An epidemiological study of psychiatric disorders in Kashmir.

Introduction: Mental disorders are highly prevalent and affect people across all regions of the world. The State of Jammu and Kashmir has been witness to a conflict for about three decades. Little is known about the extent of mental disorders in Kashmir. There was a dire need to estimate the prevalence of mental disorders among the rural population of Kashmir. The study was undertaken to estimate the point prevalence of specific mental disorders in rural population of Kashmir, sociodemographic correlates of mental disorders and to assess the service utilization in individuals with mental disorders. Materials and Methods: Community-based survey carried out in rural districts of Kashmir using a mixed sampling technique. The survey was conducted in six blocks of two districts (Pulwama and Baramulla) of Kashmir. Mini-International Neuropsychiatric Interview (MINI) for psychiatric morbidity was used. Appropriate statistical methods were applied. Results: In total, 11.3% of adult population suffers from mental illness in the valley. As compared to males (8.4%), females had a higher prevalence (12.9%). Depressive disorders (8.4%) were the most common psychiatric disorders, followed by anxiety disorders (5.1%). Only 12.6% of patients suffering from mental disorders had sought treatment for their illnesses. Conclusion: The findings of this study have cleared many doubts and indicated the prevalence of 10 common mental health disorders in the general population as well as among different socioeconomic groups in Kashmir. This study has indicated low levels of treatment sought by people with mental illness.

Development and Validation of Matrix of Chemistry, Manufacturing, and Control (MoCMC) System for Intramammary Drug Products (IMM).

PURPOSE: Products formulated for intramammary (IMM) infusion are intended for the delivery of therapeutic moieties directly into the udder through the teat canal to maximize drug exposure at the targeted clinical site, the mammary gland, with little to no systemic drug exposure. Currently, to our knowledge, there has been no in-vitro matrix system available to differentiate between IMM formulations. Our goal is to develop A custom tailored in-vitro "Matrix of Chemistry, Manufacturing and Control" (MoCMC) System to be a promising future tool for identifying inequivalent IMM formulations. MoCMC can detect inter and intra batch variabilities, thereby identifying potential generics versus brand product similarities or differences with a single numeric value and a specific & distinctive fingerprint. METHODS: The FDA-approved IMM formulation, SPECTRAMASTⓇ LC, was selected as the reference product for the MoCMC. Twelve in-house test formulations containing ceftiofur hydrochloride were formulated and characterized. The MoCMC was developed to include six input parameters and three output parameters. The MoCMC system was used to evaluate and compare SPECTRAMASTⓇ LC with its in-house formulations. RESULTS: Based on the MoCMC generated parameters, the distinctive fingerprints of MoCMC for each IMM formulations, and the statistical analyses of MCI and PPI values, in-house formulations, F-01 and F-02 showed consistency while the rest of in-house formulations (F-03-F-12) were significantly different as compared to SPECTRAMASTⓇ LC. CONCLUSION: This research showed that the MoCMC approach can be used as a tool for intra batch variabilities, generics versus brand products comparisons, post-approval formulations changes, manufacturing changes, and formulation variabilities.

Association of Coagulopathy and Inflammatory Biomarkers with Severity in SARS-CoV-2-Infected Individuals of the Al-Qunfudhah Region of Saudi Arabia.

BACKGROUND: Identifying prognosticators/predictors of COVID-19 severity is the principal focus for early prediction and effective management of the disease in a time-bound and cost-effective manner. We aimed to evaluate COVID-19 severity-dependent alteration in inflammatory and coagulopathy biomarkers. METHODS: A hospital-dependent retrospective observational study (total: n = 377; male, n = 213; and female, n = 164 participants) was undertaken. COVID-19 exposure was assessed by performing real-time PCR on nasopharyngeal (NP) swabs. Descriptive and inferential statistics were applied for both continuous and categorical variables using Rstudio-version-4.0.2. Pearson correlation and regression were executed with a cut-off of p < 0.05 for evaluating significance. Data representation by R-packages and ggplot2. RESULTS: A significant variation in the mean ± SD (highly-sever (HS)/moderately severe (MS)) of CRP (HS/MS: 102.4 ± 22.9/21.3 ± 6.9, p-value < 0.001), D-dimer (HS/MS: 661.1 ± 80.6/348.7 ± 42.9, p-value < 0.001), and ferritin (HS/MS: 875.8 ± 126.8/593.4 ± 67.3, p-value < 0.001) were observed. Thrombocytopenia, high PT, and PTT exhibited an association with the HS individuals (p < 0.001). CRP was correlated with neutrophil (r = 0.77), ferritin (r = 0.74), and WBC (r = 0.8). D-dimer correlated with platelets (r = -0.82), PT (r = 0.22), and PTT (r = 0.37). The adjusted odds ratios (Ad-OR) of CRP, ferritin, D-dimer, platelet, PT, and PTT for HS compared to MS were 1.30 (95% CI -1.137, 1.50; p < 0.001), 1.048 (95% CI -1.03, 1.066; p < 0.001), 1.3 (95% CI -1.24, 1.49, p > 0.05), -0.813 (95% CI -0.734, 0.899, p < 0.001), 1.347 (95% CI -1.15, 1.57, p < 0.001), and 1.234 (95% CI -1.16, 1.314, p < 0.001), respectively. CONCLUSION: SARS-CoV-2 caused alterations in vital laboratory parameters and raised ferritin, CRP, and D-dimer presented an association with disease severity at a significant level.

Comparisons of lumbosacral kinematics among non-specific chronic low back pain subgroups and healthy during prolonged sitting: A cross-sectional observational study.

BACKGROUND: The literature has suggested a variety of postural changes of the spine that possibly contribute to the increase in back pain during sitting in persons with non-specific chronic low back pain (NS-CLBP). However, the heterogeneity of NS-CLBP persons has made the ability to attribute pain increase to a particular sitting posture very difficult. Therefore, the purpose of this study was to compare lumbosacral kinematics and their roles in pain increase among homogenous NS-CLBP subgroups and healthy controls over a 1-h sitting period. METHODS: Twenty NS-CLBP subjects with motor control impairment [10 classified as having flexion pattern (FP) disorder, and 10 with active extension pattern (AEP) disorder], and 10 healthy controls participated in the study. Subjects underwent a 1-h sitting protocol on a standard office chair. Lumbosacral postures including sacral tilt, third lumbar vertebrae (L3) position, and relative lower lumbar angle were recorded using two-dimensional inclinometers over the 1-h period. Perceived back-pain intensity was measured using a visual analog scale every 10 min throughout the sitting period. RESULTS: All study groups (FP, AEP and healthy controls) significantly differed from each other in the measured lumbosacral kinematics at the beginning as well as at the end of the sitting period (p ≤ 0.05). Only the NS-CLBP subgroups showed significant changes in the lumbosacral kinematics across the 1-h sitting period (p < 0.01), and that the directions of change occurred toward end spinal postures (lumbar kyphosis for FP subgroup and lumbar lordosis for the AEP subgroup). In addition, both NS-CLBP subgroups reported a similarly significant increase in pain through mid-sitting (p < 0.001). However, after mid-sitting, the AEP subgroup reported much less increase in pain level that was accompanied by a significant decrease in the lumbar lordotic postures (p = 0.001) compared to FP subgroup. CONCLUSION: The present study's findings suggest that each NS-CLBP subgroup presented with differently inherent sitting postures. These inherently dysfunctional postures coupled with the directional changes in the lumbosacral kinematics toward the extreme ranges across the 1-h sitting period, might explain the significant increase in pain among subgroups.

Bioavailability assessment of a brompheniramine taste-masked pediatric formulation in a juvenile porcine model.

A brompheniramine taste-masked pediatric formulation was developed as part of the National Institutes of Health Pediatric Formulation Initiative to help address low patient compliance caused by the bitter taste of many adult formulations. To confirm that the taste-masked formulation can provide a similar pharmacological effect to the previous marketed adult formulations, a juvenile porcine model was used to screen the model pediatric formulation to compare the bioavailability between the marketed brompheniramine maleate and the taste-masked maleate/tannate formulation. Pigs were dosed orally with both formulations and blood samples were obtained from 0 to 48 h. Plasma samples were prepared and extracted using solid-phase extraction. The mass spectrometer was operated under selected ion monitoring mode. The selected ion monitoring channels were set to m/z 319.1 for brompheniramine and m/z 275.2 for the internal standard chlorpheniramine. Calibration curves were linear over the analytical range 0.2-20 ng/ml (r2 > 0.995) for brompheniramine in plasma. The intra- and inter-day accuracies were between 98.0 and 105% with 5.73% RSD precision. The bioanalytical method was successfully applied to a preclinical bioavailability study. The bioavailability profiles were not significantly different between the two formulations, which demonstrates that taste-masking with tannic acid is a promising approach for formulation modification for pediatric patients.

Perceptions of telemedicine among healthcare professionals in rural tertiary care hospitals of rural Sindh, Pakistan: a qualitative study.

Background: Telemedicine has proven to be a boon in the field of medical sciences, as it provides a platform for all health-care personnel to assist patients remotely through digital technology advancements. It brings hope to the lower middle-income regions of the world. Thus, the study was conducted to explore the perceptions regarding telemedicine among healthcare professionals (HCP) in rural Sindh, Pakistan. Methodology: Overall, 19 in-depth interviews were conducted and this comprised of HCP working in the Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences (PAQSJIMS) and Peoples University of Medical and Health Sciences for Women (PUMHSW) being involved in providing online consultations and practicing telemedicine. The interviews were conducted and audio recorded in Sindhi and Urdu and were later transcribed in to English, coded for themes and sub-themes, and were analyzed using content analysis. Results: The opportunities perceived with the use of telemedicine services were reducing nosocomial infections, facilitating the healthcare in remote areas, handling telemedicine tools, application of telemedicine services on the ground and reducing stress. However, inadequate awareness regarding telemedicine, difficulty in physical examination, the need for training, lack of compliance, and concerns regarding accuracy in diagnosis and treatment were identified as the perceived barriers to the use of telemedicine services. Conclusion: HCP had perception toward telemedicine as have numerous opportunities favoring implementation as well as various barriers are needed to overcome to promote the usage of telemedicine. Increased awareness, training programs, and technological advancements are key to overcome these challenges.

Application and reduction of a nonlinear hyperelastic wall model capturing ex vivo relationships between fluid pressure, area, and wall thickness in normal and hypertensive murine left pulmonary arteries.

Pulmonary hypertension is a cardiovascular disorder manifested by elevated mean arterial blood pressure (>20 mmHg) together with vessel wall stiffening and thickening due to alterations in collagen, elastin, and smooth muscle cells. Hypoxia-induced (type 3) pulmonary hypertension can be studied in animals exposed to a low oxygen environment for prolonged time periods leading to biomechanical alterations in vessel wall structure. This study introduces a novel approach to formulating a reduced order nonlinear elastic structural wall model for a large pulmonary artery. The model relating blood pressure and area is calibrated using ex vivo measurements of vessel diameter and wall thickness changes, under controlled pressure conditions, in left pulmonary arteries isolated from control and hypertensive mice. A two-layer, hyperelastic, and anisotropic model incorporating residual stresses is formulated using the Holzapfel-Gasser-Ogden model. Complex relations predicting vessel area and wall thickness with increasing blood pressure are derived and calibrated using the data. Sensitivity analysis, parameter estimation, subset selection, and physical plausibility arguments are used to systematically reduce the 16-parameter model to one in which a much smaller subset of identifiable parameters is estimated via solution of an inverse problem. Our final reduced one layer model includes a single set of three elastic moduli. Estimated ranges of these parameters demonstrate that nonlinear stiffening is dominated by elastin in the control animals and by collagen in the hypertensive animals. The pressure-area relation developed in this novel manner has potential impact on one-dimensional fluids network models of vessel wall remodeling in the presence of cardiovascular disease.

Local Identifiability Analysis, Parameter Subset Selection and Verification for a Minimal Brain PBPK Model.

Physiologically-based pharmacokinetic (PBPK) modeling is important for studying drug delivery in the central nervous system, including determining antibody exposure, predicting chemical concentrations at target locations, and ensuring accurate dosages. The complexity of PBPK models, involving many variables and parameters, requires a consideration of parameter identifiability; i.e., which parameters can be uniquely determined from data for a specified set of concentrations. We introduce the use of a local sensitivity-based parameter subset selection algorithm in the context of a minimal PBPK (mPBPK) model of the brain for antibody therapeutics. This algorithm is augmented by verification techniques, based on response distributions and energy statistics, to provide a systematic and robust technique to determine identifiable parameter subsets in a PBPK model across a specified time domain of interest. The accuracy of our approach is evaluated for three key concentrations in the mPBPK model for plasma, brain interstitial fluid and brain cerebrospinal fluid. The determination of accurate identifiable parameter subsets is important for model reduction and uncertainty quantification for PBPK models.

Patient In-Use Stability Testing of FDA-Approved Metformin Combination Products for N-Nitrosamine Impurity.

Between February 2020 and January 2022, the Food and Drug Administration (FDA) recalled 281 metformin extended-release products due to the presence of N-nitrosodimethylamine (NDMA) above the acceptable daily intake (ADI, 96 ng/day). Our previous studies indicated presence of NDMA levels above ADI in both metformin immediate and extended-release products. When metformin products have NDMA impurities, it is indispensable to check for the same impurities in metformin combination products. Therefore, the objective of the present study was to evaluate in-use stability of commercial metformin combination products for NDMA. For this purpose, metformin products in combination with glyburide (GB1-GB12), glipizide (GP1-GP8), pioglitazone (P1-P3), alogliptin (A1, A2), and linagliptin (L1, L2) were repacked in pharmacy vials, stored at 30°C/75% RH for 3 months, and monitored for NDMA impurity. The NDMA level varied from 0 to 156.8 ± 32.8 ng/tablet initially and increased to 25.4 ± 5.1 to 455.0 ± 28.4 ng/tablet after 3 months of exposure to in-use condition. Initially, 18 products have NDMA level below ADI limit before exposure which decreased to 7 products (GB5, GP3, GP5, A1, A2, L1, and L2) meeting specification. In conclusion, in-use stability study provides quality and safety risk assessment of drug products where nitroso impurities are detected in the probable condition of use.

In Vitro and In Vivo testing of 3D-Printed Amorphous Lopinavir Printlets by Selective Laser Sinitering: Improved Bioavailability of a Poorly Soluble Drug.

The aim of this paper was to investigate the effects of formulation parameters on the physicochemical and pharmacokinetic (PK) behavior of amorphous printlets of lopinavir (LPV) manufactured by selective laser sintering 3D printing method (SLS). The formulation variables investigated were disintegrants (magnesium aluminum silicate at 5-10%, microcrystalline cellulose at 10-20%) and the polymer (Kollicoat® IR at 42-57%), while keeping printing parameters constant. Differential scanning calorimetry, X-ray powder diffraction, and Fourier-transform infrared analysis confirmed the transformation of the crystalline drug into an amorphous form. A direct correlation was found between the disintegrant concentration and dissolution. The dissolved drug ranged from 71.1 ± 5.7% to 99.3 ± 2.7% within 120 min. A comparative PK study in rabbits showed significant differences in the rate and extent of absorption between printlets and compressed tablets. The values for Tmax, Cmax, and AUC were 4 times faster, and 2.5 and 1.7 times higher in the printlets compared to the compressed tablets, respectively. In conclusion, the SLS printing method can be used to create an amorphous delivery system through a single continuous process.

Development and Validation of Discriminatory In-vitro Release Method for Intramammary Drug Product.

PURPOSE: Intramammary (IMM) formulations are locally acting and delivered intracisternally into the udder. No pharmacopeial in-vitro release method is available to differentiate between the IMM formulations. Our research aim is to develop in-vitro release methods that discriminate different IMM formulations (SPECTRAMAST® LC and in-house formulations). METHODOLOGY: Different in-house formulations were developed to simulate SPECTRAMAST® LC generics. SPECTRAMAST® LC and the in-house formulations were characterized for physicochemical attributes, such as particle size, rheology, drug content, sedimentation rate, and flocculation rate. The in-vitro release method was optimized by evaluating drug release using USP apparatuses 1, 2 (with and without enhancer/customized cells), and 4. Various test parameters, including medium effect (whole homogenized bovine milk versus aqueous buffer), medium volume (200-900 mL), and rotational speed (50-200 rpm) were investigated. RESULTS: Two potential in-vitro systems can be used as discriminatory methods for IMM formulations: USP apparatus 2 with the IMM formulation loaded into two containers a) customized formulation container (83.1 cm in height and 56.4 cm in width) or b) enhancer cells with their top adapted with mesh #40 (rotation speed:125 rpm and 900 mL of whole homogenized bovine milk). The release profile of SPECTRAMAST® LC at 1 h (99.8%) was not significantly different from formulations with similar physicochemical characteristics F-01 (99.1%) and F-02 (100.5%). Formulation with different physicochemical characteristics F-03 (44.3%) and F-04 (57.2%) showed slower release (1 h) than SPECTRAMAST® LC (98.8%). CONCLUSION: The developed in-vitro release methods can be used as a potential tool for in-vitro comparability evaluations for IMM formulations.

Surgical outcomes and stoma-related complications in inflammatory bowel disease in Saudi Arabia: a retrospective study.

BACKGROUND: The prevalence of inflammatory bowel diseases (IBD), Crohn's (C) and ulcerative colitis (UC) has increased in Saudi Arabia during the past decade. Even though medical treatment is first-line therapy, most patients require surgery during the course of the disease. Stoma creation complications in IBD are underreported in the literature of the Middle East and especially in Saudi Arabia. OBJECTIVES: Report the postoperative, stoma and peristomal complications following stoma creation in (C) versus UC. DESIGN: Retrospective cohort study. SETTINGS: Tertiary care center. PATIENTS AND METHODS: Patients with IBD who underwent stoma creation for either UC or CD between August 2015 and July 2020 were included. The diseases were compared to assess their characteristics and association to postoperative, stoma and peristomal complications. All complications were reported over a 90-day duration from the surgery. Patients younger than 14 years of age were excluded. MAIN OUTCOME MEASURES: Postoperative complications, stoma and peristomal complications in IBD patients who underwent stoma creation. SAMPLE SIZE: 50. RESULTS: Of 50 IBD patients underwent stoma creation, 32 patients (64%) were diagnosed with CD and 18 patients (36%) with UC. Most of the procedures in both groups were laparoscopic and elective. Low BMI and serum albumin were more prevalent in the CD group. Postoperative complications were higher in the CD patients compared to the UC patients (CD 40.6% vs UC 11.1%, P=.028) with the most common complication being abdominal collection[a]. Stoma complications were comparable between the two groups (UC 16.7% vs CD 15.6%). However, peristomal complications were higher clinically in UC patients in comparison with the CD patients (UC 61.1% vs CD 37.5% P=.095) with the most common complication being skin excoriation (UC 44.4% vs CD 37.5%). CONCLUSIONS: CD has significantly higher postoperative complications compared to UC. Peristomal complications were high in both groups and had a negative impact on quality of life. Therefore, comprehensive stoma education and regular outpatient follow ups are recommended to improve the overall outcomes. LIMITATIONS: Retrospective and conducted in one academic institution with a small sample size.

Sports-Related Injuries in Adolescent Athletes: A Systematic Review.

Sports participation among adolescents is increasing, offering numerous health benefits and exposing them to the risk of sports-related injuries. This paper aims to understand that the prevalence and risk factors associated with these injuries are crucial for effective injury prevention and the overall well-being of adolescent athletes. This systematic review synthesizes the existing literature on sports-related injuries in adolescent athletes. A comprehensive search was conducted, yielding 11 relevant studies. The studies were analyzed to determine the prevalence of injuries and identify associated risk factors. A qualitative synthesis of the findings was performed. The included studies collectively highlight the significant burden of sports-related injuries among adolescent athletes, with prevalence rates ranging from 34.1% to 65%. Specific risk factors associated with these injuries include body mass index (BMI), physical activity patterns, age, gender, sport type, previous injuries, and training practices. Obese adolescents, those engaged in excessive weekly practice hours, younger athletes, and females were found to be at higher risk. Certain sports, such as soccer and football, exhibited higher injury rates. Sports-related injuries in adolescent athletes are a multifaceted issue influenced by various factors. Tailored injury prevention strategies are essential, considering the specific needs of adolescent athletes in different sports and age groups. Interventions should encompass physical and educational components, emphasizing proper warm-ups, protective equipment use, and injury prevention education. Longitudinal studies and standardized injury reporting systems are needed to monitor injury trends and evaluate prevention strategies effectively. This systematic review contributes to our understanding of sports-related injuries in adolescent athletes and underscores the importance of evidence-based injury prevention efforts.

Preparation and Characterization of 3D-Printed Dose-Flexible Printlets of Tenofovir Disoproxil Fumarate.

The aim of this work was to design pediatric-friendly, dose-flexible orally disintegrating drug delivery systems (printlets) of the antiviral drug tenofovir disoproxil fumarate (TDF) by selective laser sintering (SLS) for potential use in hospitals along with other antiviral drugs. In order to obtain a consistent quality of printlets with desired properties, it is important to understand certain critical quality attributes for their main and interactions effect. The printlets were optimized by Box-Behnken's design of the experiment by varying process variables while keeping the composition constant. The composition contained 16.3% TDF, 72.7% polyvinyl pyrrolidone K16-18, 8% magnesium aluminum silicate, 3% Candurin® NXT Ruby Red, and 0.3% colloidal silicon dioxide. The process variables studied were surface (X1), chamber temperatures (X2), and laser scanning speed (X3). The range of variable levels was 75-85°C for X1, 50-70°C for X2, and 200-240 mm/s for X3, respectively. The responses studied were hardness, disintegration time, dissolution, physiochemical, and pharmacokinetic characterization. X-ray powder diffraction indicated partial or complete conversion of the crystalline drug into amorphous form in the printlets. Comparative pharmacokinetics between Viread® (generic) and printlets in rats were superimposable. Pharmacokinetic parameters showed statistically insignificant differences between the two formulations in terms of Tmax, Cmax, and AUC of (p > 0.05). Printlets were bioequivalent to Viread® as per FDA bioequivalence criteria. Thus, the SLS printing method showed the fabrication of dose-flexible printlets with quality, and in vivo performance equivalent to commercial tablets.

Effect of Melatonin Implants and Nutritional Restriction on Growth Performance of Local Male Lambs.

This experiment was conducted from 17 October 2021 to 9 January 2022 on the Department of Animal Production sheep field at the College of Agriculture, University of Anbar. The study aimed to determine the impact of melatonin implants and dietary restrictions on local male lambs' nutritional and growth performance. It included 16 local male lambs ranging in age from 5 to 6 months and weighing an average of 35.31 3.71 kg. The lambs were separated into four equal groups (n=4) and placed in separate pens. The actual duration of the experiment was 69 days, divided into two phases: the first phase consisted of 42 days of nutritional restriction, and the second phase consisted of 27 days of re-nutrition. As a control treatment during the stage of nutritional restriction, the first group (T1) was fed ad libitum. In contrast, the second group (T2) was fed Ad libitum with 36 mg subcutaneous-ear implanted melatonin implants, and the third group (T3) was fed a restricted diet (R) of 75% of the Ad libitum. Comparatively, the fourth group (T4) was fed a restricted diet of 75% of the Ad libitum with 36 mg of subcutaneous-ear implanted Melatonin. Until the end of the re-feeding phase, all experimental treatments were provided with unrestricted access to food. The nutritional and growth performance parameters were measured during the nutritional restriction and re-feeding stage and the entire experiment duration. During the nutritional restriction stage (42 days), there was no significant difference between the experimental treatments in terms of total weight gain, daily weight gain, feed conversion efficiency, and feeding efficiency. However, the experimental groups exhibited statistically significant differences in daily feed intake, daily dry matter intake, and dry matter intake as a percentage of body weight. In the re-feeding stage, there were no significant differences in the above nutritional and growth parameters among the experimental groups (27 days). This experiment concluded that feeding local male lambs 75% of Ad libitum with or without melatonin implants for 42 days, followed by re-feeding for 27 days, maintained the growth performance of the lambs with minimal feed intake and reduced lamb production costs.

Application of Sucrose Acetate Isobutyrate in Development of Co-Amorphous Formulations of Tacrolimus for Bioavailability Enhancement.

The focus of the present work was to develop co-amorphous dispersion (CAD) formulations of tacrolimus (TAC) using sucrose acetate isobutyrate as a carrier, evaluate by in vitro and in vivo methods and compare its performance with hydroxypropyl methylcellulose (HPMC) based amorphous solid dispersion (ASD) formulation. CAD and ASD formulations were prepared by solvent evaporation method followed by characterization by Fourier transformed infrared spectroscopy, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), dissolution, stability, and pharmacokinetics. XRPD and DSC indicated amorphous phase transformation of the drug in the CAD and ASD formulations, and dissolved more than 85% of the drug in 90 min. No drug crystallization was observed in the thermogram and diffractogram of the formulations after storage at 25 °C/60% RH and 40 °C/75% RH. No significant change in the dissolution profile was observed after and before storage. SAIB-based CAD and HPMC-based ASD formulations were bioequivalent as they met 90% confidence of 90-11.1% for Cmax and AUC. The CAD and ASD formulations exhibited Cmax and AUC 1.7-1.8 and 1.5-1.8 folds of tablet formulations containing the drug's crystalline phase. In conclusion, the stability, dissolution, and pharmacokinetic performance of SAIB-based CAD and HPMC-based ASD formulations were similar, and thus clinical performance would be similar.

In Vitro and In Vivo Characterization of the Transdermal Gel Formulation of Desloratadine for Prevention of Obesity and Metabolic Syndrome.

Chronic use of antihistamines can induce abnormalities in lipid absorption with potential excessive accumulation of lipids in the mesentery that can lead to the development of obesity and a metabolic syndrome. The focus of the present work was to develop a transdermal gel formulation of desloratadine (DES) to prevent/reduce obesity and metabolic syndromes. Nine formulations were prepared to contain hydroxypropyl methylcellulose (2-3%), DES (2.5-5.0%), and Transcutol® (15-20%). The formulations were evaluated for cohesive and adhesive properties, viscosity, drug diffusion through synthetic and pig ear skin, and pharmacokinetics in New Zealand white rabbits. Drug permeation was faster through the skin compared to synthetic membranes. The drug had good permeation, as indicated by very short lag time (0.08-0.47 h) and high flux (59.3-230.7 µg/cm2.h). The maximum plasma concentration (Cmax) and area under the curve (AUC) of transdermal gel formulations were 2.4 and 3.2 fold that of the Clarinex tablet formulation. In conclusion, as indicated by the higher bioavailability, transdermal gel formulation of DES may decrease the dose of the drug, compared to commercial formulation. It has the potential to reduce or eliminate metabolic syndromes associated with oral antihistamine therapy.

Nitroso Impurities in Drug Products: An Overview of Risk Assessment, Regulatory Milieu, and Control Strategy.

Many nitrosamines have been recognized to be carcinogenic for many decades. Despite the fact that several nitrosamine precursors are frequently used in the manufacturing of pharmaceutical products, their potential presence in pharmaceutical products has previously been overlooked due to a lack of understanding on how they form during the manufacturing process. From the risk assessment, it is clear that nitrosamines or their precursors may be present in any component of the finished dosage form. As a risk mitigation strategy, components with a high potential to form nitrosamine should be avoided. In the absence of suitable alternatives, sufficient measures to maintain nitrosamines below acceptable intake levels must be applied. Excipient manufacturing pathways must be extensively studied in order to identify probable excipient components that may contribute to nitrosamine formation. The manufacturers must not solely rely on pharmacopeial specifications for APIs and excipients, rather, they should also develop and implement additional strategies to control nitrosamine impurities. The formulation can be supplemented with nitrosating inhibitors, such as vitamin C, to stop the generation of nitrosamine. The purpose of this review is to identify key risk factors with regard to nitrosamine formation in pharmaceutical dosage forms and provide an effective control strategy to contain them below acceptable daily intake limits.

Pyrimethamine 3D printlets for pediatric toxoplasmosis: design, pharmacokinetics, and anti-toxoplasma activity.

OBJECTIVES: The focus of the present research is to develop printlet formulations of pyrimethamine (PMT). METHODS: Printlets formulation of PMT were developed by screening design by varying laser scanning speed, Kollidon® VA 64, polyvinylpyrrolidone, and disintegrant. RESULTS: Laser scanning speed, Kollidon® VA, and disintegrant had statistically significant effect on hardness, disintegration time, and/or dissolution (p < 0.05). Dissolution was almost 100% in 30 min. X-ray powder diffraction indicated partial amorphous transformation of the crystalline drug. Pharmacokinetic and anti-toxoplasma activity profiles of the printlets and compressed tablets were superimposable with no statistical difference (p > 0.05). CONCLUSION: Clinical performance of the printlets would be similar to the compressed tablets.

Data integrity issues in pharmaceutical industry: Common observations, challenges and mitigations strategies.

Data integrity (DI) reaffirms the pharmaceutical industry's commitment to manufacture drugs that are safe, effective and fulfil quality standards. At the same time, DI is a crucial tool for regulatory authorities to use in protecting public health. Recent FDA Form-483 observations and warning letters indicate that DI is the main issue the pharmaceutical industry is currently dealing with. Failure to comply with DI requirements may result in a high number of un-validated results, which may cause post-marketing issues and frequent product recalls. To address the underlying causes of DI problems, a comprehensive approach is necessary. The majority of DI issues are caused by poor quality culture, organizational or individual behaviour, leadership, processes, or technology. DI should be effectively integrated into the quality management system, and it should apply to both paper and electronic records. Employees should be trained on 21 CFR Part 11. Consistent review and audit are required to ensure that procedures are followed and audit trails are generated. Electronic systems, in addition to being an efficient solution (system integration, data verification at both input and output, security), offer advantages over traditional paper-based systems in terms of improved compliance with DI regulatory requirements. For example, many electronic system platforms provide enhanced security features and audit trail capabilities. Finally, management support for data governance is essential for successful implementation of DI. This article reviews commonly observed deviations by FDA pertaining to DI and discusses measures to be undertaken to avoid them.