Improving Drug Loading of Mucosal Solvent Cast Films Using a Combination of Hydrophilic Polymers With Amoxicillin and Paracetamol as Model Drugs.

Improving drug loading of mucosal solvent cast films using a combination of hydrophilic polymers with amoxicillin and paracetamol as model drugs.

Biomed Res Int. 2013; 2013: 198137
Boateng J, Mani J, Kianfar F

Solvent cast mucosal films with improved drug loading have been developed by combining carboxymethyl cellulose (CMC), sodium alginate (SA), and carrageenan (CAR) using paracetamol and amoxicillin as model drugs and glycerol (GLY) as plasticizer. Films were characterized using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), folding resilience, swelling capacity, mucoadhesivity, and drug dissolution studies. SA, CMC, and GLY (5?:?3?:?6) films showed maximum amoxicillin loading of 26.3% whilst CAR, CMC, and GLY (1?:?2?:?3) films had a maximum paracetamol loading of 40%. XRPD analysis showed different physical forms of the drugs depending on the amount loaded. Films containing 29.4% paracetamol and 26.3% amoxicillin showed molecular dispersion of the drugs while excess paracetamol was observed on the film surface when the maximum 40% was loaded. Work of adhesion was similar for blank films with slightly higher cohesiveness for CAR and CMC based films, but the differences were significant between paracetamol and amoxicillin containing films. The stickiness and cohesiveness for drug loaded films were generally similar with no significant differences. The maximum percentage cumulative drug release was 84.65% and 70.59% for paracetamol and amoxicillin, respectively, with anomalous case two transport mechanism involving both drug diffusion and polymer erosion. HubMed – drug

Effectiveness of aspirin on double lumen permanent catheter efficacy in ESRD.

Nephrourol Mon. 2013; 5(2): 762-5
Mozafar M, Samsami M, Sobhiyeh MR, Jabbehdari S, Fallah Zavareh M

The complications of vascular access are the most imperative etiology for hospitalization, morbidity and mortality in chronic hemodialysis. The most prevalent complication of central catheter is dysfunction due to thrombosis. Aspirin is an anti-aggregative platelet drug that may increase the patency of permanent catheters (perm-cath).The aim of this study was to evaluate the role of Aspirin in perm-cath survival.This study included a total of 185 ESRD cases according to the inclusion criteria for perm-cath insertion in hemodialysis. One hundred and eighty patients following perm-cath insertion had proper blood flow through perm-cath during hemodialysis. Patients were randomly divided between intervention (80 mg/day Aspirin initiated a day following catheter insertion) and control (placebo) groups. The average time that the perm-cath was functional was noted. Demographic characteristics included comorbidities and past history were also used to address probable influence on perm-cath function and patency.The mean survival time of the catheter in Aspirin group was significantly higher than the control group (5.3 ± 4.7 month versus 3.9 ± 2.7 month, P = 0.012). No significant difference in major complications of Aspirin use (such as GI bleeding) was noted between two groups (P = 0.52). In terms of the patient’s demographic characteristics, those of the female gender and a history of diabetes mellitus were found to have significant influence on median survival rate of the catheters (P = 0.021, 0.043 respectively).These results suggest that Aspirin use following perm-cath insertion might be beneficial for catheter survival. This increased survival time might enable patient’s use of AVF maturation for long term dialysis access. HubMed – drug

Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer.

Am J Cancer Res. 2013; 3(3): 323-38
Ohnuma T, Lehrer D, Ren C, Cho SY, Maniar M, Silverman L, Sung M, Gretz HF, Benisovich V, Navada S, Akahoho E, Wilck E, Taft DR, Roboz J, Wilhelm F, Holland JF

Rigosertib (ON 01910.Na), a synthetic novel benzyl styryl sulfone, was administered to 28 patients with advanced cancer in a Phase I trial in order to characterize its pharmacokinetic profile, determine the dose-limiting toxicities (DLT), define the recommended phase II dose (RPTD) and to document any antitumor activity. Patients with advanced malignant neoplasms refractory to standard therapy were given escalating doses of rigosertib (50, 100, 150, 250, 325, 400, 650, 850, 1,050, 1,375, 1,700 mg/m(2)/24h) as a 3-day continuous infusion (CI) every 2 weeks. An accelerated Fibonacci titration schedule with specified decreases for toxicities was used for escalation until grade ?2 toxicity occurred. Intrapatient dose escalation was allowed if toxicity was grade ?2 and the disease remained stable. Plasma pharmacokinetics (PK) and urinary PK assessments were studied in the 1st and 4th cycles. Twenty-nine patients (12 men and 17 women; age 36-87 y with a median of 63 y) were registered, but one died before study drug was given. Twenty-eight patients received a median of 3 cycles of therapy. Most common grade ?2 toxicities attributable to rigosertib included fatigue, anorexia, vomiting and constipation. DLTs included muscular weakness, hyponatremia, neutropenia, delirium and confusional state. Risk factors for severe toxicities include pre-existing neurological dysfunction or advanced gynecologic cancer after pelvic surgery. Rigosertib pharmacokinetics showed rapid plasma distribution phases and urinary excretion. Elevations in plasma Cmax and AUC due to decreases in plasma clearance were associated with acute grade ?3 toxicities. Of 22 evaluable patients, 9 (41%) achieved a best overall response of stable disease; all other patients (n=13; 59%) progressed. The median progression-free survival time was 50 days (95% confidence interval [CI]: 37-80 days). Nine (41%) patients survived for over 1 y. In summary, prolonged IV infusions of rigosertib were generally well tolerated. Nine (41%) patients achieved stable disease and 9 (41%) patients survived for over 1 year. The RPTD appears to be 850 mg/m(2)/24hr CI x 3 days. (ClinicalTrials.gov identifier: NCT01538537). HubMed – drug