ABSTRACT
In recent years, oral controlled release (CR) system is most acceptable dosage form by the patients. Drugs having short biological half-life and poor water solubility are the suitable candidate for development of CR system. They include dosage forms for oral and transdermal administration as well as injectable and implantable systems. For most of drugs, oral route remains as the most acceptable route of administration. Certain molecules may have low oral bioavailability because of solubility or permeability limitations. Development of an extended release dosage form also requires reasonable absorption throughout the gastro-intestinal tract (GIT). Among the available techniques to improve the bioavailability of these drugs fabrication of osmotic drug delivery system is the most appropriate one. The release of drug(s) from osmotic systems follows zero order. It is mainly governed by various formulation factors such as solubility and osmotic pressure of the core component(s), size of the delivery orifice, and nature of the rate-controlling membrane. The present review highlights an overview of OCDDS. And new technologies, fabrication and recent clinical research in osmotic drug delivery. Further, the challenges of these technologies and its future perspective are also discussed at length.
ABSTRACT
Objective To examine the effects of exogenously administered intermedin (IMD,adrenomedullin-2) on arterial blood pressure,cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats (SHRs) as well as to investigate the associated mechanisms.Methods Thirteen week-old male rats were divided in Wistar Kyoto (WKY) group (n =12),SHR group (n =12),IMD group (SHRs infused with IMD 1-47 500 ng/kg per hour,n =12),and ADM group (SHRs infused with adrenomedullin 500 ng/kg per hour,n =12).Results A two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure,the maximal rates of increase and decrease of left-ventricle pressure development (LV ± dp/dtmax),left ventricular systolic pressure and heart rate in SHRs.Furthermore,IMD also inhibited protein over-expression of cardiovascular IMD receptors,myocardial Receptor Activity-Modifying Proteins (RAMP1 and RAMP2),aortic RAMP1,RAMP2,RAMP3,and calcitonin receptor-like receptor (CRLR);suppressed up-regulation of aortic RAMP1,RAMP2,RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide (ANP) and myocardial brain natriuretic peptide (BNP).Additionally,IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration.Conclusion These findings support the speculation that IMD,as a cardiovascular active peptide,is involved in blood pressure reduction and cardiac function amelioration during hypertension.The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR,and consequential regulation of cAMP levels and other cardiovascular active factors,such as ANP and BNP.
ABSTRACT
As the typical example of controlled release preparation, osmotic pump-controlled release preparation is a new technique of preparation characterized by zero order release kinetics. Osmotic pressure is the motivation for releasing drug. The release behavior of osmotically controlled release systems is independent of external pH and food, and the in vivo-in vitro correlation is good, so they have attracted wide attention at home and abroad. After years of development, with the constant innovation of the mechanism, the structure of the osmotic pump has been continuously improved, and many products have been marketed. In this article, the development history and the mechanism of osmotic pump-controlled release preparation are briefly reviewed. Based on solubility, osmotic pressure, the delivery orifice and the coating membrane, the critical factors affecting the release rate and the research progress on osmotic pump controled release preparation are mainly discussed.