A Review on Quality by Design Approach (QBD) for Pharmaceuticals

Quality by Design is the modern approach for quality of pharmaceuticals. It describes use of Quality by Design to ensure quality of Pharmaceuticals. In this review, the Quality by Design is described and some of its elements identified. Process parameters and quality attributes are identified for each unit operation. Benefits, opportunities and steps involved in Quality by Design of Pharmaceutical products are described. It is based on the ICH Guidelines Q8 for pharmaceutical development, Q9 for quality risk management, Q10 for pharmaceutical quality systems. It also gives application of Quality by Design in pharmaceutical development and manufacturing of pharmaceuticals. It includes the Quality target product profile, critical quality attributes and key aspects of Quality by Design. It also gives comparison between product quality by end product testing and product quality by Quality by Design. The foundation of Quality by Design is ICH Guidelines. Keywords: QbD design, ICH, QTPP, CQA, PAT

Optimized Hydrophobic Interactions and Hydrogen Bonding at the Target-Ligand Interface Leads the Pathways of Drug-Designing

Weak intermolecular interactions such as hydrogen bonding and hydrophobic interactions are key players in stabilizing energetically-favored ligands, in an open conformational environment of protein structures. However, it is still poorly understood how the binding parameters associated with these interactions facilitate a drug-lead to recognize a specific target and improve drugs efficacy. To understand this, comprehensive analysis of hydrophobic interactions, hydrogen bonding and binding affinity have been analyzed at the interface of c-Src and c-Abl kinases and 4-amino substituted 1H-pyrazolo [3, 4-d] pyrimidine compounds.In-silico docking studies were performed, using Discovery Studio software modules LigandFit, CDOCKER and ZDOCK, to investigate the role of ligand binding affinity at the hydrophobic pocket of c-Src and c-Abl kinase. Hydrophobic and hydrogen bonding interactions of docked molecules were compared using LigPlot program. Furthermore, 3D-QSAR and MFA calculations were scrutinized to quantify the role of weak interactions in binding affinity and drug efficacy.The in-silico method has enabled us to reveal that a multi-targeted small molecule binds with low affinity to its respective targets. But its binding affinity can be altered by integrating the conformationally favored functional groups at the active site of the ligand-target interface. Docking studies of 4-amino-substituted molecules at the bioactive cascade of the c-Src and c-Abl have concluded that 3D structural folding at the protein-ligand groove is also a hallmark for molecular recognition of multi-targeted compounds and for predicting their biological activity. The results presented here demonstrate that hydrogen bonding and optimized hydrophobic interactions both stabilize the ligands at the target site, and help alter binding affinity and drug efficacy

Red flags for the early detection of spinal infection in back pain patients

© 2019 The Author(s). Background: Red flags are signs and symptoms that are possible indicators of serious spinal pathology. There is limited evidence or guidance on how red flags should be used in practice. Due to the lack of robust evidence for many red flags their use has been questioned. The aim was to conduct a systematic review specifically reporting on studies that evaluated the diagnostic accuracy of red flags for Spinal Infection in patients with low back pain. Methods: Searches were carried out to identify the literature from inception to March 2019. The databases searched were Medline, CINHAL Plus, Web of Science, Embase, Cochrane, Pedro, OpenGrey and Grey Literature Report. Two reviewers screened article texts, one reviewer extracted data and details of each study, a second reviewer independently checked a random sample of the data extracted. Results: Forty papers met the eligibility criteria. A total of 2224 cases of spinal infection were identified, of which 1385 (62%) were men and 773 (38%) were women mean age of 55 (± 8) years. In total there were 46 items, 23 determinants and 23 clinical features. Spinal pain (72%) and fever (55%) were the most common clinical features, Diabetes (18%) and IV drug use (9%) were the most occurring determinants. MRI was the most used radiological test and Staphylococcus aureus (27%), Mycobacterium tuberculosis (12%) were the most common microorganisms detected in cases. Conclusion: The current evidence surrounding red flags for spinal infection remains small, it was not possible to assess the diagnostic accuracy of red flags for spinal infection, as such, a descriptive review reporting the characteristics of those presenting with spinal infection was carried out. In our review, spinal infection was common in those who had conditions associated with immunosuppression. Additionally, the most frequently reported clinical feature was the classic triad of spinal pain, fever and neurological dysfunction. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Acid base disturbances in uncontrolled type II Diabetes Mellitus.

Aim: To estimate pH, pCO2, pO2 and bicarbonate (HCO3─) levels in arterial blood of diabetes mellitus type II patients. Material and Method: 90 subjects above the age of 40 years were participated in the present study, subdivided in Group 1: 30 diabetic subjects suffering from diabetes mellitus type II as diagnosed by the physician and having random plasma glucose < 400 mg/dl. Group 2: 30 diabetic subjects suffering from diabetes mellitus type II as diagnosed by the physician and having random plasma glucose ≥ 400 mg dl (uncontrolled). Control group: 30 non-diabetic subjects. Arterial blood samples were collected from radial artery in a heparinised syringe. Result: Arterial pH was not significantly decreased (> 0.05) when Group 1 (7.38 ± 0 .09) was compared with control group (7.405 ± 0.044) but significantly decreased (< 0. 05) when Group 2 (7.31 ± 0.11) was compared with control group (7.405 ± 0.044) as well as significantly decreased (< 0.05) when Group 2 (7.31 ± 0.11) was compared with Group 1 (7.38 ± 0.09). Arterial pCO2 was not significantly decreased (>0.05) when Group 1 (36.13 ± 14.20) was compared with control group (39.56 ± 4.50) but significantly decreased (< 0. 05) when Group 2 (31.93 ± 9.50) was compared with control group (39.56 ± 4.50) as well as significantly decreased (< 0.05) when Group 2 (31.93 ± 9.50) was compared with Group 1 (36.13 ± 14.20).  Arterial pO2 was not significantly decreased (>0.05) when Group 1 (88.06 ± 7.09) was compared with) control group (93.16 ± 5.18) but highly significantly decreased (< 0.001) when Group 2 (81.23 ± 12.96) was compared with control group (93.16 ± 5.18)  as well as significantly decreased (< 0.05) when Group 2 (81.23 ± 12.96) was compared with Group 1 (88.06 ± 7.09). Plasma (HCO3─) was not significantly decreased (>0.05) when Group 1 (20.99 ± 6.72) was compared with control group (22.65 ± 1.58) but significantly decreased (< 0.05) when Group 2 (16.95 ± 5.69) was compared with control group (22.65 ± 1.58) as well as significantly decreased (<0.05) when Group 2 (16.95 ± 5.69) was compared with Group 1 (20.99 ± 6.72). Conclusion: Uncontrolled hyperglycemia (group 2 cases) is significantly associated with acid base imbalance in type II diabetes mellitus patients

Ureteric Injury During Transvaginal Oocyte Retrieval (TVOR) and Review of Literature

We report a case of ureteric injury during transvaginal oocyte retrieval (TVOR), which was identified immediately (on the operation table) and managed successfully in the same sitting. A 28-year-old woman with primary infertility underwent in-vitro fertilisation (IVF) in a private centre. Because of the policy of doing an ultrasonography post-procedure, she was diagnosed immediately with vaginal vault haematoma and ureteric injury. A double-J catheter was inserted under cystoscopic guidance. A major complication was averted by the timely diagnosis of ureteric injury and its appropriate management. To conclude, given the elective nature of TVOR and IVF, patients should be informed about all potential complications, including ureteric injury. Early diagnosis of complications (by knowing and anticipating potential risks of procedure) leads to efficient management by timely intervention

Cardiotonic activity of aqueous extract of heartwood of <i style="">Pterocarpus marsupium</i>

532-537The present study was undertaken to evaluate cardiotonic activity of aqueous extract of heartwood of P. marsupium. This plant species contains 5,7,2-4 tetrahydroxy isoflavone 6-6 glucoside which are potent antioxidant and are believed to prevent cardiovascular diseases. Cardiotonic effect of aqueous extract of heartwood of P. marsupium was studied by using isolated frog heart perfusion technique (IFHP). Calcium free Ringer solution was used as vehicle for administration of aqueous extract of P. marsupium as a test extract and digoxin as a standard. A significant increase in height of force of contraction (positive inotropic effect) and decrease in heart rate (negative chronotropic effect) at a very low concentration (0.25 mg/ml) was observed with test extract as compared to the same dose of a standard digoxin. The present results indicated that a significant increase in height of force of contraction with decrease in heart rate was observed as the dose of test extract increased. The test extract produced cardiac arrest at 4 mg/ml, a higher concentration, as compared to standard, digoxin (0.5 mg/ml). Compared to digoxin, a drug with narrow therapeutic window, P. marsupium showed wide therapeutic window

Undergroundcablefaultdistancelocator

This paper proposes fault location model for underground power cable using microcontroller. The aim of this project is to determine the distance of underground cable fault from base station in kilometers. This project uses the simple concept of ohm's law.When any fault like short circuit occurs, voltage drop will vary depending on the length of fault in cable,since the current varies. A set of resistors are therefore used to represent the cable and a dc voltage is fed at one end and the fault is detected by detecting the change in voltage using a analog to voltage converter and a microcontroller is used to make the necessary calculations so that the fault distance is displayed on the LCD display