Enhanced Oral Bioavailability of Epalrestat SBE7-ß-CD Complex Loaded Chitosan Nanoparticles: Preparation, Characterization and in-vivo Pharmacokinetic Evaluation.

BACKGROUND: Epalrestat (EPL) is a carboxylic acid derivative with poor aqueous solubility and its pharmacokinetic features are not fully defined. PURPOSE: Current research aimed to fabricate inclusion complexation of EPL with SBE7 ß-CD (IC) and EPL/SBE7 ß-CD CS NPs (NP). METHODS: EPL was complexed with SBE7 ß-CD using the co-precipitation method, and the prepared complex was fabricated into nanoparticles using the ionic gelation method. The prepared formulations were characterized for particle size analysis, surface morphology, and in vitro dissolution study. The % inhibition of EPL against α-glucosidase enzyme was also conducted to check the drug's antidiabetic activity. Finally, an in vivo pharmacokinetic investigation was carried out to determine the concentration of EPL in rabbit plasma of the prepared formulation. In vivo pharmacokinetic studies were conducted by giving a single dose of pure EPL, IC, and NP. RESULTS: The size of NP was found to be 241.5 nm with PDI 0.363 and zeta potential of +31.8 mV. The surface of the prepared NP was non-porous, smooth and spherical when compared with pure EPL, SBE7 ß-CD and IC. The cumulative drug release (%) from IC and NP was 73% and 88%, respectively, as compared to pure drug (25%). The % inhibition results for in vitro α-glucosidase was reported to be 74.1% and the predicted binding energy for in silico molecular docking was calculated to be -6.6 kcal/mol. The calculated Cmax values for EPL, IC and NP were 4.75±3.64, 66.91±7.58 and 84.27±6.91 µg/mL, respectively. The elimination half-life of EPL was 4 h and reduced to 2 h for IC and NP. The AUC0-α for EPL, IC and NP were 191.5±164.63, 1054.23±161.77 and 1072.5±159.54 µg/mL*h, respectively. CONCLUSION: Taking these parameters into consideration it can be concluded that IC and NP have prospective applications for greatly improved delivery and regulatedt release of poorly water soluble drugs, potentially leading to increase therapeutic efficacy and fewer side effects.

Quantification of Bioactive Compounds and Evaluation of the Antioxidant Activity of Carissa edulis Valh (Apocynaceae) Leaves.

Carissa edulis is a plant used in the management of oxidative stress and inflammatory related disorders such as malaria, rheumatism inflammation, and cardiovascular diseases. The present study evaluates the total phenolic content, antioxidant capacity (DPPH, ABTS, and FRAP), and the bioactive compounds present in the various extracts of C. edulis (HEC, MEC, AEC, and PC). An HPLC analysis determined the different compounds present in the extracts. High concentration of total phenolic content was observed in aqueous and methanolic extracts more than in the hydroethanolic extract though not significantly different. Flavonoids were higher in the hydroethanolic and methanolic extracts, respectively, with 14.84 mg RE/g extract and 12.02 mg RE/g extract. Tannins were also found in large amounts in the same two extracts with 26.76 mg TAE/g extract and 34.67 mg TEE/g extract. The percentage radical scavenging activity DPPH ranged between 58.63% and 94.67% for aqueous extract and for ABTS between 51.39% and 94.12% for the methanolic extract. The highest FRAP was obtained in the methanolic extract (6.73 g AAE/100 g extract). HPLC analysis revealed the presence of quercetin, rutin, and gallic acid in the different extracts. C. edulis represents a potential source of bioactive components with antioxidant capacity.

sessment Of Blood Pressure and Health-Related Quality of Life Among Hypertensive Patients: An Observational Study.

OBJECTIVES: Objective • Health-related quality of life (HRQoL) is an important tool in the assessment of treatment outcomes. Healthcare professionals use the concept of HRQoL to measure factors other than illness which affect human health and its status. Patient's everyday activities are adversely affected by hypertension (HTN) and results in decreased self-confidence. The present study was aimed to assess blood pressure and health-related quality of life (HRQoL) of hypertensive patients in Pakistan. METHODS: A questionnaire-based cross-sectional study was undertaken with 384 hypertensive patients attending a tertiary care public sector hospital in Islamabad, Pakistan. The assessment of HRQoL was done by using an EuroQol EQ-5D scale. Values derived from the UK general population survey were used to score HRQoL. The blood pressure of each patient was measured by using a calibrated sphygmomanometer. Data analysis was performed by using SPSS version 21 (SPSS Inc., Chicago, IL, USA). P ≤ .05 was taken as significant. RESULTS: Two hundred and fifteen (56%) patients were male with 3.31 ± 2.13 years of history of hypertension. The majority (n = 138, 35.9%) was categorized in the age group of 41 to 50 years with mean age of 50.21 ± 9.51. Mean (SD) systolic BP and mean (SD) diastolic BP was measured as 140.39 ± 15.485 and 88.74 ± 10.683 in mmHg respectively. Poor HRQoL was measured among the study participants (0.6456 ± 0.2317). Age, gender, education, occupation and monthly income had a significant relation with HRQoL score. CONCLUSION: Hypertension imposes an adverse effect on patient's HRQoL. Results from this study could be useful in clinical practice. Attention is required to highlight determinants of HRQoL and policies should be implemented for better management of HTN, particularly in early treatment phases where it is still possible to improve HRQoL.

Antihyperlipidemic studies of newly synthesized phenolic derivatives: in silico and in vivo approaches.

BACKGROUND: Hyperlipidemia is a worth-mentioning risk factor in quickly expanding cardiovascular diseases, including myocardial infarction and, furthermore, in stroke. METHODS: The present work describes the synthesis of phenolic derivatives 4a-e and 6a-c with the aim of developing antihyperlipidemic agents. The structures of the synthesized compounds were confirmed by spectroscopic data. The in silico docking studies were performed against human 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase enzyme (PDB ID: 1HWK), and it was observed that compounds 4a and 6a exhibited maximum binding affinity with target protein having binding energies -8.3 and -7.9 kcal, respectively. RESULTS: Compound 4a interacts with amino acids Val805 with distance 1.89 Å and Met656, Thr558, and Glu559 with bonding distances 2.96, 2.70, and 2.20 Å, respectively. The in vivo antihyperlipidemic activity results revealed that compound 4a indicated minimum weight increment, ie, 20% compared with 35% weight increment with standard drug atorvastatin during 6 weeks of treatment. Moreover, increment in high-density lipoprotein cholesterol and decrease in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were more prominent in case of 4a compared to atorvastatin with P<0.05. The synthesized compounds were nontoxic and well tolerated because none of the mice were found to suffer from any kind of morbidity and death during 6 weeks of dosing. CONCLUSION: Based on our pharmacological evaluation, we may propose that compound 4a may act as a lead structure for the design and development of more potent antihyperlipidemic drugs.

Antidiabetic Activities of an LC/MS Fingerprinted Aqueous Extract of Fagonia cretica L. in Preclinical Models.

Diabetes mellitus is a chronic disease and one of the most important public health challenges facing mankind. Fagonia cretica is a medicinal plant used widely in the Punjab in Pakistan. A recent survey has demonstrated that traditional healers and herbalists frequently use this plant to treat diabetes. In the current study, the traditional medicine was prepared as a tea, and the profile of the main metabolites present in the traditional medicine was analysed via LC/MS/MS. The extract was shown to contain a number of phenolic glycosides including quercetin-3-O-rutinoside, kaempferol-3-O-rutinoside, kaempferol-3-O-glycoside, kaempferol-3(6'-malonylglucoside), isorhamnetin-3-O-rutinoside, and isorhamnetin 3-(6″-malonylglucoside) in addition to two unidentified sulphonated saponins. The traditional medicine inhibits α-glucosidase in vitro with an IC50 of 4.62 µg/mL. The hypoglycaemic effect of the traditional medicine was evaluated in normoglycaemic and streptozotocin-treated diabetic rats, using glibenclamide as an internal control. The preparation (250 or 500 mg/kg body weight) was administered once a day for 21 consecutive days. The dose of 500 mg/kg was effective in the management of the disease, causing a 45 % decrease in the plasma glucose level at the end of the experimental period. Histological analysis of pancreatic sections confirmed that streptozotocin/nictotinamide treatment caused destruction of pancreatic islet cells, while pancreatic sections from the treatment groups showed that both the extract and glibenclamide partially prevented this deterioration. The mechanism of this protective effect is unclear. However, such a finding suggests that ingestion of the tea could confer additional benefits and should be investigated further.

Physicochemical, in vitro and in vivo evaluation of flurbiprofen microemulsion.

Flurbiprofen, a potent nonsteroidal anti-inflammatory drug, is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrheal. However, this drug has many gastrointestinal side effects produced by its oral administration, such as gastric bleeding and peptic ulcer. These effects were responsible for non-compliance among patients, which ultimately results in treatment failure. The physicochemical properties of flurbiprofen, make it a suitable candidate for transdermal drug delivery, which can overcome the drawbacks of oral administration. In this sense, microemulsions have been proved to increase the cutaneous absorption of lipophilic drugs when compared to conventional drug delivery systems. The purpose of this study was to formulate and characterize gel based microemulsions, for topical delivery of flurbiprofen. Different gel bases, containing microemulsion and hydro-alcoholic solution of flurbiprofen, were developed and compared. In vitro study showed that gels containing microemulsion had a higher permeation rate than those containing hydro-alcoholic solutions. Additionally, formulation of Carbopol-I (microemulsion) showed higher percent of inhibition of inflammation than others bases. Further, skin irritation study demonstrated that Carbopol-I was none irritating. Flurbiprofen microemulsion incorporated on Carbopol-I showed physicochemical, in vitro and in vivo characteristics suitable for the development of alternative transdermal delivery formulation.

Comparative bioavailability and in vitro in vivo correlation of two sustained release brands of theophylline: tablets and pellets.

To investigate the influence of dosage forms on bioavailability, a randomized single-dose crossover study under fasting conditions was conducted using two commercially available sustained release products, Quibron SR tablets and Respro-SR pellets filled Capsules containing 300mg theophylline. A group of 12 healthy, male human subjects participated in this study. Serial blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h. Theophylline was measured by high-performance liquid chromatography while absorption profiles were derived using Wagner-Nelson equation. The bioavailability of Quibron SR tablets was compared with Respro-SR pellets filled Capsules 300 mg using pharmacokinetic parameters Cmax, Tmax, AUC(0-t), and AUC(0-alpha). In addition, the 90% confidence interval (CI) for the ratio of logarithmic transformed C(max) and AUC(0-alpha) was also used to determine bioequivalence. The T/R (test/reference) ratio of Quibron SR tablets was quite close to the prescribed limits of bioequivalence i.e. 80-125%. No statistically difference was observed between the log transformed AUC(0-agr;) (P=0.971) values as well as log transformed C(max) values (P=0.854) indicating bio-availability and the extent of absorption of two brands were comparable. Moreover, the value of correlation coefficients for % in vivo absorption versus % in vitro dissolution of the two products was calculated to be 0.9533 for Respro-SR capsule and 0.9789 for Quibron-SR tablets.