Osmotically-controlled systems

Fig. 9 Diagrammatic representation of two types of osmotically controlled systems. Type A contains an osmotic core with drug. Type B contains the drug solution in a flexible bag, with the osmotic core surrounding.

On the basis of the long-standing scientiLc foundation of the C ttDStrolled delivery principles, other osmotically controlled systems have been suggested. Combined with the need to provide... 

Kim, C.-J., Osmotically controlled systems, in Controlled Release Dosage Form Design, C.-J. Kim, ed. Lancaster, PA 2000, Technomic Publishing Company, 229-246. 

Solvent-activated systems either by (a) Osmotically controlled systems or (b) Swelling-controlled systems, and (4) Modulated-release systems. Nevertheless it can be added the fifth category (5) Combined mechanisms because it could be observed drug delivery devices that act by a combination of above mentioned mechanisms. Bajpai schematically further explain cited basics mechanisms of control (Bajpai et al. 2008). 

As may be apparent, there are several formulation factors that inllucnce drug release from osmotically controlled systems, including drug solubility, osmotic pressure, the number and size of the delivery orifice and the physicochemical properties of the semi-permeable membrane. These will be discussed individually next ... 

From Equation 28 it may be observed that the rate of drug release from an osmotically controlled system is directly proportional to the osmotic pressure within the tablet. As a result the osmotic pressure is an important design consideration for these systems. Osmotic pressure is a colligative property and is therefore dependent on the number of ions and molecules in solution. If the solubility of the drug is low, the inherent osmotic pressure within the tablet will be low and therefore the rate of drug release will be low. Under these conditions the inclusion of excipients, e.g., mannitol, sodium chloride, potassium chloride or hydrophilic polymers, is required within the tablet core. Upon dissolution within the tablet the osmotic pressure will increase thereby enhancing the rate of release of the therapeutic agent (a.47, a. 167). 

Osmotic Control. Several oral osmotic systems (OROS) have been developed by the Alza Corporation to allow controUed deHvery of highly water-soluble dmgs. The elementary osmotic pump (94) consists of an osmotic core containing dmg surrounded by a semi-permeable membrane having a laser-drilled deHvery orifice. The system looks like a conventional tablet, yet the outer layer allows only the diffusion of water into the core of the unit. The rate of water diffusion into the system is controUed by the membrane s permeabUity to water and by the osmotic activity of the core. Because the membrane does not expand as water is absorbed, the dmg solution must leave the interior of the tablet through the smaU orifice at the same rate that water enters by osmosis. The osmotic driving force is constant until aU of the dmg is dissolved thus, the osmotic system maintains a constant deHvery rate of dmg until the time of complete dissolution of the dmg. 

GM Zentner, GA McClelland, SC Sutton. Controlled porosity solubility- and resin-modulated osmotic delivery systems for release of diltiazem hydrochloride. J Controlled Release 16 237-244, 1991. 

JL Zingerman, JR Cardinal, RT Chern, J Holste, JB Williams, B Eckenhoff, JT Wright. The in vitro and in vivo performance of an osmotically controlled delivery system-IVOMEC SR Bolus . J Controlled Release 47 1-11, 1997. 

FIG. 18 Idealized flowchart of solution management and control system during direct osmotic treatments of plant or animal materials. 

Modi NB, Wang B, Noveck RJ, et al Dose-proportional and stereospecific pharmacokinetics of methylphenidate delivered using an osmotic, controlled-release oral delivery system. J Clin Pharmacol 40 1141-1149, 2000h... 

Dong, L., V fong, P, and Espinal S., L-OF S)BARDCAP a new osmotic delivery system for controlled release of liquid formulation, poster presentat28tfi International Symposium of Controlled Release of Bioactive Materials, San Diego, June, 2001. 

Controlled release dosage forms typically have one of three different dissolution profiles square root of time or matrix diffusion, zero-order delivery as for erosional dosage forms or osmotic pumps, and zero-order delivery with depletion of the driving force as for a membrane-controlled system. For many controlled release dosage forms, zero-order release may be the holy grail. ... 

Osmotic pressure, a colligative property, depends on the concentration of solute (neutral molecule or ionic species) that contributes to the osmotic pressure. Solutions of different concentrations having the same solute and solvent system exhibit an osmotic pressure proportional to their concentrations. Thus a constant osmotic pressure, and thereby a constant influx of water, can be achieved by an osmotic delivery system that results in a constant release rate of drug. Therefore, zero-order release, which is important for a controlled release delivery system when indicated, is possible to achieve using these platforms. In 1974,... 

The elementary osmotic delivery system consists of an osmotic core containing drug and, as necessary, an osmogen surrounded by a semiper-meable membrane with an aperture (Fig. 7.1). A system with constant internal volume delivers a volume of saturated solution equal to the volume of solvent uptake in any given time interval. Excess solids present inside a system ensure a constant delivery rate of solute. The rate of delivery generally follows zero-order kinetics and declines after the solute concentration falls below saturation. The solute delivery rate from the system is controlled by solvent influx through the semiper-meable membrane. 

Key parameters that influence the design of osmotic controlled drug delivery systems... 

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