DEVELOPMENT OF SUSTAINED RELEASE ALOGLIPTIN TABLETS USING A MULTIPARTICULATES SYSTEM MADE OF BENTONITE

Objective: This study was designed to evaluate the use of bentonite in the formulation of sustained-release tablets containing alogliptin benzoate after granulation. Methods: Bentonite was used for preparing tablets after granulation. The prepared tablets were tested for their pharmacopeial requirements. Further, a high-performance liquid chromatography (HPLC) method was developed to assess the release pattern of alogliptin from the tablets. Besides, differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (XRD) were used for evaluating the compatibility the drugs and bentonite. Finally, the release from the tablets was tested using the paddle apparatus. Results: The FTIR and DSC did not show any interaction between the drug and the excipient in contrast to the powder-XRD pattern, which showed a shift for montmorillonite crystal peak. This shift was interpreted by increasing in the spacing of the crystalline structure of montmorillonite. However, the results of pharmacopeial tests showed that the prepared tablets comply with the compendial requirements, In addition, the release profiles of these tablets with aid of hydroxypropyl methylcellulose (HPMC) as a binder revealed a sustained release of alogliptin. Furthermore, the fitting of release data showed that the release from these tablets followed Fickian diffusion that alogliptin released by diffusion from bentonite gel matrix. Conclusion: Bentonite was successfully used for producing sustained-release tablets of alogliptin. However, maintaining the crystal structure of montmorillonite was essential for building the gel structure of bentonite and releasing the drug in a controlled manner

The relationship between dyslipidemia and lupus nephritis in systemic lupus erythematosus patients attending a Saudi Rheumatic Center, Tabuk

Background: There is an increasing awareness of the role of dyslipidemia in lupus nephritis patients, no researchers have studied dyslipidemia in systemic lupus erythematosus (SLE) in Tabuk. In this study, we aimed to investigate the association between dyslipidemia and lupus nephritis in Tabuk, Saudi Arabia. Methods: This cross-sectional comparative longitudinal hospital-based study was conducted at a rheumatic clinic in the North West Armed Force Hospital (NWAFH) during the period April 2014–June 2015. Seventy-three patients diagnosed with SLE were invited to participate in the study. All participants were required to sign a written informed consent, following which they were interviewed using a structured questionnaire. Data collected include demographic data, clinical characteristics, fasting lipid profile, renal function tests, urine analysis, antinuclear antibody, anti-double-stranded antibodies, complement levels, serum albumin, anticardiolipin, ant bodies, and antiphospholipid antibodies. Lupus nephritis was ascertained by renal biopsy. The research was approved by the ethical committees of both the University of Tabuk and the NWAFH and data were analyzed using the Statistical Package for Social Sciences (SPSS). Results: Out of 73 patients with SLE, 86.3% were females with a mean age of  34 ± 6.4 years. Lupus nephritis was evident in 26% of the patients, proteinuria in 44.1%, high total cholesterol in 17.8%, high low-density lipoprotein in 15.1%, high triglycerides in 27.3%, and low high-density lipoproteins in 52.1%. Patients with lupus nephritis had high total cholesterol, high LDL, high TG, and low HDL than those without lupus nephritis P-value < 0.05. Conclusion: Dyslipidemia was more common among patients with SLE nephritis, and an aggressive treatment is recommended to reduce this serious complication. The relatively small size of the study group and the fact that the study was conducted at a single tertiary center are the limitations of this study. Keywords: dyslipidemia, lupus nephritis, Saudi Arabi

Investigation of transdermal permeation of atorvastatinloaded microemulsions

Purpose: To develop microemulsions containing atorvastatin for transdermal application, which will improve the bioavailability and reduce the side effects associated with the oral administration of atorvastatin.Methods: Atorvastatin-loaded microemulsions (MEs) were developed using tween 80 as a nonionic surfactant, isopropyl myristate, polyethylene glycol 400 and dimethyl sulfoxide. Their droplets’ size, and rheological properties were estimated, with the diffusion through the rat’s skin being evaluated using Franz diffusion cells. Furthermore, the in vivo transdermal and oral bioavailability, as well as the toxicity of formulation, were assessed in rats.Results: The results showed that the MEs have a droplet size lower than 100 nm and low Newtonian viscosity. In addition, a flux rate of atorvastatin as high as 10.078 μg/cm2.h was achieved after the loading of the MEs. The in vivo transdermal application maintained a steady state concentration of 1.02μg/mL for 48 h, in comparison to a maximum concentration of 7.7 μg/mL after 2.74 h following oral administration at the same dosing level. Moreover, the transdermally treated rats did not elicit skin irritation.Conclusion: The developed atorvastatin MEs for transdermal application delivers the drug to achieve a controlled plasma level, as well as reduce dosing frequency and toxicity in rats when compared to oral administration. Therefore, the formulation has a potential for development for use in humans

PdO and PtO doped WS2 boosts NO2 gas sensing characteristics at room temperature

In this work tungsten disulphide nanostructures loaded with platinum-oxide (PtO), or palladium-oxide (PdO) were grown directly onto alumina substrates. This was achieved using a combination of aerosol-assisted chemical vapour deposition (AA-CVD) method with atmospheric pressure CVD technique. At first, tungsten oxide nanowires loaded with either PtO or PdO nanoparticles were successfully co-deposited via AA-CVD followed by sulfurization at 900 °C in the next step. The morphological, structural, and chemical characteristics were investigated using FESEM, TEM, XRD, XPS and Raman spectroscopy. The results confirm the presence of PdO and PtO in the WS2 host matrix. Gas sensing attributes of loaded and pristine WS2 sensors were investigated, at room temperature, towards different analytes (NO2, NH3, H2 etc.). Both pristine and metal-oxide loaded WS2 gas sensors show remarkable responses at room temperature towards NO2 detection. Further, the loaded sensors demonstrated stable, reproducible, ultrasensitive, and enhanced gas sensing response, with a detection limit below 25 ppb. Additionally, the effect of ambient humidity on the sensing response of both loaded and pristine sensors was investigated for NO2 gas. The response of PtO loaded sensor considerably decreased in humid environments, while the response for pristine and PdO loaded sensors increased. However, slightly heating (at 100 °C) the sensors, suppresses the influence of humidity. Finally, the long-term stability of different sensors is investigated, and the results demonstrate high stability with repeatable results after 6 weeks of gas sensing tests. This work exploits an attractive pathway to add functionality in the transition metal dichalcogenide host matrix

TRANSDERMAL OF ATENOLOL VIA MICROEMULSIONS

Objective: Developing novel non-ionic microemulsions (MEs) for transdermal of atenolol as satisfactory alternative drug delivery systems for the oral route. Methods: Seven MEs were developed then checked for encapsulation of atenolol using Fourier Transform Infrared Spectroscopy (FTIR-spectroscopy) (), isotropy, droplet sizes, rheological properties and transdermal flux using Franz diffusion cell. Furthermore, two MEs with best flux values were selected for bioavailability evaluation after transdermal application over rat’s skin. Results: The results showed that the MEs complies with colloidal systems properties. Also, the developed MEs were stable throughout the study, ideal viscous systems with droplet sizes below 500 nm and isotropic. Besides, FTIR-spectra could reveal the structure of the MEs and encapsulation of atenolol inside the dispersed phase. Moreover, the flux values of atenolol in MEs through rat’s skin varied with different factors such as atenolol concentration, MEs’s composition, and zetapotential. The highest flux value of the developed systems was 243.5±16.3 µg. cm-2. h-1. Furthermore, the in vivo results showed that using the two tested microemulsions maximum plasma levels of atenolol 5.22±0.43 and 4.06±0.15 mg. ml-1at 8.18 and 3.64 h respectively could be achieved. Conclusion: The developed microemulsions can be promise formulations for transdermal administration of atenolol as alternative for oral tablets

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone