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5.
J Prosthet Dent ; 122(4): 389.e1-389.e8, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31547954

RESUMO

STATEMENT OF PROBLEM: Determination of interactive loading between a dental prosthesis and the host mandible is essential for implant prosthodontics and to preserve bone. PURPOSE: The purpose of this study was to develop and evaluate a robotic mastication simulator to replicate the human mastication force cycle to record the required interactive loading using specifically designed force sensors. MATERIAL AND METHODS: This robotic mastication simulator incorporated a Stewart parallel kinematic mechanism (PKM) controlled in the force-control loop. The hydraulically operated PKM executed the wrench operation, which consisted of the combined effect of forces and moments exhibited by the mastication process. Principal design features of this robotic simulator included PKM kinematic modeling, static force analysis to realize the masticatory wrench characteristics, and the architecture of its hydraulic system. Additionally, the design of a load-sensing element for the mandible and implant interaction was also incorporated. This element facilitated the quantification of the load distribution between implants and the host bone during the masticatory operation produced by the PKM. These loading tests were patient-specific and required separate artificial mandibular models for each patient. RESULTS: The simulation results demonstrated that the robotic PKM could replicate human mastication. These results validated the hydraulic system modeling for the required range of masticatory movements and effective forces of the PKM end-effector. The overall structural design of the robotic mastication simulator presented the integration of the PKM and its hydraulic system with the premeditated load-recording mechanism. CONCLUSIONS: The developed system facilitated the teeth-replacement procedure. The PKM accomplished the execution of mastication cycle involving 6 degrees of freedom, enabling any translation and rotation in sagittal, horizontal, and vertical planes. The mechanism can simulate the human mastication cycle and has a force application range of up to 2000 N. The designed load-sensing element can record interactive forces within the range of 200 N to 2000 N with fast response and high sensitivity to produce a robotic mastication simulator with custom-made modules.


Assuntos
Implantes Dentários , Procedimentos Cirúrgicos Robóticos , Força de Mordida , Análise do Estresse Dentário , Humanos , Mandíbula , Mastigação
6.
Pak J Pharm Sci ; 32(3 (Supplementary)): 1137-1143, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31326871

RESUMO

The aim of study was cross linking of high molecular weight chitosan nanoparticles containing 5-fluorouracil to improve dissolution rate and ultimately enhance its bioavailability by reverse emulsion/micelles method and cross-linking agent i.e. glutaraldehyde (GA 25% aqueous solution in water). The nature and outer morphologies were evaluated by scanning electron microscopy (SEM). Drug release models were functional to support way from cross linked NPs. Cross linking of 5-fluorouracil with glutaraldehyde improved dissolution rate. Mean dissolution time of 5-fluorouracil decreased significantly upon reverse emulsion/cross linking as encapsulated drug is protective and thermally stable within cross linked chitosan NPs. FTIR studies showed formation of intermolecular hydrogen bonding between 5-fluorouracil and GA-co-CHNPs. DSC studies indicated a less crystalline state of 5-fluorouracil in cross linking. SEM showed spherical nanoparticles with somewhat rough surface. 5-FU release followed Korsmeyer-Peppas model which indicate diffusion and dissociation control drug release from GA-co-CH-NPs. 5-FU cross linked chitosan nanoparticles can be safe and useful tool for other chemotherapeutic agents.

7.
Pak J Pharm Sci ; 32(3 (Supplementary)): 1137-1143, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31303582

RESUMO

The aim of study was cross linking of high molecular weight chitosan nanoparticles containing 5-fluorouracil to improve dissolution rate and ultimately enhance its bioavailability by reverse emulsion/micelles method and cross-linking agent i.e. glutaraldehyde (GA 25% aqueous solution in water). The nature and outer morphologies were evaluated by scanning electron microscopy (SEM). Drug release models were functional to support way from cross linked NPs. Cross linking of 5-fluorouracil with glutaraldehyde improved dissolution rate. Mean dissolution time of 5-fluorouracil decreased significantly upon reverse emulsion/cross linking as encapsulated drug is protective and thermally stable within cross linked chitosan NPs. FTIR studies showed formation of intermolecular hydrogen bonding between 5-fluorouracil and GA-co-CHNPs. DSC studies indicated a less crystalline state of 5-fluorouracil in cross linking. SEM showed spherical nanoparticles with somewhat rough surface. 5-FU release followed Korsmeyer-Peppas model which indicate diffusion and dissociation control drug release from GA-co-CH-NPs. 5-FU cross linked chitosan nanoparticles can be safe and useful tool for other chemotherapeutic agents.

8.
10.
Pak J Pharm Sci ; 32(2): 675-681, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31081782

RESUMO

Epilepsy remains a major chronic neurological disorder with significantly higher refractory seizure rate. Based on the folk medicine literature, we explored the anticonvulsant and antiepileptogenic activity of aqueous ethanolic extracts of Fumaria indica, Euphorbia lactea, Euphorbia helioscopia, Neurada procumbens, and Euphorbia nivulia. The acute anticonvulsant activity of the extracts was determined at different concentrations in different groups of Swiss albino mice. Among all the materials tested, the ethanolic extracts of Euphorbia nivulia (eth-EN) alone was found to exhibit concentration-dependent anticonvulsant effects when evaluated against the acute convulsant dose of Pentylenetetrazole (PTZ, 90mg/kg, s.c.). eth-EN extract at 100mg/kg i.p concentration showed maximum protection against the PTZ induced mortality (P<0.05). eth-EN (100mg/kg) treated animals also showed significant reduction in the progression of epileptogenesis (P<0.05) when tested against the PTZ-induced (50mg/kg s.c.) chemical kindling model of epilepsy. The FT-IR spectra of this extract showed both known and unknown spectral peaks from which the presence of the functional groups; i.e. aromatics, diketones, alkenes, carbonyls, carboxylic acids and amide compounds were confirmed. The unknown peaks strongly suggested the presence of novel compounds that may be responsible for its anticonvulsant and antiepileptogenic activity.

11.
Cochrane Database Syst Rev ; 4: CD005351, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30950507

RESUMO

BACKGROUND: Non-invasive positive pressure ventilation (NPPV) has been used to treat respiratory distress due to acute cardiogenic pulmonary oedema (ACPE). We performed a systematic review and meta-analysis update on NPPV for adults presenting with ACPE. OBJECTIVES: To evaluate the safety and effectiveness of NPPV compared to standard medical care (SMC) for adults with ACPE. The primary outcome was hospital mortality. Important secondary outcomes were endotracheal intubation, treatment intolerance, hospital and intensive care unit length of stay, rates of acute myocardial infarction, and adverse event rates. SEARCH METHODS: We searched CENTRAL (CRS Web, 20 September 2018), MEDLINE (Ovid, 1946 to 19 September 2018), Embase (Ovid, 1974 to 19 September 2018), CINAHL Plus (EBSCO, 1937 to 19 September 2018), LILACS, WHO ICTRP, and clinicaltrials.gov. We also reviewed reference lists of included studies. We applied no language restrictions. SELECTION CRITERIA: We included blinded or unblinded randomised controlled trials in adults with ACPE. Participants had to be randomised to NPPV (continuous positive airway pressure (CPAP) or bilevel NPPV) plus standard medical care (SMC) compared with SMC alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected articles for inclusion. We extracted data with a standardised data collection form. We evaluated the risks of bias of each study using the Cochrane 'Risk of bias' tool. We assessed evidence quality for each outcome using the GRADE recommendations. MAIN RESULTS: We included 24 studies (2664 participants) of adult participants (older than 18 years of age) with respiratory distress due to ACPE, not requiring immediate mechanical ventilation. People with ACPE presented either to an Emergency Department or were inpatients. ACPE treatment was provided in an intensive care or Emergency Department setting. There was a median follow-up of 13 days for hospital mortality, one day for endotracheal intubation, and three days for acute myocardial infarction. Compared with SMC, NPPV may reduce hospital mortality (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.51 to 0.82; participants = 2484; studies = 21; I2 = 6%; low quality of evidence) with a number needed to treat for an additional beneficial outcome (NNTB) of 17 (NNTB 12 to 32). NPPV probably reduces endotracheal intubation rates (RR 0.49, 95% CI 0.38 to 0.62; participants = 2449; studies = 20; I2 = 0%; moderate quality of evidence) with a NNTB of 13 (NNTB 11 to 18). There is probably little or no difference in acute myocardial infarction (AMI) incidence with NPPV compared to SMC for ACPE (RR 1.03, 95% CI 0.91 to 1.16; participants = 1313; studies = 5; I2 = 0%; moderate quality of evidence). We are uncertain as to whether NPPV increases hospital length of stay (mean difference (MD) -0.31 days, 95% CI -1.23 to 0.61; participants = 1714; studies = 11; I2 = 55%; very low quality of evidence). Adverse events were generally similar between NPPV and SMC groups, but evidence was of low quality. AUTHORS' CONCLUSIONS: Our review provides support for continued clinical application of NPPV for ACPE, to improve outcomes such as hospital mortality and intubation rates. NPPV is a safe intervention with similar adverse event rates to SMC alone. Additional research is needed to determine if specific subgroups of people with ACPE have greater benefit of NPPV compared to SMC. Future research should explore the benefit of NPPV for ACPE patients with hypercapnia.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Mortalidade Hospitalar , Edema Pulmonar/terapia , Adulto , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal/estatística & dados numéricos , Tempo de Internação , Ventilação não Invasiva , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Int J Biol Macromol ; 129: 233-245, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30738157

RESUMO

Oral drug delivery is natural, most acceptable and desirable route for nearly all drugs, but many drugs like NSAIDs when delivered by this route cause gastrointestinal irritation, gastric bleeding, ulcers, and many undesirable effects which limits their usage by oral delivery. Moreover, it is almost impossible to control the release of a drug in a targeted location in body. We developed thermo-responsive chitosan-co-poly(N-isopropyl-acrylamide) injectable hydrogel as an alternative for the gastro-protective and controlled delivery of loxoprofen sodium as a model drug. A free radical polymerization technique was used to synthesize thermo-responsive hydrogel by cross-linking chitosan HCl with NIPAAM using glutaraldehyde as cross-linker. Confirmation of crosslinked hydrogel structure was done by Fourier transform infrared spectra (FTIR). The thermal stability of hydrogel was confirmed through thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The scanning electron microscopy (SEM) was performed to evaluate the structural morphology of cross-linked hydrogel. To evaluate the rheological behavior of hydrogel with increasing temperature, rheological study was performed. Swelling and in vitro drug release studies were carried out under various temperature and pH conditions. The swelling study revealed that maximum swelling was observed at low pH (pH 1.2) and low temperature (25 °C) compared to the high range of pH and temperature and it resulted in quick release of the drug. The high range of pH (7.4) and temperature (37 °C) however caused controlled release of the drug. The in vivo evaluation of the developed hydrogel in rabbits demonstrated the controlled release behavior of fabricated system.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Quitosana , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Hidrogéis , Fenilpropionatos/administração & dosagem , Animais , Quitosana/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Hidrogéis/química , Concentração de Íons de Hidrogênio , Estrutura Molecular , Fenilpropionatos/farmacocinética , Coelhos , Reologia , Análise Espectral , Temperatura Ambiente , Células Vero , Viscosidade
14.
Curr Drug Deliv ; 16(4): 375-383, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30588882

RESUMO

PURPOSE: The purpose of this study was to develop a new PLGA based microsphere formulation aimed to release the olanzapine for the period of one month which will result in increased compliance. METHODS: Microspheres loaded with olanzapine were prepared using oil in water emulsion and solvent evaporation technique. The microspheres were characterized by surface morphology, shape, size, bulk density, encapsulation efficiency, and Fourier transform infrared spectrometry. In vitro release studies were performed in phosphate buffer at 37°C and in vivo studies were conducted on male Sprague- Dawley rats. RESULTS: The morphological results indicated that microspheres produced were having a smooth surface, spherical shape and the size in the range from 9.71 to 19.90 µm mean diameter. Encapsulation efficiency of olanzapine loaded microspheres was in the range of 78.53 to 96.12% and was affected by changing the ratio of lactic to glycolic acid in copolymer PLGA. The properties of PLGA and other formulation parameters had a significant impact on in vitro and in vivo release of drug from microspheres. In vitro release kinetics revealed that release of drug from microspheres is by both non-Fickian diffusion and erosion of PLGA polymer. In vivo data indicated an initial burst release and then sustained release depending on properties of PLGA, microsphere size, and bulk density. CONCLUSION: This study indicates that microsphere formulations developed with PLGA (75:25) and PLGA (85:15) have provided a sufficient steady release of drug for at least 30 days and can be potential candidates for 30-day depot injection drug delivery of olanzapine.


Assuntos
Antipsicóticos/administração & dosagem , Antipsicóticos/farmacocinética , Sistemas de Liberação de Medicamentos , Microesferas , Olanzapina/administração & dosagem , Olanzapina/farmacocinética , Poliglactina 910/administração & dosagem , Animais , Antipsicóticos/sangue , Injeções Subcutâneas , Cinética , Masculino , Olanzapina/sangue , Tamanho da Partícula , Poliglactina 910/química , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície
15.
J Ayub Med Coll Abbottabad ; 31(4): 527-529, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933304

RESUMO

BACKGROUND: The approval of direct acting anti-viral drugs has expanded the treatment access to all patient populations including elderly patients, who were previously neglected. We evaluated the response and tolerability of sofosbuvir plus daclatasvir in old age patients >60 year infected with HCV. METHODS: In this prospective observational study, 100 patients were enrolled and were divided into two groups: aged 60-69 (group A) and aged 70 and older (group B). All the patients were given sofosbuvir plus daclatasvir. Sustained virologic response at 12 weeks was the primary endpoint. Response and tolerability of treatment were analysed and compared between these patient groups. RESULTS: Hundred patients aged ≥60 years were treated with sofosbuvir plus daclatasvir. Sustained virologic response rate was 91% in group A (aged 60- 69 year) and 87.8% in group B (aged 70 year and older). No significant adverse effect was noted in both groups. No treatment discontinuation was encountered. CONCLUSIONS: Direct acting antiviral drug therapy is highly efficacious and safe for the treatment of HCV in older adults.

16.
J Mater Sci Mater Med ; 29(12): 191, 2018 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-30539389

RESUMO

The aim of the study was to synthesize and evaluate chitosan-based topical cross-linked hydrogel membranes of mupirocin for new pharmaceutical controlled release application. These cross-linked structured membranes were synthesized by modification of free radical polymerization. Low molecular weight (LMW) chitosan is cross-linked with 2-acrylamido-2-methylpropane sulfonic acid (AMPS) with a crosslinker N,N-methylenebisacrylamide (MBA). Hydrogel membranes were characterized by FTIR, DSC, TGA, SEM, Swelling behavior, sol-gel analysis, in vitro percent drug release at different pH, permeation across skin, ex vivo drug deposition study, irritation study and in vivo antibacterial activity of mupirocin loaded hydrogels. Developed membranes were spherical, adhesive and have good elastic strength. FTIR confirmed the cross-linking and formation of new structure having appropriate characteristics needed for controlled release delivery system. Drug release through rabbit's skin was evaluated by Franz diffusion cell and up to 6329.61 µg/1.5 cm2 was permeated and drug deposition in skin revealed significant retention up to 1224 µg/1.5 cm2. Formulated membranes were nonirritant to the skin as validated by Draize patch test. In surgical wound model, LMW chitosan-based hydrogel membranes showed prolong efficacy against bacterial infection caused by S. aureus. Enhanced retention of drug in skin demonstrated the good potential of topical delivery for skin bacterial infection.


Assuntos
Quitosana/química , Hidrogéis/química , Mupirocina/administração & dosagem , Administração Tópica , Animais , Antibacterianos/química , Materiais Biocompatíveis , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Membranas Artificiais , Polímeros/química , Coelhos , Dermatopatias , Testes de Irritação da Pele
17.
AAPS PharmSciTech ; 19(7): 3199-3209, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30171450

RESUMO

The purpose of the study was to synthesize and characterize a new form of topical membranes as chitosan-based hydrogel membranes for bacterial skin infections. The polymeric membranes were synthesized by modification in free radical solution polymerization technique. High molecular weight (HMW) chitosan polymer was cross-linked with monomer 2-acrylamido-2-methylpropane sulfonic acid (AMPS) through cross-linker N,N-methylenebisacrylamide (MBA). Mupirocin, an antibiotic, was used as model drug. The polymeric membranes were prepared in spherical form that found stable and elastic. Characterization of hydrogel membranes was performed by FTIR, SEM, DSC, TGA, swelling behavior, drug release, irritation study, and ex vivo drug permeation and deposition study. Structural and thermal studies confirmed the formation of new polymeric network with enhanced stability of hydrogel membranes. Permeation flux of drug from optimized formulation through rabbit's skin assessed by using Franz cell was up to 104.09 µg cm-2 h-1. Furthermore, hydrogel membrane has significant retention of drug in skin up to 2185 µg 1.5 cm-2. Draize patch test confirmed the synthesized hydrogels as non-irritant to skin. The preparation of a topical membrane with improved antibacterial activity within controlled release manner is desirable for the advancement and treatment of skin diseases.


Assuntos
Quitosana/química , Hidrogéis/química , Cicatrização/efeitos dos fármacos , Animais , Liberação Controlada de Fármacos , Membranas , Polímeros/química , Coelhos
18.
Pak J Pharm Sci ; 31(4): 1385-1392, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30033424

RESUMO

The main purpose of work was to formulate dexibuprofen loaded eudragit L-100 micro particles to acquire site specific delivery of dexibuprofen. Micro particles were formulated by an emulsion solvent evaporation method. Four formulations F1, F2, F3 and F4 having drug to polymer ratio 1:1, 1:2, 1:3 and 1:4, respectively were prepared and characterized. The rheological properties manifested that micro particles were worthy for further pharmaceutical exploitation. No notable drug polymer interaction was perceived in FT-IR spectroscopy. SEM micrographs showed rough surface of micro particles. The resulting micro particles had high entrapment efficiency greater than 70%. The in vitro dexibuprofen release at pH 1.2 exhibited poor drug release with less than 21% while at pH 6.8, 60% of the dexibuprofen was released up till 8th hour. The dexibuprofen release was modified by altering polymer concentration in the formulation. The subsequent micro particles were found to be best fit with zero-order release model. Micro particles were efficiently formulated with a focus to release the drug majorly in small intestine. With increase of polymer concentration enhanced entrapment efficiency and decelerated dexibuprofen release from the micro particles has been achieved. In vitro dexibuprofen studies verified the gastro-resistant property of micro particles thus qualify site specific release in gastrointestinal tract.


Assuntos
Portadores de Fármacos/química , Composição de Medicamentos/métodos , Ibuprofeno/análogos & derivados , Ácidos Polimetacrílicos/química , Química Farmacêutica , Liberação Controlada de Fármacos , Ibuprofeno/administração & dosagem , Ibuprofeno/química , Cinética , Tamanho da Partícula , Solubilidade , Propriedades de Superfície
19.
Drug Des Devel Ther ; 12: 349-364, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29503528

RESUMO

Background: The present work was conducted to prepare and evaluate transdermal patches with optimization of suitable polymeric blend of poly(meth) acrylates (Eudragit®) (Ammonio Methacrylate Copolymer Ph Eur) for sustained transdermal delivery of glimepiride. Method: Polymeric matrix transdermal films were prepared by using Ammonio Methacrylate Copolymer Ph Eur RL 100 and Ammonio Methacrylate Copolymer Ph Eur RS 100 as the film former, and dibutyl phthalate (30% w/w) as the plasticizer. Patches were characterized by physical appearance, thickness, weight variation, folding endurance, percentage erosion, swelling index, moisture content, and moisture uptake capacity. Fourier transform infrared spectroscopic studies and differential scanning calorimetry analysis of physical mixtures of contents were performed to identify any chemical and physical interaction between drug and excipients. Five different enhancers (isopropyl myristate [IPM], Span® 80, Tween® 20, eucalyptus oil, and limonene) were employed at three different concentrations of polymer (2%, 5%, and 10% w/w) in order to enhance permeation through rabbit skin. In vitro drug release studies were performed at pH 7.4, and scanning electron microscopy was conducted to elucidate surface morphology before and after the drug release. In vitro permeation studies through rabbit skin were performed on Franz diffusion cells and permeation kinetics followed the Higuchi model. Results: Results of in vitro permeation studies revealed that these enhancers not only increased drug release but also augmented the skin permeation of glimepiride. Conclusion: IPM was the most effective enhancer with the highest permeation flux of 51.763 µg/cm2/hr, and the enhancement effect of different enhancers on glimepiride permeation through rabbit skin was in the rank order of IPM > eucalyptus oil > Span® 80 > Tween® 20> limonene.


Assuntos
Sistemas de Liberação de Medicamentos , Excipientes/química , Hipoglicemiantes/administração & dosagem , Compostos de Sulfonilureia/administração & dosagem , Administração Cutânea , Animais , Varredura Diferencial de Calorimetria , Química Farmacêutica , Difusão , Liberação Controlada de Fármacos , Hipoglicemiantes/farmacocinética , Microscopia Eletrônica de Varredura , Polímeros/química , Coelhos , Pele/metabolismo , Absorção Cutânea , Espectroscopia de Infravermelho com Transformada de Fourier , Compostos de Sulfonilureia/química , Compostos de Sulfonilureia/farmacocinética , Adesivo Transdérmico
20.
Carbohydr Polym ; 181: 1169-1179, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29253946

RESUMO

Mixtures of polymer (chondroitin sulfate) and monomer (AMPS) in the presence of co-monomer (MBA) were employed for the production of hydrogels, with adjustable properties, following free radical copolymerization. The hydrogel's structural properties were assessed by FTIR, DSC, TGA, SEM and XRD which confirmed the development and stability of synthesized structure. The results from FTIR analysis showed that CS react with the AMPS monomer during the polymerization process and confirmed the grafting of AMPS chains onto CS backbone. The surface morphology of CS-co-poly(AMPS) hydrogels, as evident by SEM, corresponds to their improved swelling ability due to high porosity. Thermal analysis showed that crosslinking formed a stable hydrogel network which is thermally more stable than its basic ingredients. The effects of pH revealed an increasing trend in swelling with increasing concentration of either CS or AMPS. In addition, different modalities for drug loading were studied with respect to drug homogeneous distribution; loxoprofen sodium was employed as model drug and was loaded by swelling-diffusion method. In vitro drug release profiles and kinetics were assessed to confirm their reproducibility and reliability. Higuchi model is the best fit model to explain drug release from formed gels indicating diffusion-controlled release. Similarly, Korsmeyer-Peppas model yields remarkably good adjustments where release kinetics involves a combination of diffusion in hydrated matrix and polymer relaxation. Conclusively, CS-co-poly(AMPS) hydrogels could be a potential alternate to conventional dosage forms for controlled delivery of loxoprofen sodium for extended period of time.

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