during anatomic single-bundle anterior cruciate ligament (ACL) reconstruction using hamstring autograft can result in anterolateral meniscal root injury, as diagnosed by magnetic resonance imaging (MRI). METHODS: A case series of 104 primary anatomic single-bundle ACL reconstructions using hamstring autograft was retrospectively reviewed. Pre- and post-operative (>1 year) MRIs were radiologically evaluated for each patient, with a lateral meniscus extrusion > 3 mm at the level of the medial collateral ligament midportion on a coronal MRI, to establish anterolateral meniscal root injury. RESULTS: No patients presented radiological findings of anterolateral meniscal root injury in this case series. CONCLUSIONS: Examining a single-bundle ACL reconstruction technique using hamstring autograft that considered tibial tunnel positioning in the center of the tibial footprint, this case series found no evidence of anterolateral meniscal root injury in patient MRIs, even more than 1-year post-operation.

12.
Knee Surg Sports Traumatol Arthrosc ; 24(9): 2724-2728, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25416672

RESUMO

PURPOSE: To determine whether the bathing of an anterior cruciate ligament (ACL) autograft in vancomycin reduces the rate of infection following an ACL reconstruction. METHODS: Retrospective analysis of all ACL reconstructions over an 8-year period in two University Hospitals. In the initial 4-year period, all patients were operated on under classical antibiotic intravenous prophylaxis (group 1). Over the last 4-year period, this prophylaxis was supplemented with presoaking of the autograft (group 2). Presoaking was performed with sterile gauze previously saturated with a vancomycin solution (5 mg/ml). RESULTS: There were 810 and 734 patients in group 1 and 2, respectively. Fifteen cases of knee joint infections were identified in the series (0.97 %). All of these infections occurred in group 1, representing a rate of infection of 1.85 % in comparison with 0 % in group 2 (p < 0.001). CONCLUSIONS: Autograft presoaking with vancomycin in combination with classical intravenous antibiotic prophylaxis reduced the rate of knee joint infection following an ACLR in comparison with antibiotic prophylaxis alone. This technique could be of relevance in daily clinical practice to prevent infection after ACLR. LEVEL OF EVIDENCE: Case control study, retrospective comparative study, Level III.


Assuntos
Reconstrução do Ligamento Cruzado Anterior/métodos , Antibacterianos/administração & dosagem , Autoenxertos , Infecções Relacionadas à Prótese/prevenção & controle , Vancomicina/administração & dosagem , Ligamento Cruzado Anterior/efeitos dos fármacos , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior , Artrite Infecciosa/etiologia , Artrite Infecciosa/prevenção & controle , Artroscopia , Enxerto Osso-Tendão Patelar-Osso , Estudos de Casos e Controles , Humanos , Articulação do Joelho/cirurgia , Infecções Relacionadas à Prótese/etiologia , Estudos Retrospectivos , Risco , Transplante Autólogo
13.
Pharm Dev Technol ; 20(6): 652-61, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25069592

RESUMO

The aim of the current study was to investigate the effects of formulation parameters on the disintegration, water absorption and dissolution characteristics of cyclosporine A (CyA) loaded self-emulsifying drug delivery system (SEDDS) in an orodispersible compacts. Its taste masking efficiency was also attempted using an electronic tongue. ODTs were prepared by freeze-drying liquid SEDDS and synthetic amorphous silica suspension followed by direct compression. The influences of the compression forces and super-disintegrant were evaluated to optimize tablet characteristics. The liquid SEDDS was characterized by vesicular size of 48.5 nm, polydispersity index of 0.95, turbidity of 40.7 NTU and rapid CyA dissolution and emulsification rate. The results of micrometric studies demonstrated an acceptable flow, hardness and friability to indicate good mechanical strength of ODTs. The interaction and Pareto charts demonstrated a greater effect of low compression force to increase the porosity and facilitate the disintegration rather than the deformation action of the super-disintegrant. Super-disintegrant level was the most important factor affecting the dissolution parameter followed by the compression force then their interaction effect. Moreover, as indicated by Euclidean distance values and discrimination indices, the unpalatable taste and aversion taste of CyA to stimuli were masked in its optimized SEDDS incorporated ODTs.


Assuntos
Antifúngicos/administração & dosagem , Ciclosporina/administração & dosagem , Emulsões/química , Excipientes/química , Dióxido de Silício/química , Paladar , Antifúngicos/química , Química Farmacêutica/métodos , Ciclosporina/química , Liofilização/métodos , Dureza , Humanos , Porosidade , Solubilidade , Comprimidos/química
14.
AAPS PharmSciTech ; 16(2): 375-83, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25319057

RESUMO

Free-flowing proniosomal powders of acemetacin (AC) were prepared using the slurry method and maltodextrin as carrier. Positively charged proniosomes composed of 70:20:10 of Span 60/cholesterol (Chol)/stearylamine (SA), respectively, were successively compressed into tablets using direct compression method. The tablets were characterized for weight variability, friability, hardness, drug content uniformity, and dissolution properties. The in vivo evaluation of the prepared proniosomes (powder or tablet forms) after oral administration was investigated by the determination of AC and its active metabolite indomethacin (IND) in the blood of albino rabbits. Results indicated that the increase of Chol from 10% to 20% markedly reduced the efflux of the drug. Further Chol addition from 30% to 50% led to increased AC release rates. The proniosome tablets of AC showed greater hardness and disintegration time and less friability than AC plain tablets. The dissolution of proniosomal tablets indicated a lower drug release percentage compared to powdered proniosomes and AC plain tablets. The mean pharmacokinetic parameters of AC and IND from different formulations indicated increased t 1/2 and area under the curve (AUC) of both AC and IND for proniosomal tablets compared with both proniosomal powders and AC plain tablets. This study suggested the formulation of AC proniosomal powder into tablets to control and extend its pharmacologic effects.


Assuntos
Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Indometacina/análogos & derivados , Comprimidos/química , Comprimidos/farmacocinética , Administração Oral , Portadores de Fármacos/química , Dureza , Indometacina/química , Indometacina/farmacocinética , Polissacarídeos/química , Polissacarídeos/farmacocinética , Pós/química , Pós/farmacocinética , Solubilidade
15.
AAPS PharmSciTech ; 16(3): 645-55, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25501871

RESUMO

Pharmaceutical development was adopted in the current study to propose a pediatric rectal formulation of sulpiride as a substitute to the available oral or parenteral formulations in the management of Tourette syndrome (TS). The goal was to formulate a product that is easy to use, stable, and highly bioavailable and to achieve a rapid clinical efficacy. Towards this aim, sulpiride solid dispersion (SD) with tartaric acid at a weight ratio of 1:0.25 was incorporated into different suppository bases, namely witepsol W25, witepsol H15, witepsol E75, suppocire NA, suppocire A, glycerogelatin, and polyethylene glycols. The formulae were evaluated in vitro using different pharmacotechnical methods such as visual, melting, weight and content uniformities, drug release, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray diffraction (XRD) analyses. In vivo bioavailability was also assessed in rabbits to compare the bioavailability of either raw sulpiride-incorporated or its SD-incorporated witepsol H15-based suppositories to its oral suspension (reference). Sulpiride SD-incorporated witepsol H15 formulation showed acceptable in vitro characteristics with a bioavailability of 117% relative to oral dosing, which excel that in humans (27% after dosing of oral product). In addition, the proposed formula not only passed the 6-month stability study but also proposed a promising scale-up approach. Hence, it showed a great potential for pediatric product development to manage TS in rural areas.


Assuntos
Sulpirida/química , Sulpirida/farmacologia , Supositórios/química , Supositórios/farmacologia , Síndrome de Tourette/tratamento farmacológico , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Masculino , Polietilenoglicóis/química , Coelhos , Triglicerídeos/química , Difração de Raios X/métodos
16.
Eur J Pharm Sci ; 65: 130-8, 2014 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-25245006

RESUMO

2,4-Dichlorophenoxy acetic acid (2,4-D) is a well-known plant auxin which is widely used in plant tissue culture experiments as well as a weed killer and a herbicide. In this study, 2,4-D was rediscovered as a new anti-inflammatory agent through an in silico molecular modeling and docking studies along with drug formulation and in vivo anti-inflammatory inspection. The molecular modeling and docking studies indicated high affinity of 2,4-D toward COX-2 enzyme in a way similar to Ibuprofen, suggesting a higher anti-inflammatory activity. Molecular docking by both MOE 2013.08 and Leadit 2.1.2 revealed excellent binding pattern compared to some of well-known non-steroidal anti-inflammatory drugs. 2,4-D was formulated in different gel bases. In vitro drug release experiments were used to examine the best 2,4-D formula for in vivo studies. In vivo carrageenan-induced hind paw edema inflammatory model in rats was used to test the in silico finding. 2,4-D showed potential in vivo anti-inflammatory activity and significantly reduced the concentration of prostaglandin E2 in hind paw tissues in a way similar to Ibuprofen. These results may open the door to introduce a new anti-inflammatory molecule; especially that 2,4-D is a well-investigated regarding its toxicity and side effect.


Assuntos
Ácido 2,4-Diclorofenoxiacético/química , Ácido 2,4-Diclorofenoxiacético/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Animais , Carragenina/farmacologia , Química Farmacêutica/métodos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Reposicionamento de Medicamentos/métodos , Edema/tratamento farmacológico , Edema/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Ratos , Ratos Wistar
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