Water-soluble drugs

Etoposide (XV) is a semisynthetic gylcoside derivative of podophyllotoxin, which is one of the most extensively used anticancer drugs in the treatment of various types of tumors [64,65]. The anticancer activity of this drug is mainly due to its ability to inhibit an ubiquitous and essential enzyme human DNA topo II [66,67]. Despite its extensive use in the treatment of cancers, it has several limitations, such as poor water solubility, drug resistance, metabolic inactivation, myelosuppression, and toxicity [68]. In order to overcome these... 

Pouton, C. Formulation of poorly water-soluble drugs for oral administration Physicochemical and physiological issues and the lipid formulation classification system. Eur. J. Pharm. Sci. 2006, 29, 278-287. 

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. 

These mixing motions will tend to improve drug absorption for two reasons. Any factor that increases rate of dissolution will increase the rate (and possibly the extent) of absorption, especially for poorly water-soluble drugs (BCS Classes II and IV). Since rate of dissolution depends on agitation intensity, mixing movements will tend to increase dissolution rate and thereby influence absorption. As rate of absorption depends directly on membrane surface area, and since mixing increases the contact area between drug and... 

E Tomlinson, JJ Burger. Incorporation of water-soluble drugs in albumin microspheres. In KJ Widder, R Green, eds. Methods in Enzymology Part A, Drug and Enzyme Targeting. Orlando Academic Press, 1985, pp 27 43. 

The coacervation approach uses heating or chemical denaturation and desolvation of natural proteins or carbohydrates. As much as 85% of water-soluble drugs can be entrapped within a protein matrix by freeze-drying the emulsion prepared in this manner. For water-insoluble drugs, a microsuspension-emul-sion procedure has been suggested as a method of choice to achieve high drug payloads. 

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

Dressman, J. B. Reppas, C., In vitro-in vivo correlations for lipophilic, poorly water-soluble drugs, Eur. J. Pharm. Sci. 11 (Suppl. 2), S73-S80 (2000). 

SS Kornblum, JO Hirschorn. Dissolution of poorly water-soluble drugs I. Some physical parameters related to method of micronization and tablet manufacture of a quinazolinone compound. J Pharm Sci 59 606-609, 1970. 

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. 

The value of Cs is the most critical parameter in determining the overall release rate from a given osmotic system. Indeed, its value will determine whether or not it is feasible to utilize an osmotic system to deliver a particular drug for a specified duration. The maximum release rate achievable is likely that seen with KC1. The relevant values for the parameters in Eq. (6) for OROS [10] are as follows A = 2.2 cm2, h = 0.025 cm, LpO = 2.8 X 10 6 cm2/(atm hr), Us = 245 atm, and Cs = 330 mg/mL. This translates to about 20 mg/hr or about 250 mg over a 24 hr period. This is for a highly water soluble drug with a high osmotic pressure differential. For drugs of moderate solubility—for example,... 

RW Korsmeyer, NA Peppas. Effect of the morphology of hydrophilic polymeric matrices on the diffusion and release of water soluble drugs. J Membrane Sci 9 211-227, 1981. 

S. Yokohama. Common solubilizers to estimate the Caco-2 transport of poorly water-soluble drugs., Int. J. Pharm. 2002, 246, 85... 

Orally administered dosage forms are absorbed into the systemic circulation following dissolution in the GI tract. Because substances must be in solution for the absorption from the GI lumen, the absorption rate of poorly water-soluble drugs is limited by their rate of dissolution. The dissolution rate is affected by the unique physicochemical properties of the drug and by physiological factors the pH, composition, and hydrodynamics of the GI medium. 

Fig. 7 Preparation of water-soluble drug-loaded microspheres using w/o/w emulsion methods...

Good, W. R., Diffusion of Water Soluble Drugs from Initially Dry Hydrogels (R. Kostelnik, Ed.), pp. 139-155. Gordon Breach, New York (1976). 

Reduction of particle size increases the total specific surface area exposed to the solvent, allowing a greater number of particles to dissolve more rapidly. Furthermore, smaller particles have a small diffusion boundary layer, allowing faster transport of dissolved material from the particle surface [58]. These effects become extremely important when dealing with poorly water-soluble drugs, where dissolution is the rate-limiting step in absorption. There are numerous examples where reduction of particle size in such drugs leads to a faster dissolution rate [59-61], In some cases, these in vitro results have been shown to correlate with improved absorption in vivo [62-64]. 

Lipophilic drugs (e.g., opiates and antibiotics) cross more easily than do water-soluble drugs. Certain protein-bound drugs may achieve higher plasma concentrations in the fetus than in the mother. 

Volume of distribution for water-soluble drugs is significantly increased due to edema. Use of dosing guidelines for CKD does not reflect the clearance and volume of distribution in critically ill ARF patients. 

Unchanged passive diffusion and no change in bioavailability for most drugs l Active transport and i bioavailability for some drugs l First-pass extraction and T bioavailability for some drugs i Volume of distribution and T plasma concentration of water-soluble drugs T Volume of distribution and T terminal disposition half-life (t ) for fat-soluble drugs... 

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