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Liquid sample delivery systems are used extensively for serial femtosecond crystallography at X-ray free-electron lasers (XFELs). However, misalignment of the liquid jet and the XFEL beam leads to the X-rays either partially or completely missing the sample, resulting in sample wastage and a loss of experiment time. Implemented here is an algorithm to analyse optical images using machine vision to determine whether there is overlap of the X-ray beam and liquid jet. The long-term goal is to use the output from this algorithm to implement an automated feedback mechanism to maintain constant alignment of the X-ray beam and liquid jet. The key elements of this jet alignment algorithm are discussed and its performance is characterized by comparing the results with a manual analysis of the optical image data. The success rate of the algorithm for correctly identifying hits is quantified via a similarity metric, the Dice coefficient. In total four different nozzle designs were used in this study, yielding an overall Dice coefficient of 0.98.
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INTRODUCTION: Severe open fractures continue to be a nightmare for orthopedicians even with use of more accepted line of treatment. Open fractures and infected non-union of femur bone are not infrequently seen in orthopedic wards as femur is the most common long bone injured. We present a case series of 14 such patients treated successfully with limb reconstruction system enabling recovery to pre-injury status and activities. CASE SERIES: The present study was done to access the role of limb reconstruction system in the management of open femur fractures and in infected non-union with modifications to meet the requirements of each case. We viewed the results of treatment of 14 cases of late presentation with complicated open femur fractures and infected non-unions. Average time of fixator removal was 4 months-24 months. Average follow-up duration was 18 months (range 6-36 months). Evaluation of results was based on ASAMI criteria. The excellent bone results were obtained in 85.72% of cases while 7.14% showed good and 7.14% were poor results. Excellent functional results were observed in 71.43% of cases and 28.57% of cases shows good and fair results. CONCLUSION: The use of limb reconstruction system is based on compression and distraction technique. It was found to be a simple and effective modality for open injuries in terms of enhanced union rate, rapid rehabilitation, and easy care of soft-tissue injury along with bone loss, thus avoiding multiple surgeries.
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INTRODUCTION: Incidence of open fractures of the long bones is increasing due to the increase in road traffic accidents (RTA) which leads to an increased incidence of complex non-unions of long bones. Patients are usually operated many times for fracture fixation (and healing) or to eradicate infection, which causes soft tissue scarring and devitalization of any surviving bone. OBJECTIVE: In this study, we assess the outcome of the Limb reconstruction system in tibial infected non-union and open tibial diaphyseal fracture with bone loss. METHOD: It is a prospective study conducted on 15 patients and patients included in this study having compound fractures of shaft tibia with bone loss classified by Gustilo-Anderson open fracture classification. With the defect in the distal tibia, proximal corticotomy 1.5 cm distal to the last screw in the proximal clamp and proximal to distal transports were done and vice versa. All patients were evaluated with the ASAMI scoring system into bone results and functional results. RESULTS: In the majority of patients, the injury was caused by road traffic accidents 80% of cases. Out of 15 cases, 2 belong to the upper 3rd, 9 cases belong to the middle 3rd and 4 cases belong to the lower 3rd of shaft tibia. The union time ranges from 4 to 11 months but the maximum union was achieved in 7-9 months in 8 (53.33%). Pin tract infection was reported in two (13.33%) patients who became better with regular dressing. Ankle stiffness was present in one case (6.67%), most probably due to improper physiotherapy.According to ASAMI Criteria excellent radiological results were present in 11 (73.33%) cases, good results were found in 4 (26.67) cases and excellent functional results were observed in 7 cases (46.67%) and good results were found in 8 (53.33%) cases. Infection was cured in all patients and did not recur till the last follow-up. CONCLUSIONS: Advantages of rail fixator include less invasive surgery, early weight-bearing, less infection, less blood loss, prevention of diffuse osteoporosis and atrophy, preservation of limb function, no need for bone grafting, correction of deformity during the process of healing, thus no need for a second surgery. Non-union, bone defect, and deformity can be corrected simultaneously. Hence, we recommend the use of this system (rail fixator) especially for infected non-union of long bones and compound fractures with bone loss.
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OBJECTIVES: This study reports our experience of the first 4-way kidney exchange transplant combined with desensitization in India, which allows increased access to living-donor kidney transplant for sensitized patients. MATERIALS AND METHODS: Four-way kidney exchange transplant procedures were approved by the ethics committee of our institution and the Organ Transplantation Authorization Committee of state governments of India (as per the Transplantation of Human Organs Act of India). The protocols conformed to Declaration of Istanbul principles and the ethical guidelines of the 1975 Helsinki Declaration. Written informed consent was obtained from patients, donors, and their guardians. RESULTS: In April 2016, our transplant team completed simultaneous 4-way kidney exchange transplant procedures without any medical (rejection and infections) or surgical complications. Reasons for being included for kidney exchange transplant were ABO incom-patible (2 recipients) and sensitization (2 recipients). All 4 recipients had stable graft function with no proteinuria and donor-specific antibody at 11-month follow-up on standard triple immunosup-pression. Patient and graft survival rates were both 100%. CONCLUSIONS: To the best of our knowledge, this is the first single-center report of 4-way kidney exchange transplant combined with desensitization from India. This procedure has the potential to expand living-donor kidney transplant in disadvantaged groups (eg, sensitized patients). Recipients who are hard to match due to high panel reactive antibody and difficult to desensitize due to strong donor-specific antibodies can receive a transplant with a combination of kidney exchange and desensitization. Our study suggests that 4-way kidney exchange transplant can be performed in developing countries (India) similar to that shown in programs in developed countries with team work, kidney exchange registry, and counseling.
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Incompatibilidade de Grupos Sanguíneos/tratamento farmacológico , Dessensibilização Imunológica/métodos , Doação Dirigida de Tecido , Rejeição de Enxerto/prevenção & controle , Acessibilidade aos Serviços de Saúde , Imunossupressores/administração & dosagem , Transplante de Rim/métodos , Doadores Vivos/provisão & distribuição , Sistema ABO de Grupos Sanguíneos/imunologia , Adulto , Incompatibilidade de Grupos Sanguíneos/imunologia , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Humanos , Índia , Isoanticorpos/sangue , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
In a living donor kidney transplantation (LDKT) dominated transplant programme, kidney paired donation (KPD) may be a cost-effective and valid alternative strategy to increase LDKT in countries with limited resources where deceased donation kidney transplantation (DDKT) is in the initial stages. Here, we report our experience of 300 single-centre KPD transplantations to increase LDKT in India. Between January 2000 and July 2016, 3616 LDKT and 561 DDKT were performed at our transplantation centre, 300 (8.3%) using KPD. The reasons for joining KPD among transplanted patients were ABO incompatibility (n = 222), positive cross-match (n = 59) and better matching (n = 19). A total of 124 two-way (n = 248), 14 three-way (n = 42), one four-way (n = 4) and one six-way exchange (n = 6) yielded 300 KPD transplants. Death-censored graft and patient survival were 96% (n = 288) and 83.3% (n = 250), respectively. The mean serum creatinine was 1.3 mg/dl at a follow-up of 3 ± 3 years. We credit the success of our KPD programme to maintaining a registry of incompatible pairs, counselling on KPD, a high-volume LDKT programme and teamwork. KPD is legal, cost effective and rapidly growing for facilitating LDKT with incompatible donors. This study provides large-scale evidence for the expansion of single-centre LDKT via KPD when national programmes do not exist.
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Transplante de Rim/métodos , Doadores Vivos , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Doação Dirigida de Tecido/estatística & dados numéricos , Feminino , Sobrevivência de Enxerto , Teste de Histocompatibilidade , Humanos , Índia/epidemiologia , Estimativa de Kaplan-Meier , Transplante de Rim/mortalidade , Transplante de Rim/estatística & dados numéricos , Doadores Vivos/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Obtenção de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adulto JovemRESUMO
PURPOSE: The aim of the present work was to improve rate of dissolution and processing parameters of BCS class II drug, chlorzoxazone using cogrinding technique in the presence of different excipients as a carrier. MATERIALS AND METHODS: The drug was coground with various carriers like polyethylene glycol (PEG 4000), hydroxypropyl methylcellulose (HPMC) E50LV, polyvinylpyrrolidone (PVP)K30, Kaolin and Neusilin US2 using ball mill, where only PEG 4000 improved dissolution rate of drug by bringing amorphization in 1:3 ratio. The coground mixture after 3 and 6 h was evaluated for various analytical, physicochemical and mechanical parameters. RESULTS: The analysis showed conversion of Chlorzoxazone from its crystalline to amorphization form upon grinding with PEG 4000. Coground mixture as well as its directly compressed tablet showed 2.5-fold increment in the dissolution rate compared with pure drug. Directly compressible tablets prepared from pure drug required a large quantity of microcrystalline cellulose (MCC) during compression. The coground mixture and formulation was found stable in nature even after storage (40°C/75% relative humidity). CONCLUSIONS: Cogrinding can be successfully utilized to improve the rate of dissolution of poorly water soluble drugs and hence bioavailability.
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The present investigation was aimed to develop self-nanoemulsifying tablets (SNETs) as novel nanosized solid oral dosage forms for Irbesartan (IRB). In the first part of the investigation, IRB-loaded self-nanoemulsifying drug delivery systems (SNEDDS) were developed using Capryol 90 - Cremophor RH40 - Transcutol P as three component (oil - surfactant - cosurfactant) SNEDDS system. On the basis of ternary phase diagram IRB-loaded SNEDDS were optimized by using Design of Experiments (DoE) and Principal component analysis (PCA) with amount of oil and surfactant: cosurfactant ratio (Km) as factors. The optimized batch of IRB-loaded SNEDDS comprised of 31.62% w/w of Capryol 90 as oil phase, 49.90% w/w Cremophor RH40 as surfactant and 18.48% w/w of Transcutol P as cosurfactant exemplified a mean globule size as 23.94 nm. Further, with an aim to provide enhanced patient compliance the optimized batch of liquid SNEDDS was transformed into SNETs by liquisolid compaction technique. Solid state characterization of IRB-loaded liquisolid mixtures revealed a decrease in the magnitude of crystallinity of IRB. The results of in vitro drug release study of optimized batch of IRB-loaded SNET illustrated a remarkable improvement in the dissolution rate as compared to marketed tablets (Avapro® 75). The results of in vivo pharmacokinetic study on Wister rats revealed 1.78-fold enhancement in oral bioavailability for IRB-loaded SNETs against marketed tablets. The present study proposed SNEDDS as one of the suitable approach for developing nanosized solid oral dosage forms of poorly water soluble drugs like Irbesartan.
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Compostos de Bifenilo/química , Compostos de Bifenilo/metabolismo , Emulsões/química , Emulsões/metabolismo , Nanopartículas/química , Comprimidos/química , Comprimidos/metabolismo , Tetrazóis/química , Tetrazóis/metabolismo , Administração Oral , Animais , Disponibilidade Biológica , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Irbesartana , Masculino , Nanopartículas/metabolismo , Óleos/química , Tamanho da Partícula , Ratos , Ratos Wistar , Solubilidade , Tensoativos/químicaRESUMO
BACKGROUND: The present study was aimed to develop and optimize in situ gel for the treatment of periodontal disease. MATERIALS AND METHODS: Temperature-sensitive in situ gel containing 0.1% w/v Chlorhexidine hydrochloride was formulated by cold method using different polymers. Preliminary study was carried out to optimize different types and concentration of polymers such as Poloxamer 188, Poloxamer 407, Gellan gum, and Carbopol 934P. Central composite design was employed for optimization of the effect of independent variables such as Poloxamer 407 and Carbopol 934P on responses such as gelation temperature, spreadability, cumulative percentage release at 2 h, and time for 50% drug release (t50 %). Each formulations were evaluated for clarity, pH, gelation temperature, spreadability, drug content, in vitro drug release, t50 %, and cumulative percentage drug release at 2 h. RESULTS: Results of evaluation parameters revealed that the drug release, gelation temperature was considerably decreased with increasing t50 % as the concentration of each polymer was increased. The desirability function was utilized to find out optimized formulation of the factorial design. Formulation F6 showed the highest overall desirability of 0.6283 and, therefore, this formulation was considered to be the optimized formulation. The % relative error was calculated, which showed that observed responses were in close agreement with the predicted values calculated from the generated regression equations. CONCLUSION: The clarity, pH, drug content of all formulations was found to be satisfactory. Further, all the formulations showed sustained drug release for a period of 6 h, which satisfied to treat periodontal disease.
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Poor mechanical properties of crystalline drug particles require wet granulation technique for tablet production which is uneconomical, laborious, and tedious. The present investigation was aimed to improve flow and mechanical properties of racecadotril (RCD), a poorly water soluble antidiarrheal agent, by a crystallo-co-agglomeration (CCA) technique. The influence of various excipients and processing conditions on formation of directly compressible agglomerates of RCD was evaluated. Principal component analysis and Box-Behnken experimental design was implemented to optimize the agglomerates with good micromeritics and mechanical properties. The overall yield of the process was 88-98% with size of agglomerates between 351 and 1214 µm. Further, higher rotational speed reduced the size of agglomerates and disturbed sphericity. The optimized batch of agglomerates exhibited excellent flowability and crushing strength. The optimized batch of RCD agglomerates was characterized by fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry and gas chromatography which illustrated absence of drug-excipient interaction with minimal entrapment of residual solvent. Hence, it may be concluded that both excipients and processing conditions played a vital role to prepare spherical crystal agglomerates of RCD by CCA and it can be adopted as an excellent alternative to wet granulation.
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Antidiarreicos/química , Excipientes/química , Tiorfano/análogos & derivados , Análise por Conglomerados , Cristalização , Composição de Medicamentos , Derivados da Hipromelose , Metilcelulose/análogos & derivados , Metilcelulose/química , Polietilenoglicóis/química , Álcool de Polivinil/química , Análise de Componente Principal , Projetos de Pesquisa , Solubilidade , Solventes/química , Talco/química , Resistência à Tração , Tiorfano/químicaRESUMO
BACKGROUND: Direct tabletting is a need of Pharmaceutical industries. Poor mechanical properties of drug particles require wet granulation which is uneconomical, laborious, and tedious. OBJECTIVE: Objective of this work was to study influence of various polymers/excipients on formation of directly compressible Crystallo-co-agglomerates (CCA) of water soluble drug Secnidazole (hydroxy-2-propyl)-1-methyl-2-nitro-5-imidazole), an antimicrobial agent. METHOD: Acetone-petroleum ether system was used to develop CCA of drug in the presence of polymers/excipients. Clarity of the supernatant was considered an endpoint for completion of agglomeration. The prepared CCA were subjected for topographic, micromeritic, mechanical, compressional, and drug release properties. RESULTS: The process yielded ~92 to 98% wt/wt CCA containing secnidazole with the diameter between 0.2 and 0.7 mm. CCA showed excellent flow, packability, compatibility, and crushing strength. Heckel plot showed lower σ(0) and higher tensile strength with lower elastic recovery (0.55-1.28%) of CCA. Dissolution profile of CCA was improved. Differential scanning calorimetry , fourier transform infra-red, and x-ray diffractometry results showed absence of drug-excipient interaction. DISCUSSION: Matrix beads were generated with uniform dispersion of crystallized drug. Excellent flow, packability, and compactability were due to sphericity of agglomerates. Higher crushing strength of CCA was an indication of good handling qualities. Lower σ(0), higher tensile strength, and lower elastic recovery indicated excellent compressibility of agglomerates. Improvement in dissolution profile was due to porous nature of CCA. CONCLUSION: Excipients and polymers can play a key role to prepare CCA, an excellent alternative to wet granulation process to prepare particles for direct compression.
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Antiprotozoários/química , Química Farmacêutica , Composição de Medicamentos/métodos , Excipientes/química , Metronidazol/análogos & derivados , Polímeros/química , Cristalização/métodos , Metronidazol/química , Tamanho da PartículaRESUMO
A highly water soluble antihypertensive drug, metoprolol tartrate (MT) was selected as a model drug for preparation ofmulti-walled carbon nanotubes (MWCNTs) impregnated ethyl cellulose (EC) microspheres with aim to increase encapsulation efficiency and sustained release rate. Carbon nanotubesdrug adsorbate (MWCNTs:MT) loaded EC microspheres were optimized by Central Composite Design of experiment. The effects of independent variables (MWCNTs:MT and EC:adsorbate) were evaluated on responses like entrapment efficiency (EE) and time required for 50% drug release (t50). Furthermore, desirability approach was adopted to select best batch. The results revealed improvement in encapsulation efficiency for MWCNTs:MTloaded EC microspheres. In vitro drug release study exhibited complete release form drug alone microspheres within 14 h while MWCNTs impregnated EC microspheres exhibited only 50-60 % drug release in 14 h.The optimized batch was further characterized by various instrumental analysis which endorse encapsulation of MWCNTs:MT adsorbate inside the matrix of EC microspheres which resulted in enhanced encapsulation and sustained effect of MT.
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PURPOSE: The purpose of the present investigation was to improve the flow and mechanical properties of racecadotril by a crystallo-co-agglomeration (CCA) technique. Direct tableting is a requirement of pharmaceutical industries. Poor mechanical properties of crystalline drug particles require wet granulation which is uneconomical, laborious, and tedious. MATERIALS AND METHODS: The objective of this work was to study the influence of various polymers/excipients and processing conditions on the formation of directly compressible agglomerates of the water-insoluble drug, racecadotril, an antidiarrheal agent. The agglomerates of racecadotril were prepared using dichloromethane (DCM)-water as the crystallization system. DCM acted as a good solvent for racecadotril as well as a bridging liquid for the agglomeration of the crystallized drug and water as the nonsolvent. The prepared agglomerates were tested for micromeritic and mechanical properties. RESULTS: The process yielded ~90 to 96% wt/ wt spherical agglomerates containing racecadotril with the diameter between 299 and 521 µ. A higher rotational speed of crystallization system reduces the size of the agglomerates and disturbs the sphericity. Spherical agglomerates were generated with a uniform dispersion of the crystallized drug. CCA showed excellent flowability and crushing strength. CONCLUSION: Excipients and processing conditions can play a key role in preparing spherical agglomerates of racecadotril by CCA, an excellent alternative to the wet granulation process to prepare intermediates for direct compression.
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Irbesartan (IRB) is an angiotensin II receptor blocker antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of poorly water-soluble IRB. The solubility of IRB in various oils was determined to identify the oil phase of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. The optimized SNEDDS formulation contained IRB (75 mg), Cremophor(®) EL (43.33%), Carbitol(®) (21.67%) and Capryol(®) 90 (32%). SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size and zeta potential. The optimized formulation of IRB-loaded SNEDDS exhibited complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug solution by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of IRB from SNEDDS compared with the pure drug solution. These results suggest the potential use of SNEDDS to improve dissolution and oral bioavailability of poorly water-soluble IRB.
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BACKGROUND AND AIM: Telmisartan (TEL) is an angiotensin II receptor blocker (ARB) antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of poorly water soluble TEL. MATERIALS AND METHODS: The solubility of TEL in various oils was determined to identify the oil phase of a SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. A SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size, zeta potential, pH, refractive index, and viscosity. RESULTS: The developed SNEDDS formulation contained TEL (20 mg), Tween(®) 20 (43.33%w/w), Carbitol(®) (21.67%w/w), and Acrysol(®) EL 135 (32%w/w). The optimized formulation of the TEL-loaded SNEDDS exhibited a complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug suspension by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of TEL from the SNEDDS compared with the pure drug suspension. CONCLUSIONS: These results suggest the potential use of the SNEDDS to improve the dissolution and oral bioavailability of poorly water soluble TEL.
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In the present study we investigated the effect of polyamidoamine (PAMAM) dendrimers on the aqueous solubility of aceclofenac. The aqueous solubility of aceclofenac was measured in the presence of dendrimers in distilled water. The effect of variables, such as pH condition, concentration, temperature and generation (molecule size) of dendrimer, has been investigated. Results showed that the solubility of aceclofenac in the dendrimer solutions was proportional to dendrimer concentration. The order in which the dendrimers increased the solubility at a constant pH condition was G3 > G0. The influence of dendrimer solution pH on the solubility enhancement of aceclofenac suggests that it involves an electrostatic interaction between the carboxyl group of the aceclofenac molecule and the amine groups of the dendrimer molecule. The solubility of aceclofenac was inversely proportional to the temperature of dendrimer solution.Different generation (G0 and G3) PAMAM dendrimers have the potential to significantly enhance the solubility of poor water-soluble drugs.
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A simple, sensitive, specific, spectrophotometric method was developed for the detection of Olmesartan medoxomil (OLM) in bulk and pharmaceutical formulations. The optimum conditions for the analysis of the drug were established. OLM was subjected to stress degradation under different conditions recommended by the International Conference on Harmonization (ICH). The samples so generated were used for degradation studies using the developed method. The λmax of the OLM was found to be 257 nm. The method exhibited high sensitivity, with linearity, in the 2 to 20 µg/ml range. The lower limit of detection and the limit of quantification were found to be 1.012 µg/ml and 3.036 µg/ml, respectively. All the calibration curves demonstrated a linear relationship between the absorbance and concentration, with the correlation coefficient higher than 0.99. The regression equation of the curve was Y = 0.0579x + 0.0006. The precision of the method was found to be 40.043 ± 0.067 against the label claim of 40 mg. The percentage recovery was found to be 101.32 ± 0.452. The sample solution was stable for up to two hours. Hence, it could be concluded that the proposed method would be suitable for the analysis of OLM in bulk and pharmaceutical formulations.