ethyl-cellulose and Body-Weight

Surelease Aqueous Ethylcellulose Dispersion is an excipient used as a modified release coating for beads, granules, non-pariels, drug crystals and tablets and for taste masking applications for drug products and dietary supplement products. A study was conducted to assess the toxicity of spray-dried Surelease when administered orally, via dietary admixture, to Sprague-Dawley CD rats (20/sex/group) at dose levels of 0, 2000, 3500, and 5000 mg/kg/day for a period of at least 3 months. After 3 months of treatment, all rats scheduled for terminal sacrifice were killed and selected organs were weighed. Complete macroscopic examinations and histopathological evaluation of selected tissues were conducted on all animals. Neuropathological evaluations were performed on 5 animals/sex/group. No mortality occurred during the study. Clinical observations, ophthalmology, body weight and food consumption, hematology, coagulation, clinical chemistry, urinalysis, functional observational assessments, motor activity, organ weights and ratios and macroscopic and microscopic observations did not reveal any significant, consistent, dose-dependent test article-related adverse effects. The NOAEL (no-observed-adverse-effect-level) is 5000 mg/kg/day, the highest dose tested. A series of genotoxicity tests were conducted with Surelease. Surelease showed no evidence of mutagenic activity in the bacterial reverse mutation test with and without metabolic activation and in the in vitro cell mutation assay under the experimental conditions employed. Surelease did not show any evidence of causing chromosome damage or bone marrow cell toxicity when administered by gavage in the mouse micronucleus in vivo test procedure. These findings support the safety of Surelease for use as an excipient.

Topics: Animals; Behavior, Animal; Blood Coagulation; Body Weight; Cellulose; Chemistry, Pharmaceutical; Diet; Eating; Excipients; Female; Lymphoma; Male; Mice; Micronucleus Tests; Mutagenicity Tests; Mutagens; Nervous System Diseases; Organ Size; Pregnancy; Rats; Rats, Sprague-Dawley; Salmonella typhimurium

Groups of 20 male and 20 female Sprague-Dawley rats were administered undiluted Aquacoat ECD ethylcellulose aqueous dispersion by oral gavage at doses of 903, 2709 or 4515 mg/kg body weight/day (dry weight basis) for 90 days. Control animals received water at the same dosage volume as the high-dose group. Body weights and food consumption were recorded weekly. Blood was collected prior to study termination for haematology and clinical chemistry measurements. Survivors underwent complete necropsies on days 91 94. Selected organs were weighed and histologically examined. The only treatment-related clinical sign observed was pale faeces which was noted among males and females receiving 2709 and 4515 mg/kg/day Aquacoat ECD. No statistically significant differences in body weights, body weight gains, food consumption and organ weights were noted among males and females when compared with controls. No treatment-related effects in haematology parameters were noted. Significantly decreased total protein and globulin levels and increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in male rats receiving 2709 and 4515 mg Aquacoat ECD/kg/day were considered to be treatment related. No gross or microscopic lesions were attributed to Aquacoat ECD treatment. Under the conditions of this study, the no-observed-adverse-effect level (NOAEL) for female rats is in excess of 4515 mg/kg/day: the NOAEL for male rats is 903 mg/kg/day.

Topics: Administration, Oral; Alanine Transaminase; Animals; Aspartate Aminotransferases; Body Weight; Cellulose; Eating; Excipients; Female; Male; No-Observed-Adverse-Effect Level; Organ Size; Rats; Rats, Sprague-Dawley; Suspensions

Hydroxypropylcellulose (HPC)-ethylcellulose (EC) microcapsules containing piretanide prepared by a solvent evaporation technique, were evaluated on pharmacokinetic, pharmacodynamic and pharmacological parameters in spontaneously hypertensive rats (SHR). HPC-EC10 (5:3) microcapsules showed sustained plasma piretanide levels and almost the same AUC (area under the curve) as compared with piretanide solution. Effect of treatment with the microcapsules (single oral administration per day in doses of 10 and 30 mg/kg) and the solution (double oral administration per day in doses of 5 and 15 mg/kg) was examined for 4 weeks on urine volume and urinary electrolytes excretion and blood pressure. The microcapsules and solution induced dose-dependent diuresis throughout the experimental period and a reduction in blood pressure from 2 weeks of the treatment. HPC-EC10 (5:3) microcapsules containing piretanide were satisfactory as a sustained-release preparation in the light of the anti hypertensive effect even at a half frequency of daily dosing of the solution.

Topics: Administration, Oral; Aldosterone; Animals; Blood Pressure; Body Weight; Cellulose; Diuretics; Drug Administration Schedule; Drug Compounding; Heart Rate; Hypertension; Male; Rats; Rats, Inbred SHR; Renin; Sulfonamides