Drug delivery salts

On Recent Advances In Drug Delivery. Salt Lake City, USA... 

Phosphazene polymers can act as biomaterials in several different ways [401, 402,407]. What is important in the consideration of skeletal properties is that the -P=N- backbone can be considered as an extremely stable substrate when fluorinated alcohols [399,457] or phenoxy [172] substituents are used in the substitution process of the chlorine atoms of (NPCl2)n> but it becomes highly hydrolytically unstable when simple amino acid [464] or imidazole [405-407] derivatives are attached to the phosphorus. In this case, an extraordinary demolition reaction of the polymer chain takes place under mild hydrolytic conditions transforming skeletal nitrogen and phosphorus into ammonium salts and phosphates, respectively [405-407,464]. This opens wide perspectives in biomedical sciences for the utilization of these materials, for instance, as drug delivery systems [213,401,405,406,464] and bioerodible substrates [403,404]. 

Nevertheless, there are reports on enhancement of ocular drug absorption by bile salts [33], surfactants [200], and chelators [149], Newton et al. [35] demonstrated that Azone, an enhancer widely tested in transdermal drug delivery [201], increased the ocular absorption of cyclosporine, an immunosuppressant, by a factor of 3, thereby prolonging the survival of a corneal allograft. In 1986, Lee et al. [34] reported that 10 pg/mL cytochalasin B, an agent capable of condensing the actin microfilaments, increased the aqueous humor and iris-ciliary body concentrations of topically applied inulin (5 kDa) by about 70% and 700%, respectively, in the albino rabbit. 

Calcium-responsive drug delivery, 9 64-65 Calcium salt(s)... 

Ulbrich, K. and Oupicky, D. Eighth International Symposium on Recent Advances in Drug Delivery Systems, 1997, pp. 215-218, Salt lake City, UT, February 24-27. 

Contact lenses - [CONTACT LENSES] (Vol 7) -disinfectant for [CITLORINE OXYGEN ACIDS AND SALTS - CH.OROUS ACID, CH.ORITES, AND CHLORINE DIOXIDE] (Vol 5) -disinfectants for [DISINFECTANTS AND ANTISEPTICS] (Vol 8) -methacrylates m [METHACRYLIC POLYMERS] (Vol 16) -PVP hydrogels [VINYL POLYMERS - N-VINYLAMIDE POLYMERS] (Vol 24) -sterilization usingH202 [HYDROGEN PEROXIDE] (Vol 13) -use m drug delivery [DRUG DELIVERY SYSTEMS] (Vol 8)... 

This increase in water solubility on conversion of an amine to its protonated salt has enormous practical consequences in drug delivery. Many important amine-containing drugs, such as morphine (a painkiller) and tetracycline (an antibiotic), are insoluble in aqueous body fluids and are thus difficult to deliver to the appropriate site within the body. Converting these drugs to their ammonium salts, however, increases their solubility to the point where delivery through the bloodstream becomes possible. 

Their mode of appearance in the lumen of the intestine is rather complicated and involves activation of trypsinogen secretion by enterokinase. Once trypsin is formed it activates chymotrypsinogen. Pancreatic lipase is also secreted into the lumen with the pancreatic fluid. The digestion process of fatty acids by their lipase-mediated hydrolysis is completed by bile salts, which are also secreted in the duodenum and are crucial for micellization of lipophilic compounds. The micelles formed in the duodenum enable the absorption of hydro-phobic drugs such as steroids. They pose, however, a serious constraint for the stability of drug delivery carriers such as liposomes and emulsions. 

The new cyclosporine formulation (Sandimmun Neoral, Novartis Pharmaceuticals Corporation, East Hanover, NJ) is a self-microemulsifying drug delivery system, which consists of the drug in a lipophilic solvent (corn oil), hydrophilic cosolvent (propylene glycol) surfactant and an antioxidant [37]. Upon contact with GI fluids, Sandimmun Neoral readily forms a homogenous, monophasic microemulsion, which allows the absorption of the drug molecules. Unlike Sandimmun, the formation of this microemulsion is independent of bile salt activity, and indeed, studies have shown that the absorption of cyclosporine from the new formulation is much less dependent on bile flow [38] and is unaffected by food intake [39],... 

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