Enhancement of solubility and release profile of simvastatin by co-crystallization with citric acid

Purpose: To enhance the solubility and dissolution profile of simvastatin (SIM) via co-crystallization with varying levels of citric acid using various techniques. Method: Simvastatin-citric acid (SIM-CA) co-crystals were prepared using dry grinding, slurry, liquidassisted grinding, and solvent evaporation techniques, and their various properties were compared. A total of twelve formulations (CC01 to CC12) were prepared. Optimized formulations were selected on the basis of dissolution profiles. Flow properties were evaluated using micromeritic analysis, yielding angle of repose, Carr’s index and Hausner’s ratio. Zeta sizer was employed to evaluate particle size distribution, while surface morphology was determined using scanning electron microscopy (SEM). Melting temperature, stability and physical interaction of simvastatin-citric acid co-crystals were determined by thermal analysis and FTIR. The crystalline nature of the co-crystals was evaluated by powder x-ray diffraction analysis, while solubility and dissolution studies were performed to determine in vitro drug release behavior. Results: Micromeritic analysis revealed good flow properties of SIM-CA co-crystals. Results of Zeta sizer analysis showed that the particle sizes of the co-crystals were in the nanometer range, while SEM revealed that the co-crystals had regular cubical shape. Thermal stability studies with TGA and DSC showed that the co-crystals were stable at temperatures exceeding 400 oC. FTIR results revealed minor shifts in 2956 and 1706 cm-1 peaks. Co-crystal formation was confirmed by PXRD data. The drug release profiles of the optimized formulations (CC02, CC07 and CC11) were 11.36 - 94.46, 12.36 - 95.46 and 13.36 - 96.46 %, respectively. There was significant improvement in solubilities of the optimum formulations, with values of 310.18, 427.21 and 522.02 % for CC02, CC07 and CC11, respectively. Conclusion: Citric acid improves the solubility and dissolution profile of the poorly water-soluble drug, simvastatin, which suggests that co-crystallization can potentially enhance the bioavailability of the drug

Impact of Socio-Demographic Characteristics on the Pattern of Skin Diseases Attending Different Dermatology Department of Public Hospitals Quetta, Pakistan

Abstract Objective: The study was conducted to determine the pattern of skin diseases affecting by the socio-demographic characteristics of the patients visiting the dermatology department of public hospitals in Quetta, Pakistan. Methodology: The prospective cross-sectional study was undertaken using a self prepapred proforma to compile the data while interviewing the patients attending the Dermatology Department of two public hospitals of Quetta, Pakistan, in order to determine the relationship between the demographic characteristics of patients and pattern of skin diseases.    Results: A total of 503 patients were enrolled in the study. Majority of the participants (33.8%) were categorized in the age group of 21-30 years. The most common patterns of skin diseases seen in outpatient department were eczema (21.5%), scabies (19.7%) and bacterial infections (12.7%). Inferential statistics revealed a significant relationship (p=0.001) between pattern of skin diseases and age, education, house occupancy, location and living standards of the study participants. Most of the patients were found to be living in a combined family system (65.6%), with poor living standards (81.7%) and uneducated (51.1%). Conclusion The current study presented that eczema and infectious diseases were the most common pattern of skin diseases in Quetta and they are significantly related  with socio-demographics of the patients so it can be concluded that better health education, maintaining personal hygiene, and improvement in the standard of living may aid a lot in managing and preventing the common skin diseases

Usability Evaluation of E-Commerce Mobile Application

Mobile is not only reducing the distance between the people; it is also providing easiness for people to buy items remotely in just one click. In today’s global village, different companies like Ali Express, eBay, Amazon, Daraz, Olx, Goto, and others have provided electronic commerce (e-commerce) platforms by offering facilities of mobile applications for users. During the current coronavirus (COVID-19) pandemic, the e-commerce landscape is changing rapidly, and on top of health concerns, brands across the globe are concerned about how COVID-19 will impact e-commerce. Most of the people all around the world using these e-commerce applications for grocery, daily usage products, or for clothing. Providing a better User Experience (UX) to the users, the user interface (UI) of e-commerce applications should be simple and easy to use for attracting users. But there are usability issues that developers cannot comprehend because these issues can only be identified with the help of users interacting with the UI. Therefore, to evaluate the usability and to find out the user’s satisfaction System Usability Scale (SUS) is conducted on popular e-commerce mobile applications, including Ali Express, Daraz, and Goto. Sixty-Eight participants evaluated the interface from Pakistan. The results illustrated 71%, 69%, and 55% user satisfaction for Ali Express, Daraz, and Goto, respectively. Moreover, five usability experts evaluated the Goto interface to identify the existing issues in the UI. The results revealed a path for designers to develop an efficient UI interface for e-commerce applications

A new fitness-based selection operator for genetic algorithms to maintain the equilibrium of selection pressure and population

A genetic algorithm is one of the best optimization techniques for solving complex nature optimization problems. Different selection schemes have been proposed in the literature to address the major weaknesses of GA i.e., premature convergence and low computational efficiency. This article proposed a new selection operator that provides a better trade-off between selection pressure and population diversity while considering the relative importance of each individual. The average accuracy of the proposed operator has been measured by χ2 goodness of fit test. It has been performed on two different populations to show its consistency. Also, its performance has been evaluated on fourteen benchmark problems while comparing it with competing selection operators. Results show the effective performance in terms of two statistics i.e., less average and standard deviation values. Further, the performance indexes and the GA convergence show that the proposed operator takes better care of selection pressure and population diversity

Small Mammals of Family Muridae in Protected Areas of Pakistan

Murids to have more than 1300 species globally, forming the largest mammal group. Murids are found nearly everywhere in the world, though many subfamilies have narrower ranges. Murids are not found in Antarctica and many oceanic islands. Five National Parks from Northern areas of Pakistan were physically surveyed. The parks were studied at different times. Dhirkot National Park (DNP) in February 2008, Banjosa National Park (BJNP) from May to June 2009, Pir Lasura National Park (PLNP) from June to July 2009 and Pir Chanasi National Park (PCNP) from April to May 2010. A total of 6 species belonging to the Muridae family were found cumulatively in the study areas

USE OF GLUTARIC ACID TO IMPROVE THE SOLUBILITY AND DISSOLUTION PROFILE OF GLIPIZIDE THROUGH PHARMACEUTICAL COCRYSTALLIZATION

The purpose of current study was to improve the solubility and dissolution profile of BCS class-II drug Glipizide using glutaric acid as a coformer via various cocrystalization techniques i.e., dry grinding, liquid assisted grinding, slurry and solvent evaporation. Fourier Transform Infrared Spectroscopy (FTIR) was performed to determine the interaction between components of glipizide-glutaric acid (GPZ-GLU) cocrystals. Powder X-ray Diffraction (PXRD) studies confirmed the crystalline nature of formulated cocrystals. Scanning Electron Microscopy (SEM) revealed cylindrical to rectangular shape of cocrystals. Flow properties of GPZ-GLU cocrystals were evaluated by micromeritics analysis. Size and surface morphology was determined by zeta sizer analysis and optical microscopy. Differential scanning calorimetry (DSC) and Thermogravimetric (TGA) analysis were performed to determine the melting points as well as thermal stability of pure components and formulated GPZ-GLU cocrystals. In-vitro drug release studies were carried out using dissolution apparatus-II. GPZ-GLU cocrystals showed higher drug release at pH 6.8 as compared to pH 1.2. However, percent drug release of optimum formulations at pH 6.8 was determined as; 24%-92.2% (F3) and 12.0%-93.5% (F7). Solubility studies revealed improved solubility as compared to pure drug in water i.e., 53 folds and 54.27 folds from F3 and F7 cocrystals, respectively. Finally it was concluded that glutaric acid has improved the solubility and dissolution profile of glipizide. However, many cocrystal formers have been reported in literature that can be used to enhance the physicochemical properties as well as bioavailability of poorly soluble drugs via cocrystalization technique

Undiagnosed Hepatitis B and C Virus Infection at a Teaching Hospital in Rawalpindi

Uncontrolled prevalence of hepatitis B and C virus infections is known to be a global health problem. Many cases are undiagnosed yet. So, this study focusses on the undiagnosed existence of viral infection of hepatitis B (HBV) and Hepatitis C infection (HCV) in hospitalized patients and outdoor attendees to draw a more accurate picture of the prevalence of HBV and HCV. A cross-sectional observational study at Benazir Bhutto hospital Rawalpindi Pakistan continued for seven months and included hospitalized patients and outdoor attendees. Venous blood collected from 2003 subjects and processed to investigate infection by ELISA. We observed the overall prevalence of HBV was 2.6% and HCV was 10.98%. Further 4.2% was the highest infection rate of HBV in patients of Surgery and Medicine and the lowest in Orthopedics, Urology, Gynecology and Obstetrics, Pediatrics, Intensive Care Unit, Ear Throat and Nose, Eye>0.001%. We found the highest rate of HCV infection was in Medicine 22.90% and the lowest was in Pediatrics>0.001%. For the age, the HBV infection was found to be 4.55% the most prevalent in the age range of 61-75 and the lowest>0.001% in 76-90 years. Age group 46-60 years showed the highest 19.07% and 16-30 years the lowest 6.44% prevalence of HCV infection. Observed HBV-positive participants were 60.78% males and 39.22% females. While among the participants, males contributed 50.90% H C Virus infections and females contributed 49.10% infections. Although undiagnosed but prevalence of hepatitis B and C virus infection is very high. Therefore, some effective strategies should be implemented

Molecular modeling of novel 2-aminopyridine derivatives as potential JAK2 inhibitors: a rational strategy for promising anticancer agents

Janus kinase 2(JAK2) is a potential target for anticancer drugs in the treatment of numerous myeloproliferative diseases due to its central role in the JAK/STAT signaling cascade. In this study, the binding behavior of 2 amino-pyridine derivatives as JAK2 inhibitors was investigated by using multifaceted strategies including 3D-QSAR, molecular docking, Fingerprint analysis, MD simulations, and MM-PBSA calculations. A credible COMFA (q2 = 0.606 and r2 = 0.919) and COMSIA (q2 = 0.641 and r2 = 0.992) model was developed, where the internal and external validation revealed that the obtained 3D-QSAR models could be capable of predicting bioactivities of JAK2 inhibitors. The structural criteria provided by the contour maps of model were used to computationally develop more potent 100 new JAK2 inhibitors. Docking studies were conducted on the model data set and newly developed compounds (in-house library) to demonstrate their binding mechanism and highlight the key interacting residues within JAK2 active site. The selected docked complexes underwent MD simulation (100 ns), which contributed in the further study of the binding interactions. Binding free energy analyses (MMGB/PBSA) revealed that key residues such as Glu930, Leu932 (hinge region), Asp939 (solvent accessible region), Arg980, Asn981and Asp994 (catalytic site) have a significantly facilitate ligand-protein interactions through H-bonding and van der Waals interactions. The preliminary in-silico ADMET evaluation revealed encouraging results for all the modeled and in-house library compounds. The findings of this research have the potential to offer valuable recommendations for the advancement of novel, potent, and efficacious JAK2 inhibitors. Overall, this work has successfully employed a wide range of computer-based methodologies to understand the interaction dynamics between 2-amino-pyridine derivatives and the JAK2 enzyme, which is a crucial target in myeloproliferative disorders. Communicated by Ramaswamy H. Sarma</p