Drugs surface activity

EFFECTS OF DRUG SURFACE ACTIVITY ON FORMULATION STRUCTURE AND STABILITY... 

Both surface activity and micellization have implications on the biological efficacy of many drugs. Surface-active dmgs tend to bind hydrophobically to proteins and other biological macromoleules. They tend to associate with other amphipathic molecules such as other drugs, bile salts, or with receptors. 

Some biological consequences of drug surface activity... 

Besides trace metals, adsorptive stripping voltammetry has been shown to be highly suitable for measuring organic compounds (including cardiac or anticancer drugs, nucleic acids, vitamins, and pesticides) that exhibit surface-active properties. 

Two main apoptotic pathways have been identified in mammalian cells the extrinsic pathway that is activated by the binding of ligands to cell-surface death receptors, and the intrinsic pathway that involves the mitochondrial release of cytochrome cP The activation of extrinsic and intrinsic apoptotic pathways promotes the cleavage into the active form of the pro-caspase-8 and pro-caspase-9, respectively, that mainly determine the activation of effector caspase-3. ° The intrinsic pathway is the main apoptotic pathway activated by chemotherapeutic drugs, while the cytotoxic drug-induced activation of the extrinsic pathway is a more controversial issue. ... 

Microelectronic circuits for communications. Controlled permeability films for drug delivery systems. Protein-specific sensors for the monitoring of biochemical processes. Catalysts for the production of fuels and chemicals. Optical coatings for window glass. Electrodes for batteries and fuel cells. Corrosion-resistant coatings for the protection of metals and ceramics. Surface active agents, or surfactants, for use in tertiary oil recovery and the production of polymers, paper, textiles, agricultural chemicals, and cement. 

The possession of surface activity per se may be an important faetor in the antibacterial action of a group of drugs, for example the eationie detergents. The addition of low concentrations of surface-active compounds may potentiate the biological effect of an antibacterial agent. Thus, phenols are often more aetive in the presence of soaps. 

Suomalainen, P., Johans, G., Soderlund, T., Kinnunen, P. K. Surface activity profiling of drugs applied to the prediction of blood-brain barrier permeability. J. Med. Chem. 2004, 47, 1783-1788. 

K Kakemi, T Arita, S Muranishi. Absorption and excretion of drugs. XXVII. Effect of nonionic surface-active agents on rectal absorption of sulfonamides. Chem Pllarm Bull 13 976-985, 1965. 

In summary, it is the effective surface area of a drug particle that determines its dissolution rate. The effective surface area may be increased by physically reducing the particle size, by adding hydrophilic diluents to the final dosage form, or by adding surface-active agents to the dissolution medium or to the dosage form. 

A surfactant is a surface-active agent that is used to disperse a water-insoluble drug as a colloidal dispersion. Surfactants are used for wetting and to prevent crystal growth in a suspension. Surfactants are used quite extensively in parenteral suspensions for wetting powders and to provide acceptable syringability. They are also used in emulsions and for solubilizing steroids and fat-soluble vitamins. 

These general observations have been confirmed in PAMPA measurements in our laboratory, using the 2% DOPC-dodecane lipid. With very lipophilic molecules, glycocholic acid added to the donor solution slightly reduced permeabilities, taurocholic acid increased permeabilities, but SLS arrested membrane transport altogether in several cases (especially cationic, surface-active drugs such as CPZ). 

Ledwidge, M. T. Corrigan, O. I., Effects of surface active characteristics and solid state forms on the pH solubility profiles of drug-salt systems, Int. J. Pharm. 174, 187-200 (1998). 

M Gibaldi, S Feldman, ND Weiner. Hydrodynamics and diffusional considerations in assessing the effects of surface active agents on the dissolution rate of drugs. Chem Pharm Bull 18 715-723, 1970. 

A summary of how physiological factors affect the dissolution rate is given in Table 21.2. The effective surface area will be affected by the wetting properties of the bile acids and other surface-active agents in the gastrointestinal tract. The dif-fusivity of a drug molecule in the intestinal juice will be altered by changes in viscosity that are induced, for instance, by meal components. An increased dissolution rate could be obtained at more intense intestinal motility patterns or increased... 

Other surface-active compounds self-assemble into bilayer structures (schematically illustrated in Fig. 10b), which normally spherilize into structures termed vesicles. When vesicles are formed from phospholipids, the term liposome is used to identify the structures, which also provide useful drug delivery systems [71]. Solutes may be dispersed into the lipid bilayer or into the aqueous interior, to be subsequently delivered through a variety of mechanisms. Liposomes have shown particular promise in their ability to act as modifiers for sustained or controlled release. 

Surface-active polar molecule, 15 213 Surface activity, drug efficacy and,... 

Surface-active agents used as adjuvants in pharmaceutical preparations to improve drug dissolution may affect the stability of /3-lactams. Thus, the presence of micelles of cetyl(trimethyl)ammonium bromide (CTAB) enhanced up to 50-fold the rate of alkaline hydrolysis of penicillins [140]. In the case of cephalosporins, micelle-promoted catalysis of the intramolecular degradation process (see Sect 5.2.2) was also observed [85][141], It has been proposed that the negatively charged penicillins and cephalosporins are attracted by the cationic micelles. This attraction increases substrate concentration in the micellar phase, in turn accelerating the rate of HO- ion attack. Ion exchange at the micellar surface and electrostatic stabilization of the transition state may also contribute to the increased rate [142][143],... 

In drug studies, of main interest is the application of colloidal systems, which show specific and unspecific interaction with mainly lipophilic substances. An obvious application is the study of highly lipophilic and poorly absorbable drugs that are administered orally or transdermally (2). Such interactions with surface-active agents may either cause a diminution of the... 

Any conclusions about the organization of different components within the dispersions should take the ultrastructure of the systems into consideration. The surface-active agents that act as stabilizers for the nanoparticles are often able to form additional colloidal structures, such as vesicles or micelles, by self assembly. In addition to a potential importance in the formation and stability of the dispersions, such structures contain lipophilic domains that may represent alternative compartments for the localization of incorporated drugs. As a consequence, their presence may affect drug incorporation and release. 

Finally, surfactants that break down into non-surface active products in a controlled way may find use in speciahzed applications, such as in the biomedical field. For instance, cleavable surfactants that form vesicles or microemulsions can be of interest for drug dehvery, provided the metabolites are nontoxic. 

Organizational characteristics of surface-active molecules have been studied by several researchers due to their applications in many areas such as personal care, polymerization, catalysis, drug delivery, separation and purification, enhanced oil recovery and lubrication. The structure of supramolecular organized assemblies formed in different solvents, when a critical concentration is exceeded, determines their properties such as solubilization [1-3], catalysis [1,4-6], adsorption [7-11] and flocculation [12,13]. As such, many techniques have been used to determine their structural properties. In this paper, the results obtained using fluorescence probing for properties of assemblies in solution and at solid-liquid interfaces are discussed in detail after a brief review of relevant assemblies formed by them. 

It is therefore apparent why the physical chemistry of surfaces and the structure and activity of surface-active agents are also of interest to the medicinal chemist. Antimicrobial detergents and many disinfectants exert their activity by interacting with biological surfaces and are important examples of surface-active drug effects. 

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