Design and Develop Bilayered Oral Sustained Matrix Tablets of Pioglitazone Hydrochloride and Metformin Hydrochloride

AIM AND OBJECTIVES: The aim of this investigation is to Design and Develop Bilayered oral sustained matrix tablets of Pioglitazone hydrochloride and Metformin hydrochloride. The concept of Bilayered tablet technology is utilized for stabilization of two incompatible drugs, taste masking of drugs, delivering two drugs having synergistic effects or to deliver a drug for biphasic drug release profile and for the purpose of extension of patents. A Bilayered tablet comprises of two layers among which the first layer is immediate release layer for sudden onset of action and the second layer is Sustained release layer to maintain the steady state concentrations of drug in the blood. Pioglitazone HCl is thiazolidinedione (TZD) class of drug with hypoglycemic, antihyperglycemic and antidiabetic action. Chemically Pioglitazone is (RS)-5-(4-[2-(5- ethylpyridin-2-yl) ethoxy] benzyl) thiazolidine-2, 4-dione. Pioglitazone is used for the treatment of diabetes mellitus type 2 (previously known as non-insulin-dependent diabetes mellitus, NIDDM) in monotherapy and in combination with a sulfonylurea, Metformin. Pioglitazone has also been used to treat non-alcoholic fatty liver. Pioglitazone has also been found to reduce the risk of conversion from prediabetes to diabetes mellitus type 2 by 72%. It has short biological half life of 3-5 hrs (Ramesh et al). Metformin HCl is a biguanide oral anti hyperglycemic (anti diabetic) agent. It is used as an adjunct to diet and exercise for the management of type 2(non-insulindependent diabetes mellitus) diabetes mellitus in patients whose hyperglycemia cannot be controlled by diet alone. As Metformin HCl possess short biological half life (1.5-4.5 hrs), patient should go for frequent administration usually twice or thrice a day which might be a risk to the patient. In order to overcome this Metformin HCl sustained release dosage forms are formulated (Ramesh et al). SUMMARY AND CONCLUSION: In the present investigation, Sustained release Bilayered tablets of Pioglitazone HCl and Metformin HCl were formulated by Direct Compression technique and Wet Granulation technique. Bilayered tablets comprise of IR for sudden onset of action formulated with Crospovidone and SR layer formulated with Polyethylene oxide (PEO- 303) and Carbopol 971 P inorder to sustain the drug release. Drug-excepient compatibility were studied by FT-IR spectral analysis, the results revealed that there were no interactions between drug and excepients in this investigation for the development of the Bilayered tablet formulation. The Precompressional parameters for IR, SR layer formulations ie; Angle of repose, Bulk density, Tapped density, Compressibility index, Hausner’s ratio were studied and found to be in satisfactory limits indicating that the Physical mixtures of the formulations are suitable to formulate the Bilayered tablets. Postcompressional parameters for Bilayered tablets ie; Weight variation, Hardness, Friability, Drug content, were evaluated and the results obtained were satisfactory. The in-vitro drug dissolution studies were carried out for the formulations in pH 1.2 and pH 6.8 phosphate buffer for 2hrs and 10hrs respectively and based on the in-vitro drug release profile IR layer formulation (F3) was optimized for the further development of Bilayered tablets. The formulation F8 comprising of PEO-303 and the formulation F13 comprising of CARBOPOL 971P sustained the drug release for a period of 12 hrs. Dissolution profile of formulations F8 and F13 were compared with the dissolution profile of marketed formulation and Similarity factor for the formulations F8 and F13 was found to be 51.41 and 51.21 respectively.The similarity factor (f2) was also calculated in order to compare optimized formulation (F8 and F13) with that of the reference formulations. Comparission of the profiles indicated that the formulations (F8and F13) had a profile similar to the reference formulation (f2 = 51.41and 51.21) respectively. So these two formulations were comparable with the marketed formulation. The conclusions drawn from the results include: Pioglitazone HCl and Metformin HCL and the excepients selected for this investigation were compatible and it was confirmed by FT-IR studies. Precompressional and Postcompressional parameters were found to be within the satisfactory limits and hence suitable to formulate Bilayered tablets. The order of cumulative % drug release from IR layer formulations was found to be F3>F2>F1. The IR layer formulation ie; F3 was optimized because it released the maximum amount of the drug. The results of in-vitro drug release profile of Bilayered tablets depicts that increase in polymer concentration, increases the retardation of drug release from the SR layer of a Bilayered tablet. The desired drug release rate obtained for F8 and F13 was found to be near to that of the theoretical desired drug release rate. The desired drug release rate obtained for F8 and F13 was found to be near to that of the drug release rate of Marketed formulation. The formulations F8 and F13 were suitable to sustain the drug release for a period of 12hrs, followed first order kinetics exhibited Higuchi’s model and Krosmeyer Peppas exponential coefficient ‘n’ < 0.5 indicates that the release was governed by Fickian diffusion. Hence can conclude that formulated Bilayered tablets of Pioglitazone HCl and Metformin HCl were developed successfully with IR layer comprising of Crospovidone and SR layer comprising of PEO-303 and CARBOPOL 971P as polymers by Direct Compression technique and Wet Granulation technique. From the above results it can be concluded that by using PEO-303 and CARBOPOL 971P we can successfully formulate Bilayer tablets of Pioglitazone HCl and Metformin HCl which showed sustained drug release up to 12hours

Automated assessment of COVID-19 reporting and data system and chest CT severity scores in patients suspected of having COVID-19 using artificial intelligence

Background: The coronavirus disease 2019 (COVID-19) pandemic has spread across the globe with alarming speed, morbidity, and mortality. Immediate triage of patients with chest infections suspected to be caused by COVID-19 using chest CT may be of assistance when results from definitive viral testing are delayed.Purpose: To develop and validate an artificial intelligence (AI) system to score the likelihood and extent of pulmonary COVID-19 on chest CT scans using the COVID-19 Reporting and Data System (CO-RADS) and CT severity scoring systems.Materials and Methods: The CO-RADS AI system consists of three deep-learning algorithms that automatically segment the five pulmonary lobes, assign a CO-RADS score for the suspicion of COVID-19, and assign a CT severity score for the degree of parenchymal involvement per lobe. This study retrospectively included patients who underwent a nonenhanced chest CT examination because of clinical suspicion of COVID-19 at two medical centers. The system was trained, validated, and tested with data from one of the centers. Data from the second center served as an external test set. Diagnostic performance and agreement with scores assigned by eight independent observers were measured using receiver operating characteristic analysis, linearly weighted kappa values, and classification accuracy.Results: A total of 105 patients (mean age, 62 years +/- 16 [standard deviation]; 61 men) and 262 patients (mean age, 64 years +/- 16; 154 men) were evaluated in the internal and external test sets, respectively. The system discriminated between patients with COVID-19 and those without COVID-19, with areas under the receiver operating characteristic curve of 0.95 (95% CI: 0.91, 0.98) and 0.88 (95% CI: 0.84, 0.93), for the internal and external test sets, respectively. Agreement with the eight human observers was moderate to substantial, with mean linearly weighted k values of 0.60 +/- 0.01 for CO-RADS scores and 0.54 +/- 0.01 for CT severity scores.Conclusion: With high diagnostic performance, the CO-RADS AI system correctly identified patients with COVID-19 using chest CT scans and assigned standardized CO-RADS and CT severity scores that demonstrated good agreement with findings from eight independent observers and generalized well to external data. (C) RSNA, 2020Cardiovascular Aspects of Radiolog

Hybrid H-DOC: A bait for analyzing cyber attacker behavior

Cyber security is a vital concern for companies with internet-based cloud networks. These networks are constantly vulnerable to attack, whether from inside or outside organization. Due to the ever-changing nature of the cyber world, security solutions must be updated regularly in order to keep infrastructure secure. With the use of attack detection approaches, security systems such as antivirus, firewalls, or intrusion detection systems have become more effective. However, conventional systems are unable to detect zero-day attacks or behavioral changes. These drawbacks can be overcome by setting up a honeypot. In this paper, a hybrid Honeynet model deployed in Docker (H-DOC) bait has been proposed that comprises both low interaction and high interaction honeypot to attract the malicious attacker and to analyze the behavioral patterns. This is a form of bait, designed to detect or block attacks, or to divert an attacker\u27s attention away from the legitimate services. It focuses only on the SSH protocol, as it is widely used for remote system access and is a popular target of attacks. The proposed Hybrid H-DOC method identify ransomware activity, attack trends, and timely decision-making through the use of an effective rule and tunes the firewall. The attack detection accuracy of the proposed Hybrid H-DOC method when compared with IDH, Decepti-SCADA, AS-IDS and HDCM is 13.97%, 11.82%, 8.60% and 5.07% respectively

Utilization of limestone mineral wastes for developing self-compacting micro concrete

This study aims at investigating the feasibility of replacing cement and fine aggregate by limestone mineral wastes in developing Self Compacting Micro Concrete (SCMC). SCMC is highly flowable and can be used in places where there is no access to vibrators for compaction. Hence, these types of micro concretes are used mainly for repair purposes. The novelty of the work is that fines and coarse form of limestone mineral wastes generated during the beneficiation of a low-grade limestone ore has been studied for its utility as cement and fine aggregate substitute respectively in the preparation of SCMC. The main requirement for repair concrete such as flowability has been studied along with other mechanical properties. Flowability of mixes were assessed by mini slump test and V-funnel test. Mechanical properties namely compressive strength, flexural strength and split tensile strength tests were also studied to evaluate the performance efficacy. It was found that with 100% coarse limestone waste of less than 1mm in size as fine aggregate, it is possible to achieve about 25 MPa and 45 MPa compressive strength at 3 and 28 days respectively. As high flowability and early age strength are of significant parameters for the development of micro concrete, the mix made of 100% limestone wastes as fine aggregate is found to be a successful mix for sustainable development of micro concrete

Physical activity intensity is associated with cognition and functional connectivity in Parkinson's disease.

Cognitive impairment is common in Parkinson's disease (PD) and often leads to dementia, with no effective treatment. Aging studies suggest that physical activity (PA) intensity has a positive impact on cognition and enhanced functional connectivity may underlie these benefits. However, less is known in PD. This cross-sectional study examined the relationship between PA intensity, cognitive performance, and resting state functional connectivity in PD and whether PA intensity influences the relationship between functional connectivity and cognitive performance.96 individuals with mild-moderate PD completed a comprehensive neuropsychological battery. Intensity of PA was objectively captured over a seven-day period using a wearable device (ActiGraph). Time spent in light and moderate intensity PA was determined based on standardized actigraphy cut points. Resting-state fMRI was assessed in a subset of 50 individuals to examine brain-wide functional connectivity.Moderate intensity PA (MIPA), but not light PA, was associated with better global cognition, visuospatial function, memory, and executive function. Individuals who met the WHO recommendation of ≥150&nbsp;min/week of MIPA demonstrated better global cognition, executive function, and visuospatial function. Resting-state functional connectivity associated with MIPA included a combination of brainstem, hippocampus, and regions in the frontal, cingulate, and parietal cortices, which showed higher connectivity across the brain in those achieving the WHO MIPA recommendation. Meeting this recommendation positively moderated the associations between identified functional connectivity and global cognition, visuospatial function, and language.Encouraging MIPA, particularly the WHO recommendation of ≥150&nbsp;min of MIPA/week, may represent an important prescription for PD cognition