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DPP-4 inhibitors have been shown to reverse amyloid deposition in Alzheimer's disease (AD) patients with cognitive impairment. Ocimum sanctum L. leaves reported the presence of important phytoconstituents which are reported to have DPP-4 inhibitory activity. To investigate the effects of petroleum ether extract of Ocimum sanctum L. (PEOS) in Intracerebroventricular streptozotocin (ICV-STZ) induced AD rats. ICV-STZ (3 mg/kg) was injected bilaterally into male Wistar rats, while sham animals received the artificial CSF. The ICV-STZ-induced rats were administered with three doses of PEOS (100, 200, and 400 mg/kg, p.o.) for thirty days. All experimental rats were subjected to behaviour parameters (radial arm maze task and novel object recognition test), neurochemical parameters such as GLP-1, Aβ42, and TNF-α levels, and histopathological examination (Congo red staining) of the left brain hemisphere. PEOS significantly reversed the spatial learning and memory deficit exhibited by ICV-STZ-induced rats. Furthermore, PEOS also shows promising results in retreating Aβ deposition, TNF α, and increasing GLP-1 levels. The histopathological study also showed a significant dose-dependent reduction in amyloid plaque formation and dense granule in PEOS -treated rats as compared to the ICV-STZ induced rats (Negative control). The results show that extract of Ocimum sanctum L. attenuated ICV-STZ-induced learning and memory deficits in rats and has the potential to be employed in the therapy of AD.

Albendazole belongs to BCS-II category whose systemic and local anthelmintic effectiveness is restricted due to its low water solubility–related dissolution properties. The present investigation was aimed to prepare salts of albendazole using various weak organic acids such as succinic acid, tartaric acid, benzoic acid, and citric acid as counterions. The solvent evaporation was used to prepare the salts. The results of differential scanning calorimetry, Fourier-transform infrared spectroscopy, and powder X-ray diffraction suggested the formation of a new crystalline solid phase due to reaction between ABZ and organic acids. The results of 1H NMR studies indicted the participation of protons attached to nitrogen atoms (N–-H +) in the salt formation process. A significantly higher amount of drug release was observed in in vitro dissolution study from all the prepared salts compared to a pure drug in 0.1 N HCl. Contrary to that, no significant improvement was observed in in vitro dissolution study performed in 6.8 pH phosphate buffer. The prepared novel salts successfully improved the saturation solubility and dissolution properties of albendazole.

Analytical methods are required to be developed at different stages of the pharmaceutical product life cycle. The concept of QbD can be extended to analytical method development known as analytical quality by design (AQbD). Quality by design is a systematic approach to development that begins with predefined objects and emphasizes product and process understanding and helps in the systematic approach to drug development. The concepts described in ICH Q8- Q11, commonly referred to as quality by design (QbD), have also been applied to the development of analytical methods. The benefits of applying the QbD principle to analytical methods include identifying and minimizing sources of variability that may lead to poor method robustness and ensuring that the method meets its intended performance requirements throughout the product and method lifecycle. Stress testing is a very important tool in pharmaceutical research and development to predict long-term stability. Stress studies should be performed in stability-indicating method development to understand drug behavior but also can be performed with method validation for regulatory filling predict stability and measure impurities. For determination of degradation pathways and structural elucidation of degradation produced, these stress testing are helpful. It is also used to select the storage condition and improve the manufacturing process of formulations.

The control of potentially mutagenic and carcinogenic impurities in pharmaceutical products is key importance in evaluating carcinogenic risk to humans. The recent discovery of nitrosamine impurities in some marketed pharmaceuticals has increased the risk of their mutagenic and carcinogenic potential. According to the International Agency for Research on Cancer (IARC), nitrosamine is the chemical classified as a probable human carcinogen. Nitrosamine impurities are known to be mutagenic and carcinogenic, very small exposure of these impurities can lead to cancer. These impurities may be produced and get incorporated into drug substances or drug products by a reagent, catalyst, solvent, or raw materials used in the process of manufacturing. The presence of nitrosamine impurities in angiotensin II receptor blocker (ARB) drugs containing tetrazole ring has caused worldwide product recalls. The various regulatory authorities have published the press release or notice regarding the control of these impurities with the interim limit. In 2007, the European medicines agency (EMA) suspended the marketing authorization of Viracept, because of the presence of elevated levels of ethyl methane sulfonate, in the drug product. Validated analytical methods are used to identify and quantify these impurities to the trace level at a given interim limit.

This study aimed to develop and optimize lutein-loaded solid lipid nanoparticles (Lu-SLN) for ocular delivery. The objective was to achieve the mean particle size of Lu-SLN less than 100 nm, sustain the drug release up to 8 h, and evaluate the corneal permeation parameters of the optimized batch. Lu-SLN were prepared by hot homogenization and cold dilution method. The Plackett-Burman screening design and 32 full factorial design were adopted sequentially to study the effect of various formulation and process variables, and further optimized with the help of desirability function. The statistical designs revealed that the amount of Gelucire® 44/14 and homogenization speed had a significant effect (P

The present study was aimed to develop and optimize linezolid loaded chitosan nanoparticles for pulmonary delivery. The objective was to achieve the mean particle size of nanoparticles less than 300 nm and the mass median aerodynamic diameter (MMAD) less than 5 μm and sustain the drug release up to 24 h. Linezolid nanoparticles were prepared by ionic gelation technique employing chitosan and sodium tripolyphosphate (STPP). A 32 full factorial design and desirability function were sequentially used to quantify the effect of independent variables on dependent variables and optimize the formulation. The preliminary studies suggested that the concentration of chitosan and concentration of STPP had an appreciable effect on mean particle size and percentage entrapment efficiency and hence were selected as independent variables in a factorial design. Statistical analysis of 32 full factorial design revealed that each independent variable had a significant effect (p

Objectives: To perform a systematic review of otolaryngologic presentation rates to emergency department settings before and after lockdown due to the COVID-19 pandemic. Sources: PubMed, Scopus, and CINAHL. Methods: A systematic search was conducted following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses) for studies describing otolaryngologic presentations to emergency department and rapid access clinic settings both in the before-lockdown and after-lockdown periods. The start of after-lockdown period varied based on initiation of lockdown, ranging from March 1st to June 1st of 2020 across general emergency department studies. Results: A total of 14 studies were included in this review. About 10 were general emergency departments, 3 were specifically pediatric emergency departments, and 1 study focused on the geriatric population (>65 years). A total of 13 790 patients were included, with 9446 in the before-lockdown period (68.5%) and 4344 in the after-lockdown period (31.5%). Meta-analysis of proportions for otolaryngologic presentations across general emergency departments was performed. Comparison of weighted proportions found significant differences between before-lockdown and after-lockdown presentation rates for infectious etiologies, tonsillitis specifically, foreign bodies, non-infectious airway issues, and epistaxis among these studies. Conclusions: The increased proportions of various non-infectious presentations (eg, epistaxis, foreign bodies, and airway issues) following lockdown might be associated with proportional decreases in infectious pathologies, given decreased social contact to prevent SARS-CoV-2 transmission. Overall, it is important for otolaryngologists to recognize what presentations might more commonly be seen and require evaluation and potential intervention in light of a global pandemic.

Lipid-based emulsion system - a subcategory of emulsion technology, has emerged as an enticing option to improve the solubility of the steadily rising water-insoluble candidates. Along with enhancing solubility, additional advantages such as improvement in permeability, protection against pre-systemic metabolism, ease of manufacturing, and easy to scale-up have made lipid-based emulsion technology very popular among academicians and manufacturers. The present article provides a comprehensive review regarding various critical properties of lipid-based emulsion systems, such as microemulsion, nanoemulsion, SMEDDS (self microemulsifying drug delivery system), and SNEDDS (self nanoemulsifying drug delivery system). The present article also explains in detail the similarities and differences between them, the stabilization mechanism, methods of preparation, excipients used to prepare them, and evaluation techniques. Subtle differences between nearly related terminologies such as microemulsion and nanoemulsion, SMEDDS, and SNEDDS are also explained in detail to clarify the basic differences. The present article also gives in-depth information regarding the chemical structure of various lipidic excipients, various possible chemical modifications to modify their inherent properties, and their regulatory status for rational selection.

Purpose: Postoperative radiation therapy (RT) is commonly used for World Health Organization grade II-III intracranial ependymoma. Clinicians generally aim to begin RT ≤5 weeks after surgery, but postoperative recovery and need for second look surgery can delay the initiation of adjuvant therapy. On ACNS 0831, patients were required to enroll ≤8 weeks after initial surgery and begin adjuvant therapy within 3 weeks after enrollment. The purpose of this study was to determine the optimal timing of RT after surgery. Methods and Materials: The National Cancer Database was queried for patients (aged 1-39 years) with localized World Health Organization grade II-III intracranial ependymoma treated with surgery and postoperative RT. Overall survival (OS) curves were plotted based on RT timing (≤5 weeks, 5-8 weeks, and >8 weeks after surgery) and were compared by log-rank test. Factors associated with OS were identified by multivariate analysis. After 2009, complete data were available on whether patients underwent gross total resection or subtotal resection. Planned subset analysis was performed to examine the effect of RT timing on OS in patients with known extent of resection. Results: In the final analytical data set of 1043 patients, no difference in 3-year OS was observed in patients who initiated RT ≤5 weeks, 5 to 8 weeks, and >8 weeks after surgery (89.8% vs 89.1% vs 88.4%; P = .796). On multivariate analysis, grade III tumors (hazard ratio, 2.752; 95% confidence interval, 1.969-3.846, P < .001) and subtotal resection (hazard ratio, 2.253; 95% confidence interval, 1.405-3.611, P < .001) were significantly associated with reduced OS. Timing of RT, total RT dose, age, and other factors were not significant. These findings were affirmed in the subset of patients treated between 2010 and 2016, when extent of resection was routinely recorded. Conclusions: Delayed postoperative RT was not associated with inferior survival in patients with intracranial ependymoma. Delayed RT initiation may be acceptable in patients who require longer postoperative recovery or referral to an appropriate RT center, but should be minimized whenever practical.

Background: Levofloxacin has been recommended by WHO for the treatment of pulmonary tuberculosis and inhalable delivery of levofloxacin can be advantageous over conventional delivery. Objective: This study aimed to develop and optimize inhalable levofloxacin loaded chitosan nanoparticles (LCN). The objective was to achieve the mean particle size of LCN less than 300nm, sustain the drug release up to 24 h and achieve MMAD of LCN of less than 5μm. Methods: LCN were prepared by ionic gelation of chitosan with sodium tripolyphosphate (STPP) and subsequent lyophilization. A Plackett Burman screening design, 32 full factorial design, and overlay plots were sequentially employed to optimize the formulation. The mean particle size, % entrapment efficiency, in vitro drug release, and minimum inhibitory concentration were all evaluated. Results: The Pareto chart from the Placket Burman screening design revealed that the concentrations of chitosan and STPP was found to be significant (p < 0.05). Further analysis by 32 full factorial design revealed that F-ratio for each model generated was found to be greater than the theoretical value (p < 0.05), confirming the significance of each model. Conclusion: The optimized formulation showed a mean particle size of 171.5 nm, sustained the drug release up to 24 h in simulated lung fluid, and revealed MMAD of 3.18 μm, which can confirm delivery of the drug to the deep lung region. However, further in vivo studies are required to design a suitable dosage regimen and establish the fate of nanoparticles for safe and efficacious delivery of the drug.

PURPOSE/OBJECTIVES The prognosis for glioblastoma in elderly patients is poor; randomized trials have demonstrated comparable survival following adjuvant radiotherapy (RT) using conventional or hypofractionation. We used the National Cancer Database (NCDB) to measure trends in the use of hypofractionated RT in glioblastoma patients 70 years of age and older. MATERIALS AND METHODS The NCDB was queried for elderly glioblastoma patients treated with a known RT dosing schema from 2004-2015 (n=10,089 patients). Adjusted logistic regression was used to assess the association of treatment year with the annual percentage of patients who received hypofractionated RT (including 40-45 Gy/15 fractions, 34 Gy/10 fractions, or 25 Gy/5 fractions). Average annual percentage change (AAPC) was compared to determine if a significant change occurred in the use of hypofractionated RT during this period. Multivariable regression was used to determine factors associated with the use of hypofractionated RT. RESULTS Use of hypofractionated RT was stable between 2.5-3.3% from 2004-2008 and then monotonically increased to 22.2% by 2015 (p< 0.001). The AAPC in the use of hypofractionated RT was +29.6% per year (p< 0.001), with a corresponding decline in conventional fractionation over this period. No significant change was observed in palliative dosing schema or the use of stereotactic radiosurgery. On logistic regression, age, treatment at an academic center, Charlson Deyo score ≥2, and treatment year were significantly associated with utilization of hypofractionated RT. In this dataset, 24.8% of patients who received either conventional or hypofractionated RT died within 3 months of beginning RT. CONCLUSIONS During 2008-2015, an increasing number of elderly patients with glioblastoma received hypofractionated RT. Hypofractionated RT should be considered in elderly patients to shorten the time spent receiving medical care during the final months of life. Attention to hospice care is also important, especially in those with brief expected survival who may derive limited benefit from RT.

Objectives The aim of this study was to develop and optimize levofloxacin loaded PLGA nanoparticles (LN) for pulmonary delivery employing screening and experimental design and evaluate their in-vitro and in-vivo performance. The objective was to achieve Mass Median Aerodynamic Diameter (MMAD) of LN of less than 5μm, sustain the drug release up to 120 h and a higher AUC/MIC at the site of action. Methods LN were prepared by modified emulsion solvent evaporation technique employing high speed homogenization, probe sonication and subsequent lyophilization. Key Findings The Pareto chart from Placket Burman screening design revealed that homogenization speed and amount of PLGA were found to be significant (P < 0.05). Further analysis by 3 full-factorial design revealed that F-ratio was found to be far greater than the theoretical value (P < 0.05) for each regression model. Conclusion The optimized formulation with desirability value 0.9612 showed mean particle size of 146 nm, MMAD of 4.40 μm and sustained the drug release up to 120 h in simulated lung fluid. Augmentation in Cmax (1.71-fold), AUC 0-∞ (5.46-fold), Mean Residence Time (6.64-fold) and AUC/MIC (6.21-fold) of LN through pulmonary route was found to significantly higher (P < 0.05) than levofloxacin (p. o.).

Dual-energy CT (DECT) can improve the accuracy of myocardial perfusion CT with projection-based monochromatic (DECT-MCE) and quantification of myocardial iodine in material decomposition (DECT-MD) reconstructions. However, evaluation of multiple reconstructions is laborious and the optimal reconstruction to detect myocardial perfusion defects is unknown.Left ventricular (LV) phantoms with artificial perfusion defects were scanned using DECT and single energy cardiac computed tomography angiography (SECT). Reconstructions of DECT-MCE at 40, 70, 100 and 140 keV, DECT-MD pairs of water, iodine, iron and fat, and SECT were evaluated using a 17-segment myocardial model. The diagnostic performance of each reconstruction was calculated on a per-segment basis and compared across DECT reconstructions.Over 34 phantoms with artificial perfusion defects were found in 64/578 (11%) of segments, the sensitivity of DECT-MCE at 40, 70, 100, and 140 keV was 100% (95% confidence interval (CI): 93-100), 100% (95% CI: 93-100), 71% (95% CI: 56-83), and 25% (95% CI: 14-40), respectively, with a significant decline between 70 keV and 100 keV (p 0.001). The specificity of DECT-MCE was 100% at all energies (95% CI: 99-100). As a group, the DECT-MD iodine background reconstructions had significantly lower sensitivity than the remaining modes (2.1% [95% CI, 0.05-11.1], vs. 100% [95% CI, 92.6-100], p 0.001). Specificity of all material pair modes remained 100%.Using LV phantom models, the approach with the best sensitivity and specificity to assess myocardial perfusion defects with DECT are reconstructions of DECT-MCE at 40 or 70 KeV and DECT-MD without iodine background.

The present study is aimed to design and develop linezolid loaded PLGA nanoparticles (LZ NPs) for treatment of pulmonary tuberculosis. The objective was to prepare LZ NPs with a mean particle size below 300 nm and having Mass Median Aerodynamic Diameter (MMAD) less than 5 μm and sustain the drug release up to 120 h. The LZ NPs were prepared by modified emulsion solvent evaporation method using high-speed homogenization, sonication and subsequent lyophilization. Preliminary studies revealed that dimethyl sulphoxide was a suitable organic phase while α – phosphatidylcholine and PVP S 630 D were the suitable stabilizers for stabilizing the nanoparticles. A 32 full factorial design revealed that both process variables namely homogenization time and homogenization speed had a significant effect (p

INTRODUCTION Postoperative radiotherapy is commonly given for WHO Grade 2–3 intracranial ependymoma. Clinicians generally aim to begin radiotherapy ≤5 weeks following surgery, but the optimal timing remains uncertain. METHODS The National Cancer Database was queried for patients (age ≤39 years) with localized WHO Grade 2–3 intracranial ependymoma treated with surgery and postoperative radiotherapy. Multivariable logistic regression was used to identify factors associated with delayed postoperative radiotherapy, defined as starting >8 weeks after surgery. Overall survival (OS) curves were plotted based on radiotherapy timing (≤5 weeks, 5–8 weeks, and >8 weeks after surgery) and compared by log-rank test. Multivariate analysis (MVA) was used to identify factors associated with OS. RESULTS In the final analytic set of 1,043 patients, age ≥21 years (OR 2.07, 95% CI 1.56–2.74) and WHO Grade 2 tumors (OR 1.41, 95% CI 1.08–1.85) were significantly associated with delayed time to adjuvant radiotherapy. No difference in 3-year OS was observed in patients who initiated radiotherapy ≤5 weeks, 5–8 weeks, and >8 weeks after surgery (89.8% vs. 89.1% vs. 88.4%; p= 0.796). On MVA, anaplastic histology (HR 2.414, 95% CI 1.784–3.268, p CONCLUSION Delayed postoperative radiotherapy was not associated with inferior survival in patients with intracranial ependymoma, suggesting delayed radiotherapy initiation may be considered in patients requiring longer postoperative recovery or referral to an appropriate radiotherapy center.

Alcohol misuse is a common social issue related to the central nervous system. Electroencephalogram (EEG) signals are used to depict electrical activities of the brain. In the proposed study, a new computer-aided diagnosis (CAD) has been developed to recognize alcoholic and normal EEG patterns, accurately. In this paper, we present an automatic system for the classification of normal and alcoholic EEG signals using orthogonal wavelet filter bank (OWFB). First, we derive sub-bands (SBs) of EEG signals. Then, we compute logarithms of the energies (LEs) of the SBs. The LEs are employed as the discriminating features for the separation of alcoholic and normal EEG signals. A supervised machine learning algorithm called K nearest neighbor (KNN) has been employed to classify normal and alcoholic patterns. The proposed model has yielded very good classification results. We have achieved a classification accuracy (CA) of 94.20% with tenfold cross-validation (CV).

The present investigation was carried out to design, optimize, and evaluate lurasidone hydrochloride nanocrystals for improving its solubility and dissolution characteristics. Nanocrystals were prepared by media milling technique using zirconium oxide beads with 0.1 mm diameter. Various stabilizers, viz. poloxamer 188, PVP K30, SLS, HPMC E15, and PVP S 630 D, were evaluated to stabilize the nanocrystals. The Pareto chart obtained through Plackett-Burman screening design revealed that HPMC E 15 showed the highest standardized effect (p value

This paper proposes an adaptive integral back-stepping control scheme for tracking control of 2-DOF (Degree of Freedom) helicopter. The helicopter is an important model from the control prospective due to its nonlinear behavior, highly cross coupling effects and instability in open loop. Classical control methods (PI, PD and PID Controllers) and baseline controllers with a linear quadratic regulator (LQR) are unable to handle parametric uncertainties and unmodeled dynamics. The key advantage of the proposed scheme is that it gives robustness to parameter uncertainties and unmodeled dynamics. An adaptive update can provide system robustness through estimation of parameters and model uncertainties. Simulation and Experimental results support the expected effectiveness of the proposed adaptive integral backstepping scheme for tracking as compared to the baseline controller (LQR) in presence of uncertainties.

The financial performance of a marine energy project is based on assumptions with significant uncertainty. To fully appraise the risk, potential investors require an understanding of the likelihood of deviations from the assumed most likely case for a project’s financial performance. A Monte Carlo Analysis (MCA) model with flexible user defined uncertainty definitions for all inputs is developed for this study. A realistic tidal energy project is used as a case study to compare the central, optimistic and pessimistic Levelised Cost of Energy (LCOE) and Internal Rate of Return (IRR) values derived using commonly used deterministic methods and the probabilistic MCA model. The improvement in decision support due to the probabilistic analysis is shown and the possibility for misinterpreting the deterministic results in highlighted. Two sensitivity analysis methods are employed to identify key risks and emphasise the need to use the most appropriate method for the type of analysis being conducted. Finally, the significance of some commonly ignored parameters is tested and shown to be important for accurately appraising the investment risk in a real project. Thus this paper provides guidance and tools to help investors make informed decisions with confidence.

The aim of this study is to improve the bioavailability of a poorly water-soluble drug glibenclamide (GLB), by preparing drug nanocrystals using wet milling by zirconia beads. To improve the dissolution characteristics, various formulation and process variables were identified and optimized by employing a 32 factorial design at two stages. Based on preliminary studies, the formulation variables selected were polymer-to-drug ratio and surfactant-to-drug ratio and the process variables selected were milling speed and milling time. The particle size, zeta potential, saturation solubility, and percentage drug released at 10 min were selected as dependent variables at both stages. F ratio suggested that the predetermined response parameters were significantly dependent on the independent variables. An optimum desirability of 0.9925 was achieved using response profiler by Statistica® 8.0. The optimized formulation prepared as per levels obtained through desirability showed a close agreement between the predicted and expected values. X-ray diffraction studies concluded that the crystallinity of prepared nanocrystals was intact and the increased dissolution could be ascribed to conversion of unmilled drug to nanocrystals. In vivo studies carried out on male Wistar rats suggested a higher AUEC(0–8h) for GLB nanocrystals as compared to pure GLB which could be ascribed to significant improvement of release from GLB nanocrystals as compared to pure GLB. It could be concluded that prepared GLB nanocrystals showed better bioavailability as compared to pure GLB and could offer improved drug therapy.

This study is to improve the dissolution characteristics of a poorly water-soluble drug glibenclamide (GLB), by preparing nanoparticles through liquid anti solvent precipitation. A Plackett–Burman screening design was employed to screen the significant formulation and process variables. A total of 12 experiments were generated by Minitab® 16 for screening 5 independent variables namely the amount of poloxamer 188 (PX) (X1), amount of PVP S 630 D (PD) (X2), solvent to antisolvent volume ratio (S/AS) (X3), amount of GLB (X4) and speed of mixing (X5). Mean particle size (Y1), saturation solubility (Y2) and % dissolution efficiency (%DE5min) (Y3) were selected as response variables. All the regression models yielded a good fit with high determination coefficient and F value. The Pareto chart depicted that all the independent variables except the amount of GLB had a significant effect (p

Ezetimibe (EZE), a water insoluble drug, depicts variable bioavailability. The objective of the present investigation was to improve dissolution characteristics of EZE, which might offer improved bioavailability. The solid dispersions were prepared using poloxamer 407 (L 127) and polyvinyl pyrrolidone by melt and solvent method, respectively. Phase solubility studies indicated linear relationship between drug solubility and carrier concentration. In vitro release studies revealed improvement in the dissolution characteristics of EZE in solid dispersions. Solid dispersion with L 127 gave better rate and extent of dissolution. The best fit model indicating the probable mechanism of drug release from solid dispersions was found to be Korsemeyer–Peppas. The results of characterization of solid dispersions by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction revealed reduction in drug crystallinity which might be responsible for improved dissolution properties. The tablets of solid dispersion, containing L 127 prepared by direct compression, exhibited better drug release as compared to marketed formulation.

Identification of seizure using electroencephalogram (EEG) signal is crucial to detect diseases like epilepsy. Manual epilepsy detection is time consuming and prone to errors. Various techniques have been developed to get quick and accurate results for epilepsy detection. We propose a novel approach to detect epileptic seizure using bi-orthogonal wavelet filters. The bi-orthogonal wavelet filters divide the EEG signal into different sub-bands. Then different features, i.e., Shannon entropy (ShEn), Renyi entropy (RenEn), fractal dimension (FD), energy and fuzzy entropy (FE) are extracted from the sub-bands. The [Formula: see text]-values of the features are used to evaluate the discriminating ability of the features. These features are given as input to the support vector machine (SVM). The EEG signals are then classified into the following classes: (i) normal versus seizure, (ii) seizure-free versus seizure, (iii) normal versus seizure-free versus seizure, and (iv) normal versus seizure-free. We have used two independent datasets: a public dataset for training and validation of the model, and a private dataset for evaluating the model’s performance. The ten-fold cross-validation method is used here to reduce the chances of over fitting. The SVM classifier yielded 100% accuracy in discriminating both seizure-free and normal patients for public dataset, and inter-ictal and ictal for private dataset. It also gave very good classification accuracies for the other classification problems for both the datasets. The proposed method is ready for the clinical trial to be tested with huge databases before the actual practical usage.

The aim of this investigation was to improve the dissolution properties of the water-insoluble drug ezetimibe (EZE) and potentially improve bioavailability. A combination of melt and adsorption techniques was employed for the preparation of solid dispersions. PEG 4000, PEG 6000, and Gelucire 44/14 were used as hydrophilic carriers, and lactose monohydrate was used as an adsorbent. Phase solubility curves are of AL type, indicating a linear relationship between drug solubility and carrier concentration. Dissolution studies reveal an improvement of in vitro drug release. Mathematical modeling indicates that drug release data are best described by the Korsmeyer–Peppas model, with Fickian diffusion as the possible drug-release mechanism. Physicochemical characterization of solid dispersions by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) suggests a reduction in drug crystallinity following dissolution enhancement. Hence, the present investigation reveals that the dissolution characteristics of EZE could be ameliorated in a solid dispersion. INTRODUCTION Out of several methods employed to enhance the dissolution characteristics of poorly water-soluble drugs, solid dispersion techniques have been widely reported by various researchers with encouraging results for different drugs. However, a solid dispersion system is somewhat limited by poor flow properties and poor stability. The processing variables of solid dispersions can be improved by the addition of adsorbent in the solid dispersion melt, thereby increasing the effective surface area of the drug leading to improved dissolution (1, 2). Various carriers have been used to prepare solid dispersion systems; among those, polyethylene glycols (PEG) and Gelucire 44/14 are employed in the present investigation. PEGs are used because of their low toxicity, high water solubility, low cost, and availability in a wide range of molecular weights. Gelucire 44/14 is a mixture of glycerol and PEG 1500 esters of long-chain fatty acids. The suffixes 44 and 14 refer to its melting point and its hydrophilic/lipophilic balance (HLB), respectively. PEG 4000, PEG 6000, and Gelucire 44/14 have been used successfully to improve the dissolution properties of poorly water-soluble drugs by preparing solid-dispersion systems (3–5). However, the solid dispersions prepared with these carriers are sticky and difficult to handle. Hence, they must be used in amalgamation with an adsorbent to improve their flow properties. Ezetimibe (EZE), 1-(4–fluorophenyl) –3(R)-[3-(4–fluorophenyl) –3(S) hydroxy-propyl]-4(S)-(4-hydroxyphenyl)-2azetidinone, is the first lipid-lowering drug that inhibits the intestinal uptake of cholesterol without affecting the absorption of fat-soluble nutrients. It is indicated as a monotherapy or in combination with statins for the treatment of hypercholesterolemia (6). EZE, being practically insoluble in water, exhibits a low dissolution profile in gastrointestinal fluids with variable bioavailability. Thus, researchers have investigated different approaches to ameliorate the dissolution characteristics of EZE (7–9) and optimize bioavailability with a less variable pharmacokinetic profile. In the present investigation, an attempt was made to improve the dissolution properties of EZE by preparing free-flowing solid dispersions. A combination of solid dispersion and adsorption techniques was employed for the preparation of the solid systems, using lactose monohydrate as adsorbent. The prepared solid dispersions were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). MATERIALS AND METHODS Materials EZE was kindly gifted by Mepro Pharmaceuticals Ltd. (Surendranagar, India). Gelucire 44/14 was a generous gift sample from Gattefosse Pvt. Ltd. (Mumbai, India). PEG 4000 and PEG 6000 were purchased from Sisco Research Lab Pvt. Ltd. (Mumbai, India). All reagents were of analytical grade. Double-distilled water was used throughout the work. Methods Phase Solubility Phase solubility studies were carried out as described by Higuchi and Connors (10). A quantity of EZE (about 10 mg) that exceeded its solubility was added to flasks containing 25 mL of solutions of different polymer *Corresponding author. diss-18-03-07.indd 55 8/31/2011 3:26:40 PM dx.doi.org/10.14227/DT180311P55

We report a sighting of Cinereous Vulture Aegypius monachus from Mukundara Hills Tiger Reserve in Rajasthan, India. The current observations were made during a two month study on ‘Prey status and abundance in Mukundara Hills Tiger Reserve’ during February-March 2015. Five species of vulture were recorded during this period: Egyptian Vulture Neophron percnopterus ; Long-billed Vulture Gyps indicus ; Griffon Vulture Gyps fulvus ; Red-headed Vulture Sarcogyps calvus and Cinereous Vulture. This is an additional record of a Cinereous Vulture sighting in the area. We highlight the need to evaluate the historical and current status of vulture populations in the area and assess the threats posed to vultures from unorganized carcass dumping sites in and around the reserve, as the past studies have been limited only to the north-western part of the reserve.

The purpose of this research was to study the aqueous-based film coating of tablets utilizing a laboratory-scale side-vented perforated pan-coating apparatus. The process parameters of potential importance with respect to the final film quality were evaluated by using trial and error method. Tablets were evaluated for coating uniformity (mg), coating process efficiency (%), surface roughness, and %LOD (loss on drying). Spray rate and inlet air temperature both affect the all characteristic of coated tablets. Rotating speed of pan mainly affect the coating uniformity of tablets. % Solid content affects the surface of coated tablets and also creates a problem in spray flow. The process parameters relevant to a side-vented perforated pan coating process can be identified and, consequently, optimized.

Lamotrigine (LMN) is an antiepileptic drug, with poor aqueous solubility, which might lead to erratic bioavailability. The objective of the present work was to improve the dissolution characteristics of the LMN using Hydroxy propyl β-cyclodextrin (HP β-CD), which might offer reliable bioavailability. The phase solubility profile was classified as A L -type, revealing 1:1 stoichiometric complexation, with a stability constant (Ks) of 573 M−1. Binary systems of LMN and HP β-CD were prepared in different molar ratios (1:1, 1:2, 1:3 and 1:4) by kneading method. The binary systems were characterized by Fourier Transform Infrared (FT-IR) Spectroscopy, Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction Analysis (PXRD). Results revealed that in the kneaded products the entire drug was entrapped inside the HP β-CD cavity and reduction in drug crystallinity also took place, which may be responsible for improved dissolution characteristics as compared to that of the pure drug as depicted from the dissolution studies.

Pattern formation is investigated in a modified ferroin-catalyzed Belousov−Zhabotinsky (BZ) reaction under the conditions where the stirred system exhibits sequential oscillations. In accord with the temporal dynamics, sequential waves which are separated by a long quiescent time during which the system does not support any wave activity are achieved, providing the first experimental evidence of the connection between revival wave formation and dynamics of sequential oscillations. The initial wave and quiescent window, which last for several hours, are characterized as a function of 1,4-cyclohexanedione, sulfuric acid, and bromate concentrations. In addition to the strong photosensitivity, where both the initial and revival waves can be quickly quenched by illumination, this modified BZ medium also exhibits the potential of producing complex spatiotemporal behavior such as waves with anomalous dispersions.

The present work is aimed to develop and optimize pulsatile delivery during dissolution of an improved formulation of valsartan to coordinate the drug release with circadian rhythm. Preliminary studies suggested that β cyclodextrin could improve the solubility of valsartan and showed AL type solubility curve. A 1:1 stoichiometric ratio of valsartan to β cyclodextrin was revealed from phase solubility studies and Job's plot. The prepared complex showed significantly better dissolution efficiency (p

Etoricoxib is a cyclooxygenase 2 (COX-2) inhibitor that selectively inhibits the COX-2 enzyme and decreases the incidences of side effects associated with these agents. It is commonly prescribed for acute pain, gouty arthritis, and rheumatoid arthritis. Conventional tablets of etoricoxib are not capable of rapid action, which is required for faster drug effect onset and immediate relief from pain. Thus, the aim of the present investigation is to formulate orally disintegrating tablets (ODTs) of etoricoxib. A combination of the superdisintegrants with a sublimation technique was used to prepare the tablets. Tablets were prepared using a direct compression method employing superdisintegrants such as low substituted hydroxylpropyl methyl cellulose (L-HPMC), low substituted hydroxyl-propyl cellulose (L-HPC), crospovidone, croscarmellose sodium, and sodium starch glycolate. Tablets of etoricoxib prepared using L-HPC exhibited the least friability and disintegration time (approximately 65 s). To decrease the disintegration time further, a sublimation technique was used along with the superdisintegrants for the preparation of ODTs. The use of sublimating agents including camphor, menthol, and thymol was explored. The addition of camphor lowered the disintegration time (approximately 30 s) further, but the percent friability was increased. A 3(2) full factorial design was employed to study the joint influence of the amount of superdisintegrant (L-HPC) and the amount of sublimating agent (camphor) on the percent of friability and the disintegration time. The results of multiple linear regression analysis revealed that for obtaining an effective ODT of etoricoxib, higher percentages of L-HPC and camphor should be used. Checkpoint batches were prepared to validate the evolved mathematical model. A response surface plot is also presented to graphically represent the effect of the independent variables on the percent of friability and the disintegration time. The approach using the optimization technique helped to produce a detailed understanding of the effects of formulation parameters.

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