Water-soluble drugs delivery

Drug Release from PHEMA-l-PIB Networks. Amphiphilic networks due to their distinct microphase separated hydrophobic-hydrophilic domain structure posses potential for biomedical applications. Similar microphase separated materials such as poly(HEMA- -styrene-6-HEMA), poly(HEMA-6-dimethylsiloxane- -HEMA), and poly(HEMA-6-butadiene- -HEMA) triblock copolymers have demonstrated better antithromogenic properties to any of the respective homopolymers (5-S). Amphiphilic networks are speculated to demonstrate better biocompatibility than either PIB or PHEMA because of their hydrophilic-hydrophobic microdomain structure. These unique structures may also be useful as swellable drug delivery matrices for both hydrophilic and lipophilic drugs due to their amphiphilic nature. Preliminary experiments with theophylline as a model for a water soluble drug were conducted to determine the release characteristics of the system. Experiments with lipophilic drugs are the subject of ongoing research. 

Delivery to liver and spleen after intravenous injection Bleomycin, water-soluble drugs... 

As with micelle-facilitated dissolution, emulsion-facilitated dissolution has gained renewed interest due to its application to water-insoluble drug delivery and enhanced absorption. Over the years, emulsion systems have been developed and used to either model the in vivo dissolution process or mimic the intestinal surfactant system to enhance drug delivery of poorly soluble compounds [54-66], Emulsions have also been used as vehicles for drug delivery, e.g., to protect... 

Y Yumiko, RD Roberts, VJ Stella. Low-melting phenytoin prodrugs as alternative oral delivery modes for phenytoin A model for other high-melting sparingly water-soluble drugs. J Pharm Sci 72(4) 400-405, 1983. 

Araya H, Tomita M, Hayashi M (2006) The novel formulation design of self-emulsifying drug delivery systems (SEDDS) type O/W microemulsion III The permeation mechanism of a poorly water soluble drug entrapped O/W microemulsion in rat isolated intestinal membrane by the Ussing chamber method. Drug Metab Pharmacokinet 21 45-53. 

Y. Yamaoka, R. D. Roberts, J. V. Stella, Low-Melting Phenytoin Prodrugs as Alternative Oral Delivery Modes for Phenytoin A Model for Other High-Melting Sparingly Water-Soluble Drugs , J. Pharm. Sci. 1983, 72, 400 - 405. 

The experimental procedure below describes the uptake of ciprofloxacin into sphingomyelin (SPM)/Chol LUVs. Drug delivery vehicles prepared from SPM/Chol often exhibit greater efficacy than those prepared from DSPC/Chol (13). Included is a description of the Bligh-Dyer extraction procedure (78), which involves partitioning the lipid and water-soluble drug into organic solvent and aqueous layers, respectively. This is necessary because lipid interferes with the ciprofloxacin assay. 

J.E. Kipp, The role of solid nanoparticle technology in the parenteral delivery of poorly water-soluble drugs, Int. J. Pharm., 284, 109-122 (2004). 

Surfactants are employed in nanoparticle suspensions. Chen et al. (2002) evaluated the pre paration of amorphous nanoparticle suspensions containing cyclosporine A using the evaporative precipitation into aqueous solution (ERAS) system. The effect of particle size was studied varying the drug surfactant ratios, type of surfactants, temperature, drug load, and solvent. Acceptable particle sizes suitable for both oral and parenteral administration were also studied. Additional articles in the nanoparticle delivery of poorly water-soluble drugs include Kipp (2004), Perkins et al. (2000), Young et al. (2000), and Tyner et al. (2004). 

In some cases, low drug solubility may make some delivery platforms better candidates than others. Application of solubilization techniques enables design and development of oral MR dosage forms for poorly water-soluble drugs and can provide more choices and options in designing such a delivery system. 

FIGURE 22.3 Drug-release pro le from a sustained release lipid-based matrix system for delivery of poorly water-soluble drugs. (Modi ed from Technologies Technical/Technology Date Sheet published by Supernus Pharmaceuticals, 2006.)... 

Given the abundance of water-insoluble or poorly water-soluble drugs as well as drugs exhibiting other development challenges such as metabolic and enzymatic instability, the pharmaceutical industry continues to seek solutions to overcome these limitations to develop innovative, clinically safe, and patient-friendly products. As said earlier, MR delivery products offer tremendous advantages with respect to therapeutic indices, pharmacoeconomics, and patient compliance. In addition,... 

Humberstone, A.J., and W.N. Charman. 1997. Lipid-based vehicles for the oral delivery of poorly water soluble drugs. Adv Drug Deliv Rev 25 103. 

Solubilization of poorly water-soluble drugs by complexation with cyclodextrins and then delivery via the buccal or sublingual mucosa has been studied as an additional strategy for increasing drug absorption. Cyclodextrins are able to form inclusion complexes with drugs,... 

In this chapter we will provide a brief overview of the early approaches to bioavailability enhancement by use of simple lipid-based delivery systems (lipid solutions, emulsions etc), and then describe recent progress in the application of self-emulsifying- and microemulsion-based formulations. The effects of lipids on the oral bioavailability of co-administered poorly water-soluble drugs may also be classified from a mechanistic (and to a degree, historical) perspective as physicochemically mediated effects (solubility, dissolution, surface area) and biochemically mediated effects (metabolism, transport related events), and these will be approached separately. It is readily apparent, however, that in many cases physicochemically and biochemically mediated mechanisms will operate side by side. In some instances, bioavailability may also be enhanced by the stimulation of intestinal lymphatic transport, and these studies will be addressed in a separate section. 

Amphiphilic poly(ethylene glycol)-alkyl dextran ethers are emerging as vehicles in the oral delivery of poorly water soluble drugs [251,268,269]. They form polymer micelles of low critical association concentrations (CAC) and small micelle sizes in aqueous solution. Particulate delivery systems lead to an enhancement of the absorption efficiency and bioavailability of highly hpophihc drugs orally applied, and provide the drug with some level of pro-... 

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