Osmotic pump

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. 

The simplest osmotic dosage form, ALZA Corporation s OROS elementary osmotic pump (Fig. 7), combines the dmg and sometimes an osmotic agent in a monolithic core and deflvers the dmg in solution (102). The mass dehvery rate with time dm df) of the dmg solution is described by equation 4, where is the hydrauHc permeabiUty of the membrane, a is the membrane reflection coefficient, Atz is the osmotic pressure gradient, APis the hydrostatic back pressure, A is the area of the membrane, C is the dissolved concentration of the dmg, and b is the membrane thickness. 

This equation describes the steady-state, or zero-order, release of the dmg. When the dmg completely dissolves, its concentration within the system begins to dilute, and the release rate foUows a parabohc decline with time (102). Acutrim (ALZA Corp.), dehvering phenylpropanolamine hydrochloride [154-41 -6] for appetite suppression, is an example of an elementary osmotic pump. 

Fig. 8. Example of a Push-Pull osmotic pump where (a) represents the pump before operation, and (b), during operation.

Fig. 10. Stmcture of Push-Melt osmotic pump, developed primarily for veterinary therapeutic appHcations.

Fig. 12. Profile of patterned dehvery of salbutamol, for nocturnal asthma, from an elementary osmotic pump. A delayed pulse of salbutamol, superimposed...

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. 

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

Neural networks have also been used in Slovenia, to model the release characteristics of diclofenac [52] in China, to study release of nifedipine and nomodipine [53] and in Yugoslavia to model the release of aspirin [54], More recently, work in this area has been extended to model osmotic pumps in China [55] and enteric coated tablets in Ireland [56],... 

Wu T, Pao W, Chen J, Shang R. Formulation optimization technique based on artificial neural network in salbutamol sulfate osmotic pump tablets. Drug Dev Ind Pharm 2000 26 211-15. 

There have been recent studies on the importance of NO in modulating skin blood flow in both normal animals and in inflammatory models. Khan etiU. (1993), using laser-Doppler techniques, showed that the NOS inhibitor L-NAME inhibited rabbit ear blood flow. It was possible to do this chronically for up to 2 weeks using implanted osmotic pumps. Pons et id. (1993) also used laser Doppler to show that the vasodilator eflFect of LPS in rabbit skin, which mimics the efiect of Gram-negative bacteria, was likely to involve both i-NOS and IL-1. We have already discussed the damaging eflPects of neutrophils... 

Wu et al. [46] used the approach of an artificial neural network and applied it to drug release from osmotic pump tablets based on several coating parameters. Gabrielsson et al. [47] applied several different multivariate methods for both screening and optimization applied to the general topic of tablet formulation they included principal component analysis and... 

Figure 1 Picture showing the components and mechanism of release for the elementary osmotic pump. (From Ref. 3.)...

Figure 2 In vitro release of KC1 from the elementary osmotic pump with and without stirring of the dissolution medium. The brackets represent the range of the data from five systems. (From Ref. 10.)... 

As noted earlier, perhaps the key determinant of the overall release characteristics from an osmotic pump system is the solubility of the drug. If the solubility of the drug is too low, then the total dose that can be delivered is limited. If the solubility is too high, then the percent of the total dose that can be delivered at a zero-order rate can be relatively small. For example, as shown by Theeuwes [10], the fraction of the total dose (F) that can be delivered at a zero-order rate is given by... 

Numerous other examples of the use of solubility to control the delivery profile of drugs from the elementary osmotic pump can be found in the literature, especially the patent literature [35-40], These systems apply to drugs of moderate to high aqueous solubility where either the excipient or the salt form of the drug was used to control the drug solubility within the core formulation. 

The equations required to describe the release rate from this system are fundamentally the same as those utilized for the elementary osmotic pump. The basic equation is... 

F Theeuwes, D Swanson, P Wong, P Bonson, V Place, K Heimlich, KC Kwan. Elementary osmotic pump for indomethacin. J Pharm Sci 72 253-258, 1983. 

GA McClelland, SC Sutton, K Engle, GM Zentner. The solubility-modulated osmotic pump In vitro/in vivo release of diltiazem hydrochloride. Pharm Res 8 88-92, 1991. 

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. 

BG Kabra, SH Gehrke. Hydrogels for driving an osmotic pump. Polym Prepr 30 490-491, 1989. 

Administration of 17 to homozygous F508del-CFTR mice for 48 h, using a micro-osmotic pump delivery system (50 ig/h), increased the salivary secretion to 6.6% of normal wild-type control mice. Compound 18, an inhibitor of the a-1,2 glucosidase, was reported as a CFTR corrector... 

Theeuwes, F. and Yum, S.I. (1976). Principles of the design and operation of generic osmotic pumps for the delivery of semisolid or liquid drug formulations. Ann. Biomed. Eng. 4 343-353. 

This apparatus has many design configurations, some applying to transdermal patches and others to oral dosage forms, in particular the osmotic pump extended-release tablet. 

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