Acetaminophen is a widely used oral analgesic and antipyretic medication; however, quality control parameters may differ across various brands. The aim of the present study was to evaluate and compare critical quality attributes, including in-vitro dissolution characteristics, of five acetaminophen tablet brands (labeled A-E) from the Saudi market and determine their pharmaceutical equivalence. All brands were tested for conformity with the United States Pharmacopoeia (USP) standards, through evaluation of weight variation, hardness, friability, disintegration, and dissolution. Dissolution profiles were compared using model-dependent and independent approaches relative to the innovator brand A (Panadol). All tested brands passed the weight variation and friability tests with deviations of less than 5% from the average weight and less than 1% weight loss, respectively, with the exception of brand C showing relatively higher friability (1.13%). All brands displayed variable disintegration times; however, all were compliant with USP specifications. All studied tablets released less than 80% of the drug within 30 minutes; however, brands B and C had lower drug release rates, area under the curve (AUC), and dissolution efficiency (DE) compared with the innovator. Brand E, on the other hand, had a higher drug release rate, AUC, DE, and mean dissolution time (MDT), and thus was pharmaceutically inequivalent to the innovator. All tested brands exhibited a non swellable matrix diffusioncontrolled dissolution as assessed by the Korsmeyer-Peppas model of drug-release kinetics. In conclusion, all acetaminophen brands were able to pass USP specifications to justify interchangeability. Minor variations in in-vitro dissolution characteristics could reflect inherent manufacturing compounding differences.

New Findings What is the central question of this study?Is aortic dysfunction, a significant contributor to cardiovascular disease in metabolic syndrome, expressed uniformly across both the thoracic and abdominal aorta? What is the main finding and its importance?Our study shows that, in the setting of metabolic syndrome, functional and structural deficits in the aorta are differentially expressed along its length, with the abdominal portion displaying more extensive vascular abnormalities. It is, therefore, likely that early interventional strategies targeting the abdominal aorta might alleviate cardiovascular pathologies driven by the metabolic syndrome. Abstract The extent of vascular dysfunction associated with metabolic syndrome might vary along the length of the aorta. In this study, we investigated regional functional and structural changes in the thoracic and abdominal aorta of a rat model of metabolic syndrome, namely, high‐fat diet (HFD) streptozotocin‐induced diabetes mellitus (HFD‐D). Four‐week‐old male Wistar albino rats were fed with either HFD or control diet (CD) for 10 weeks. At week 6, 40 mg/kg streptozotocin and its vehicle were injected i.p. into HFD and CD groups, respectively. At the end of the feeding period, rats were euthanised and aortic segments collected for assessment of vascular functional responses and histomorphometry. Tail‐cuff systolic blood pressures (154 ± 6  vs. 110 ± 4 mmHg) and areas under the curve for oral glucose and i.p. insulin tolerance tests were greater in HFD‐D versus CD rats. Abdominal aortic vasoconstriction in response to noradrenaline and KCl was greater in HFD‐D compared with CD rats. Thoracic vasoconstrictor responses to noradrenaline, but not KCl, were greater in the HFD‐D group. Abdominal, but not thoracic, endothelium‐dependent vasorelaxation in response to acetylcholine was blunted in HFD‐D relative to CD rats; however, nitric oxide‐dependent vasorelaxation in HFD‐D rats was impaired in both thoracic and abdominal segments. The abdominal aorta of HFD‐D rats showed deranged interlamellar spacing and increased lipid plaque deposition. In conclusion, vascular dysfunction in metabolic syndrome is expressed differentially along the length of the aorta, with the abdominal aorta exhibiting increased susceptibility to vasoconstrictors and greater deficits in endothelium‐dependent relaxation. These vascular functional abnormalities could potentially underlie the development of hypertensive cardiovascular disease associated with the metabolic syndrome.

Objective: Metabolic syndrome, driven by obesity and diabetes, is a major contributor to cardiovascular disease. While large arteries vascular dysfunction is a well-documented phenomenon of metabolic syndrome, vascular disease of smaller diameter arteries, which are key contributors to peripheral vascular resistance and blood pressure control, remains uncertain. Using in-vitro organ-bath preparation, this study, therefore, investigated functional responses of the superior mesenteric and right iliac arteries in a high fat diet (HFD)/streptozotocin-induced diabetes mellitus rat model. Design and method: Five-week-old male Wistar Albino rats (n = 24) were fed with either HFD (45 kcal% fat) or control diet (10 kcal% fat) for 10 weeks. At 10 weeks of age, 40 mg/kg streptozotocin and saline were injected intraperitoneally into the HFD and control groups, respectively. Results: Diabetic HFD rats displayed a time-dependent increase (p < 0.01) in water intake, urine output, fasting blood glucose and tailcuff systolic blood pressure compared to controls (154 ± 6 vs. 110 ± 4 mmHg). Both mesenteric and iliac vasoconstrictor responses (N/g) to norepinephrine (1E-9 – 3E-5 M), but not to the depolarizing signals of high potassium (5 – 120 mM), were greater (p < 0.01) in the HFD group relative to controls. Mesenteric, but not iliac, endothelium-dependent vasorelaxation to acetylcholine (1E-10 – 1E-5 M) was blunted (p < 0.05) in the HFD rats compared with controls. In contrast, mesenteric and iliac endothelium-independent vasorelaxation responses to sodium nitroprusside (1E-11 – 1E-6 M) remained comparable between groups. Conclusions: Vascular functional responses in smaller diameter arteries are differentially expressed in metabolic syndrome, demonstrating upregulated vasoconstriction to adrenergic stimuli and/or impaired endothelium-dependent relaxation. These vascular abnormalities align with those previously described in larger arteries and could therefore further promote the development of cardiovascular disease in metabolic syndrome.

Objective: Obesity and diabetes constitute a hallmark of metabolic syndrome that is directly linked to vascular dysfunction and high blood pressure (BP). Accordingly, we aimed to investigate regional functional changes in thoracic and abdominal aortic responses in a rat model of high fat diet (HFD) and streptozotocin (STZ)-induced diabetes mellitus. Design and method: Five weeks old male Wistar Albino rats (n = 24) were fed with either HFD (45 kcal% fat) or control diet (10 kcal% fat) for 10 weeks. At 10 weeks of age, 40 mg/kg STZ and saline were injected intraperitoneally into the HFD and control groups, respectively. At the end of the treatment, rats were euthanized to assess vasoconstrictor and vasodilator responses of dissected aortic segments. Results: Conscious tail-cuff systolic BP was higher in the HFD relative to control (154 ± 6 mmHg vs. 110 ± 4 mmHg, p < 0.001). Oral glucose tolerance test (oGTT) generated greater AUCs in the HFD rats relative to controls (64,361 ± 383 vs. 14,169 ± 398, p < 0.001). Abdominal aortic vasoconstriction (N/g) to norepinephrine (NE, 1E-9 – 3E-5 M) and the depolarizing signals of high potassium (KCl, 5 – 120 mM) was greater (p < 0.05) in the HFD group compared with controls. Thoracic aortic vasoconstrictor responses (N/g) to NE, but not KCl, were greater (p < 0.05) in the HFD group as compared to controls. Abdominal, but not thoracic, endothelium-dependent vasorelaxation to acetylcholine (1E-10 – 1E-5 M) was blunted (p < 0.05) in the HFD group relative to controls. In contrast, thoracic and abdominal aortic responses to sodium nitroprusside (SNP)-induced endothelium-independent relaxation remained comparable between groups. Conclusions: Vascular functional responses are altered along the descending aorta in metabolic syndrome, exhibiting exaggerated vasocontractility and impaired endothelium-dependent relaxation. These vascular functional abnormalities could potentially underlie the development of hypertensive cardiovascular disease associated with the metabolic syndrome.

The aim of this study was to predict the blood/plasma drug concentration profiles for five brand of nifedipine present on the Saudi Arabia market by using the numerical convolution method and to estimate the pharmacokinetic parameters (Cmax, Tmax, Ka, K and Vd) by the application of the residual method to the predicted plasma drug concentration profiles. Results showed that the higher Cmax was 118.95ng/ml for brand A2 and the lower Cmax was 72.29ng/ml for brand A3. The Tmax was ranged from 2.3 hr to 4.9 hr for brands A2 and A3 respectively. The total area under plasma drug concentration curve (AUCinf.) was in lower value equal to 585.59 ng x hr/ml for brand A2 and the higher value was for brand A5 equal to 743.52ng x hr/ml. The volume of distribution was also increased from 52.5 L for free nifidipine to 72 L for brand A1. The predicted first order elimination rate constant was decreased from 0.34 hr-1 for free nifedipine to 0.17 hr-1 for brand A3. The half-life of nifedapine was increased from 2 hours for free drug to 3.93 hours for brand A3. From this study it can be concluded that brands present in the market that shows similarity in accordance to the Dissimilarity factor f1 are not always guaranty that they will be bioequivalent in vivo and vice versa. Also, this study indicates that the method of convolution is a useful tool for prediction of bioequivalence of different brands present on the market.