methylcellulose and isosorbide-5-mononitrate

This study aimed to develop and evaluate a novel multi-unit tablet that combined a pellet with a sustained-release coating and a tablet with a pulsatile coating for the treatment of circadian rhythm diseases. The model drug, isosorbide-5-mononitrate, was sprayed on microcrystalline cellulose (MCC)-based pellets and coated with Eudragit(®) NE30D, which served as a sustained-release layer. The coated pellets were compressed with cushion agents (a mixture of MCC PH-200/ MCC KG-802/PC-10 at a ratio of 40:40:20) at a ratio of 4:6 using a single-punch tablet machine. An isolation layer of OpadryII, swellable layer of HPMC E5, and rupturable layer of Surelease(®) were applied using a conventional pan-coating process. Central-composite design-response surface methodology was used to investigate the influence of these coatings on the square of the difference between release times over a 4 h time period. Drug release studies were carried out on formulated pellets and tablets to investigate the release behaviors, and scanning electron microscopy (SEM) was used to monitor the pellets and tablets and their cross-sectional morphology. The experimental results indicated that this system had a pulsatile dissolution profile that included a lag period of 4 h and a sustained-release time of 4 h. Compared to currently marketed preparations, this tablet may provide better treatment options for circadian rhythm diseases.

Topics: Administration, Oral; Angina Pectoris; Cardiovascular Agents; Cellulose; Chemistry, Pharmaceutical; Chronobiology Disorders; Delayed-Action Preparations; Drug Carriers; Excipients; Hypromellose Derivatives; Isosorbide Dinitrate; Kinetics; Methacrylates; Methylcellulose; Microscopy, Electron, Scanning; Polymers; Solubility; Tablets; Technology, Pharmaceutical

We prepared the isosorbide-5-mononitrate pulsatile controlled-release pellets (PCRP) and studied the influencing factors in vitro. The isosorbide-5-mononitrate (5-ISMN) pellets prepared by extrusion-spheronization technology were coated with swelling material as the inner coating swelling layer, and with ethylcellulose aqueous dispersion as the outer coating controlled layer. The influences of the coating materials of the swelling layer, the coating levels of the swelling layer and controlled layer,and the pH values of the media on the release of 5-ISMN from PCRP were investigated. The drug release from the pellets was pulsatile. The ISMN-5-PCRP, with a lag time of 5 h and more than 80% released within the following 1.5 h,were prepared by using the low-substituted hydroxypropyl cellulose as the inner swelling layer with 15% (weight) in coating thickness, and the ethylcellulose aqueous dispersion as the outer controlling layer with 13% (weight) in coating thickness.

Topics: Capsules; Cellulose; Delayed-Action Preparations; Drug Carriers; Hypromellose Derivatives; Isosorbide Dinitrate; Methylcellulose

A 70-year-old woman with acute myocardial infarction (AMI) had a narrow necked left ventricular (LV) aneurysm and pericardial effusion. Although there had been no obvious sign of pseudoaneurysm at the first operation on the 13th day after onset, LV volume increased so dramatically that dyspnea on mild exertion was induced only 2 months after the onset of AMI. She underwent Dor's operation for the expanded LV aneurysm. The histological findings of the resected tissue, which were fibrotic epicardial lesion with small myocyte islands, indicated a true aneurysm. The ultrasound manifestation of a narrow necked aneurysm with abrupt thinning of the myocardium at the hinge point may be a valuable predictor of free wall rupture in the early phase and severely progressive LV remodeling in the late phase. Such aneurysms need to be considered as high risk.

Topics: Aged; Aneurysm, False; Antihypertensive Agents; Combined Modality Therapy; Coronary Disease; Disease Progression; Echocardiography; Endocardium; Female; Fibrin Tissue Adhesive; Heart Aneurysm; Heart Rupture; Heart Ventricles; Humans; Hypromellose Derivatives; Isosorbide Dinitrate; Methylcellulose; Myocardial Infarction; Nitroglycerin; Pericardial Effusion; Stroke Volume; Tissue Adhesives; Ventricular Remodeling