Modulated drug delivery systems

McClelland, G.A. and Zentner, GM., Solubility modulated drug delivery system, US Patent 4946686, 1990. 

Patil, J. S., Kamalapur, M. V., Marapur, S. C., and Kadam, D. V. Ionotropic gelation and polyelectrolyte complexation the novel techniques to design hydrogel particulate, sustained, modulated drug delivery system A review. Digest J. Nanomat. Biostruct. 5(1) (2010) 241-248. 

A photothermal modulated drug delivery system in which near IR fight of a specific wavelength can be used to induce the collapse of a polymeric matrix loaded with model drug molecules and proteins was reported by Bikram et al. (2007). 

Figure 1 Schematic illustration of an ideal stimuli-modulated polymeric drug delivery system.

In this study, we demonstrate new pH/temperature-sensitive polymers with transitions resulting from both polymer-polymer and polymer-water interactions and their applications as stimuli-responsive drug carriers [22-23], For this purpose, copolymers of (Ai,Ai-dimethylamino)ethyl methacrylate (DMAEMA) and ethylacrylamide (EAAm) [or acrylamide (AAm)] were prepared and characterized as polymeric drug delivery systems modulated for pulsatile and time release. 

A buccal drug delivery system is applied to a specific area on the buccal membrane. Moreover, the delivery system ean be designed to be unidirectional in drug release so that it can be protected from the loeal environment of the oral cavity. It also permits the inclusion of a permeation enhancer/protease inhibitor or pH modifier in the formulation to modulate the membrane or the tablet-mucosal environment at that particular application site. While the irritation is limited to the well-defined area, the systemic toxicity of these enhancers/inhibitors and modifiers can be reduced. The buccal mucosa is well suited for this type of modification as it is less prone to irreversible damage [9]. In the event of drug toxicity, delivery can be terminated promptly by removal of the dosage form. 

Sershen S, West J. Implantable, polymeric systems for modulated drug delivery. Adv Drug Deliv Rev. 2002 54 1225-1235. 

Zentner, G. M., McClelland, G. A., and Sutton, S. C. Controlled porosity solubility- and resin-modulated osmotic drug delivery systems for release of diltiazem hydrochloride. J. Contr. Rel. 16(l-2) 237-243, 1991. 

F. Modulation of Pulmonary Selectivity by Sustained-release Drug Delivery Systems... 

Chien YW. Controlled- and modulated-release drug-delivery systems. In Swarbrick J, Baylan JC, eds. Encyclopedia of Pharmaceutical Technology. New York Dekker, 1999 281-313. 

In this review efflux pump inhibitors are classified into two groups low molecular mass inhibitors and polymeric inhibitors, because the high molecular mass of the polymeric excipients prevents absorption into systemic circulation after oral administration. In some cases, just a local inhibition of efflux transporters in the intestine is desired, whereas in other cases also an additional systemic modulation of efflux pumps can be of advantage. For chronical treatments, impact on the complex systemic efflux transporter system can result in severe complications. In this case, an enhanced intestinal absorption of efflux pump substrates can be achieved by using drug delivery systems based on polymeric inhibitors. On the other hand, in cancer therapy it would be of advantage to reduce efflux of anticancer compounds also in the systemic system because tumour tissues often overexpress these transporters. Then a low molecular mass efflux inhibitor could be useful. 

Some naturally occurring polymers have been reported to exhibit efflux pump modulating properties. For example, a drug delivery system based on chitosan has been shown to nearly double the oral bioavailability of the P-glycoprotein substrate rhodamine 123 in vivo in rats in comparison with buffer control (Foger et al. 2006c). 

In summary it can be said that there are a lot of possibilities available to overcome the efflux pump-mediated absorption barrier in the intestinal tract. Further, more selective or more potent inhibitors will follow but it has to be carefully decided for each drug or therapy which type or class of inhibitor or efflux pump modulator might be best suited. Also drug delivery systems combining different efflux pump modulating properties have to be investigated in the future. 

Modulation of GI Transit Time To modulate the GI transit time so that the drug delivery system developed can be transported to a target site or to the... 

Savastano, L., Leuenberger, H., and Merkle, H. P. (1995), Membrane modulated dissolution of oral drug delivery systems, Pharm. Acta Helv.,10,117-124. 

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