Osmotic-controlled release

Modi NB, Lindemulder B, Gupta SK Single- and multiple-dose pharmacokinetics of an oral once-a-day osmotic controlled-release OROS (meth-ylphenidate HCL) formulation. J Clin Pharmacol 40 379-388, 2000a... 

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... 

To give the semipermeable membrane flexibility, plasticizers such as phthalates (dibenzyl, dihexyl, or butyl octyl), triacetin, epoxidized tal-late, or tri-isoctyl trimellitate are added.18 In the design of osmotic controlled release systems, these plasticizers help to modulate and achieve the required release rate. 

Other strategics to enhance the solubility of poorly soluble drugs for use in osmotically controlled release systems have been described by Chien (a.47) and Verma and co-workers (a. 1.59). 

FIGURE 7 Mechanism of action of a Rose-Nelson osmotic pump, the precursor of today s osmotic controlled release delivery systems. 

Risperidone free base preparations include film-coated tablets (1, 2, 3, 4 and 6 mg), orodispersible tablets (0.5, 1, 2, 3 and 4 mg), liquids at 1 mg/mL and depot preparations. Paliperidone is available as free base tablets (3, 6 and 9 mg), the hexadecanoate (palmitate) and extended release formulation using an osmotic-controlled release oral delivery system. 

In open fibers the fiber wall may be a permselective membrane, and uses include dialysis, ultrafiltration, reverse osmosis, Dorman exchange (dialysis), osmotic pumping, pervaporation, gaseous separation, and stream filtration. Alternatively, the fiber wall may act as a catalytic reactor and immobilization of catalyst and enzyme in the wall entity may occur. Loaded fibers are used as sorbents, and in ion exchange and controlled release. Special uses of hoUow fibers include tissue-culture growth, heat exchangers, and others. 

Fig. 6. Schematic representation of the elementary osmotic pump containing a reservoir of dmg for controlled release and an immediately available overcoat...

In these systems, osmotic pressure provides the driving force to generate controlled release of drug. Consider a semipermeable membrane that is permeable to water, but not to drug. A tablet containing a core of drug surrounded by such a membrane is shown in Fig. 9. When this device is exposed to water or any body fluid, water will flow into the tablet owing to the osmotic pressure difference. The rate of flow, dV/dt, of water into the device can be represented as... 

Controlled Release Osmotic Dmg Delivery Systems for Oral Applications... 

Zentner and coworkers [24,26] utilized this information in their development of a system that releases this drug over a 24 hr period. The use of NaCl to modulate the release of diltiazem presents an interesting problem in that the concentration of the solubility modifier must be maintained within certain limits and below its saturation solubility within the device. To solve this problem, core formulations were developed that contained both free and encapsulated NaCl. The encapsulated NaCl was prepared by placing a microporous coating of cellulose acetate butyrate containing 20 wt% sorbitol onto sieved NaCl crystals. The coated granules released NaCl over 12-14 hr period via an osmotic mechanism into either water or the core tablet formulation. The in vitro release profile for tablets (core I devices) containing 360 mg of diltiazem HC1 and 100 mg of NaCl equally divided between the immediate release and controlled release fractions... 

This system is the only osmotic system developed commercially at this time that is suitable for the oral administration of insoluble drugs to humans. It has been utilized in the development of several other drugs including isradipine, doxazosin, diltiazem, contraceptive steroids, glipizide, and verapamil [48-53], The system has also been utilized to codeliver the free bases of compounds normally administered as water-soluble salts such as pseudoephedrine and bromo-pheniramine [54], The latter system includes both a loading dose and a controlled release dose and is intended for applications in the over-the-counter market. 

G Santus, RW Baker. Osmotic drug delivery A review of the patent literature. J Controlled Release 35 1-21, 1995. 

SM Herbig, JR Cardinal, RW Korsmeyer, KL Smith. Asymmetric-membrane tablet coatings for osmotic drug delivery. J Controlled Release 35 127-136, 1995. 

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. 

AG Thombre, JR Cardinal, AR DeNoto, DC Gibbes. Asymmetric membrane capsules for osmotic drug delivery. II. In vitro and in vivo performance. J Controlled Release 57 65-73, 1999. 

DG Pope, PK Wilkinson, JR Egerton, J Conroy. Oral controlled release delivery of ivermectin in cattle via an osmotic pump. J Pharm Sci 74 1108-1110, 1985. 

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. 

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