Development And Evaluation Of Controlled Release Pellets Of Dil Tiazem Hcl

Satu sistem pelepasan terkawal telah dibangunkan melalui penyalutan satu filem polimer pengawal kadar apa ke atas pelet yang telah disaluti drug, dengan menggunakan diltiazem sebagai drug model. A controlled release system was developed from coating drug layered pellets with a release rate controlling polymer film, using diltiazem as the model drug

Hypertension-related knowledge, medication adherence and health-related quality of life (HRQoL) among hypertensive patients in Islamabad, Pakistan

Purpose: To determine knowledge regarding hypertension, adherence to medication and HealthRelated Quality of Life (HRQoL), and their associations in hypertensive patients in Pakistan. Methods: A cross-sectional study was conducted among 384 hypertensive patients attending a tertiary health care public sector hospital in Islamabad, Pakistan. Data were collected using knowledge questionnaire regarding hypertension, Morisky Medication Adherence Scale, and EuroQol (EQ-5D) scale. Results: The mean systolic and diastolic blood pressures of the 384 patients were 140.39 ± 15.485 and 88.74 ± 10.683 mmHg, respectively. The coefficient of correlation between knowledge regarding hypertension and adherence was 0.638 (p < 0.001), showing a positive association. The correlation coefficient between knowledge and HRQoL was 0.709 (p < 0.001), suggesting a good association. The correlation coefficient between adherence to medication and HRQoL was 0.545 (p < 0.001), which indicated a positive correlation. Conclusion: These results indicate that there are statistically significant associations between hypertension knowledge and HRQoL, hypertension knowledge and medication adherence, and between adherence and HRQoL in the hypertensive patients studied

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

Gabapentin and its salicylaldehyde derivative alleviate allodynia and hypoalgesia in a cisplatin-induced neuropathic pain model

Cisplatin is an effective chemotherapeutic agent indicated in cancer chemotherapy. However, its clinical use is associated with peripheral neuropathy that invariably impairs patient quality of life. Gabapentin (GBP) is an effective analgesic for neuropathic pain conditions but its clinical efficacy in cisplatin-induced neuropathic pain (CINP) is limited, in addition to generating unwanted side-effects. In this study, a gabapentin-salicylaldehyde derivative [gabapentsal (GPS)] was synthesized and evaluated to explore any potential benefit in comparison with GBP in a rat model of CIPN. Administration of cisplatin (3.0 mg/kg/week, i.p.) for five consecutive weeks generated reproducible mechanical-allodynia (decreased paw withdrawal threshold to von Frey filament application; PWT, g) and thermal hypoalgesia (increased nociceptive reaction latency in the hot plate paradigm; s). Treatment with GBP or its derivative on the 37th day of the experimental protocol, dose dependently attenuated cisplatin-induced nocifensive behaviors. Accordingly, doses of GBP (50-100 mg/kg, i.p.) and GPS (25-100 mg/kg, i.p.) suppressed the expression of CINP by normalizing the PWT and hot plate response latency 1 h and 3 h post administration. In the rotarod paradigm, GBP at all doses markedly impaired motor performance, whilst GPS was devoid of motor incoordination except at the highest dose, when a mild impairment occurred. Salicylaldehyde alone had no effect on CINP or rotarod performance and neither was there any synergism when coadministered with GBP. These findings suggest that both GBP and GPS have beneficial effects in the neuropathic pain model though GPS may be potentially more useful in the management of CINP

Novel hydroquinone derivatives alleviate algesia, inflammation and pyrexia in the absence of gastric ulcerogenicity

Purpose: To synthesize and characterize novel hydroquinone compounds that exhibit an aspirin-like pharmacological profile devoid of ulcerogenic side effects.Methods: Two novel hydroquinone derivatives, viz, 2,5-bis(piperidinomethyl)hydroquinone and 2,5- bis(pyrrolidinomet hyl)hydroquinone, were synthesized by refluxing hydroquinone, paraformaldehyde and secondary amines (piperidine or pyrrolidine) in ethanol. The structures were authenticated by infrared (IR) spectroscopy, elemental analysis, mass spectrometry (MS) and 1H and 13C nuclear magnetic resonance (NMR) spectroscopic techniques. The synthesized derivatives were evaluated for antinociceptive, anti-inflammatory and antipyretic activities along with gastric-ulcerogenicity using wellknown testing paradigms. Aspirin served as reference standard.Results: The newly synthesized hydroquinone derivatives, significantly attenuated tonic visceral chemically-induced nociception at 10 mg/kg (p < 0.01, p < 0.001), 20 and 40 mg/kg (p < 0.001), inhibited the temporal-inflammatory reaction at 50 mg/kg (2 - 5 h, p < 0.05, p < 0.001), 100 and 150 mg/kg (1 - 5 h, p < 0.05, p < 0.01, p < 0.001) in addition to alleviating the febrile-response at test doses during 0.5 h (p < 0.05, p < 0.01, p < 0.001), 1 and 1.5 h (p < 0.001) of the study period. The synthesized compounds exhibited improved gastric tolerability profile since they were devoid of aspirin-associated biochemical and ulcerative changes. The in silico studies predicted high binding affinity of the hydroquinone derivatives to the active site of the cyclooxygenase 2 (COX-2) enzyme.Conclusion: The synthesized hydroquinone compounds possess analgesic, antipyretic and antiinflammatory properties with low gastric-ulcerogenic potential. This may be credited to preferential inhibition of the COX-2 enzyme and the beneficial basic rather than acidic chemical nature of the compounds. However, further molecular studies are required to substantiate these findings.Keywords: 2,5-Bis(piperidinomethyl)hydroquinone], 2,5- is(pyrrolidinomethyl)hydroquinone, Antiinflammatory, Antinociceptive, Antipyretic, Gastric-ulcerogenicity, Algesi

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 formulation87

Influence of crug solubility, binders and pellet size in formulating sustained release pellets

The aim of the present study was to investigate the effects of drug solubility, inert pellet size and binders used in drug loading on release behavior from Eudragit NE-30 coated pellets. Aqueous solutions of highly water soluble drugs, diltiazem hydrochloride and chlorpheniramine maleate while hydroalcoholic solutions of poorly soluble drugs, diclofenac sodium and theophylline were applied onto inert pellets to produce drug pellets, which were subsequently coated with aqueous polymer dispersion using bottom spray fluidized-bed coater. Coated pellets were cured at 37 ºC for 24 h prior to dissolution studies. Drug release from coated pellets using different drugs showed different release profiles. The larger size pellets displayed significantly slower release rate compared to smaller size pellets. A faster drug release was achieved with PVP for drug loading in contrast to slower release profile with HPMC. Drug pellets can be differentiated using scanning electron microscope compared to pellets coated with Eudragit NE-30Colegio de Farmacéuticos de la Provincia de Buenos Aire

Sustained release of captopril from matrix tablet using methylcellulose in a new derivative form

The present study was aimed to evaluate the suitability of a newly synthesized polymer methylcellulose glutarate (MCG) for sustained release matrix system using antihypertensive drug captopril. Methylcellulose glutarate was first prepared using methylcellulose and glutaric anhydride with 1:0.5 ratio and confirmed with FTIR, NMR and MALDI. MCG was then employed in various amounts with fixed amount of captopril for the preparation of matrix tablets. Decreasing the amount of MCG had no considerable sustaining effect on in vitro drug release from the matrix system. MCG was also evaluated at different pH values and stirring speed and no appreciable difference in the release profiles was noticed. Moreover, dissolution data of optimum formulation followed zero-order kineticColegio de Farmacéuticos de la Provincia de Buenos Aire

Ethylacetate fraction of Anthocleista vogelii Planch demonstrates antiobesity activities in preclinical models

Purpose: To assess the anti-obesity effect of liquid chromatography mass spectrometry (LCMS) profiled ethylacetate fraction (EF) of Anthocleista vogelii Planch on pancreatic lipase activity in vitro, and on obesity-related hormones in high-fat diet (HFD)-induced obese rats. Methods: Chromatographic analysis of EF to identify bioactive compounds was performed using LCMS electrospray ionization mass spectrometry (ESI-MS) positive mode. Thirty Sprague–Dawley rats were divided into 5 groups (n = 6). Group 1 was fed normal pellet diet, while groups 2 - 5 were fed high-fat diet (HFD) for 14 weeks. The rats were treated for 4 weeks from week 10 with 125 mg/kg of EF (group 3), 250 mg/kg of EF (group 4) or 100 mg/kg of orlistat (group 5). Results: Seven alkaloids were identified in EF, namely, 10-hydroxycamtothecin, moschamindole, camptothecin, moschamine, N6-cis-p-coumaroylserotonin, sinomenine and desacetylcolchicine. The EF of A. vogelii exhibited inhibitory activity against pancreatic lipase with half-maximal inhibitory concentration (IC50) of 8.76 ± 0.110 µg/mL. Rats treated with EF (125 and 250 mg/kg) of A. vogelii showed significantly (p < 0.05) decreased feed intake, body weight, leptin and insulin, when compared to HFD controls. Cortisol, serotonin and noradrenaline were significantly (p < 0.05) increased, but changes in thyroid hormones levels in EF-treated rats were not significant (p > 0.05) when compared to HFD controls. Conclusion: The EF of A. vogelii demonstrate anti-obesity activities by inhibiting pancreatic lipase, elevating serotonin and noradrenaline, and increasing leptin sensitivity, leading consequently to decreased body weight of rats. However, the clinical use of EF of A. vogelii as an antiobesity herbal remedy requires further studies on its mechanisms of action

Causes and incidence of community-acquired serious infections among young children in south Asia (ANISA): an observational cohort study.

BACKGROUND: More than 500 000 neonatal deaths per year result from possible serious bacterial infections (pSBIs), but the causes are largely unknown. We investigated the incidence of community-acquired infections caused by specific organisms among neonates in south Asia. METHODS: From 2011 to 2014, we identified babies through population-based pregnancy surveillance at five sites in Bangladesh, India, and Pakistan. Babies were visited at home by community health workers up to ten times from age 0 to 59 days. Illness meeting the WHO definition of pSBI and randomly selected healthy babies were referred to study physicians. The primary objective was to estimate proportions of specific infectious causes by blood culture and Custom TaqMan Array Cards molecular assay (Thermo Fisher, Bartlesville, OK, USA) of blood and respiratory samples. FINDINGS: 6022 pSBI episodes were identified among 63 114 babies (95·4 per 1000 livebirths). Causes were attributed in 28% of episodes (16% bacterial and 12% viral). Mean incidence of bacterial infections was 13·2 (95% credible interval [CrI] 11·2-15·6) per 1000 livebirths and of viral infections was 10·1 (9·4-11·6) per 1000 livebirths. The leading pathogen was respiratory syncytial virus (5·4, 95% CrI 4·8-6·3 episodes per 1000 livebirths), followed by Ureaplasma spp (2·4, 1·6-3·2 episodes per 1000 livebirths). Among babies who died, causes were attributed to 46% of pSBI episodes, among which 92% were bacterial. 85 (83%) of 102 blood culture isolates were susceptible to penicillin, ampicillin, gentamicin, or a combination of these drugs. INTERPRETATION: Non-attribution of a cause in a high proportion of patients suggests that a substantial proportion of pSBI episodes might not have been due to infection. The predominance of bacterial causes among babies who died, however, indicates that appropriate prevention measures and management could substantially affect neonatal mortality. Susceptibility of bacterial isolates to first-line antibiotics emphasises the need for prudent and limited use of newer-generation antibiotics. Furthermore, the predominance of atypical bacteria we found and high incidence of respiratory syncytial virus indicated that changes in management strategies for treatment and prevention are needed. Given the burden of disease, prevention of respiratory syncytial virus would have a notable effect on the overall health system and achievement of Sustainable Development Goal. FUNDING: Bill & Melinda Gates Foundation