This study involves mathematical simulation model such as in vitro-in vivo correlation (IVIVC) development for various extended release formulations of nimesulide loaded hydroxypropylmethylcellulose (HPMC) microparticles (M1, M2 and M3 containing 1, 2, and 3 g HPMC, respectively and 1 g drug in each) having variable release characteristics. In vitro dissolution data of these formulations were correlated to their relevant in vivo absorption profiles followed by predictability worth analysis of these Level A IVIVC. Nimaran was used as control formulation to validate developed formulations and their respective models. The regression coefficients of IVIVC plots for M1, M2, M3 and Nimaran were 0.834 9, 0.831 2, 0.927 2 and 0.898 1, respectively. The internal prediction error for all formulations was within limits, i.e., < 10%. A good IVIVC was found for controlled release nimesulide loaded HPMC floating M3 microparticles. In other words, this mathematical simulation model is best fit for biowaiver studies which involves study parameters as those adopted for M3 because the value of its IVIVC regression coefficient is the closest to 1 as compared to M1 and M2.

Background: Post-occlusive skin reactive hyperaemia (PORH) is a model used to assess microvascular reactivity. This study aims to compare PORH response among pregnant hypercholesterolaemic patients with age and gestational age-matched controls. Methods: This cross sectional study involved 17 hypercholesterolaemic, pregnant women and 20 pregnant controls entering their early third trimester. Laser Doppler fluximetry (LDF) was used to measure skin perfusion. The process of PORH was performed by occluding the upper arm with an occlusion cuff at 200 mmHg for 3 minutes. Skin perfusion was recorded before, during, and after occlusion release. Baseline perfusion, time to achieve peak perfusion (Tp), peak perfusion after occlusion release (PORHpeak), and maximum change in perfusion due to occlusion (PORHmax) were recorded. Results: Serum total cholesterol (TC) was significantly different (P < 0.001) between the 2 groups: 7.25 (SEM 0.18) mmol/L for hypercholesterolaemic women and 5.54 (SEM 0.15) mmol/L for the control group. There were no significant differences in their baseline, PORHpeak, and PORHmax. However, Tp in the hypercholesterolaemic group was significantly increased (P = 0.024) compared with the controls at 14.9 (SEM 0.6) seconds and 13.1 (SEM 0.5) seconds, respectively. Conclusion: Pregnant hypercholesterolaemic patients showed an abnormal microvascular reactivity response. Tp with ischemia was significantly increased compared with normocholesterolaemic controls.

This study involves mathematical simulation model such as in vitro-in vivo correlation (IVIVC) development for various extended release formulations of nimesulide loaded hydroxypropylmethylcellulose (HPMC) microparticles (M1, M2 and M3 containing 1, 2, and 3 g HPMC, respectively and 1 g drug in each) having variable release characteristics. In vitro dissolution data of these formulations were correlated to their relevant in vivo absorption profiles followed by predictability worth analysis of these Level A IVIVC. Nimaran was used as control formulation to validate developed formulations and their respective models. The regression coefficients of IVIVC plots for M1, M2, M3 and Nimaran were 0.834 9, 0.831 2, 0.927 2 and 0.898 1, respectively. The internal prediction error for all formulations was within limits, i.e., < 10%. A good IVIVC was found for controlled release nimesulide loaded HPMC floating M3 microparticles. In other words, this mathematical simulation model is best fit for biowaiver studies which involves study parameters as those adopted for M3 because the value of its IVIVC regression coefficient is the closest to 1 as compared to M1 and M2.
Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; pharmacokinetics ; Cross-Over Studies ; Cyclooxygenase 2 Inhibitors ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; Humans ; Hypromellose Derivatives ; Methylcellulose ; analogs & derivatives ; Microspheres ; Models, Chemical ; Sulfonamides ; administration & dosage ; pharmacokinetics

A multi-centred study was designed to collect dengue epidemiologic data from government and registered private hospitals/clinics and maintained archive of frozen specimens in bio-bank to be used for future dengue epidemic control program, and assess the epidemiology of dengue fever (DF) by evaluating biochemical and oxidative status of patients. ELISA IgM antibodies test was done to confirm DF. From August 2010 to December 2011, 101 confirmed blood samples of DF patients referred to pathology lab of Jinnah Hospital Lahore were subjected to the epidemiologic assessment by evaluating the biochemical and physiological indices and alterations of circulating antioxidants. Clinical features of DF patients and effect of fever on blood components and serum proteins of liver were recorded. The hospital stay in DF, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) showed significant difference. Significant increases in serum alanine amino transferase (ALT) (P=0.000), aspartate amino transferase (AST) (P=0.000), alkaline phosphatase (ALP) (P=0.000), malondialdehyde (MDA) along with significant decreases in total protein (TP) (P=0.000), reduced glutathione (GSH) (P=0.000), superoxide dismutase (SOD), catalase (CAT) (P=0.000), and sialic acid contents (P=0.016) were observed. A positive correlation existed between bound sialic acid levels, liver enzymes and circulating antioxidants (r=0.656, P=0.016). In the present study, alterations of circulating antioxidants in DF suggest that DF might be a metabolic response to an acute, self-limiting tropical viral infection, and a consequence of the viral inflammatory process.
Adult ; Antioxidants ; metabolism ; Biomarkers ; blood ; China ; Dengue ; classification ; diagnosis ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Immunoglobulin M ; metabolism ; Male ; Middle Aged ; Young Adult