Lipophilic formulation

Studies conducted by different authors on the release of chemical substances from medical devices, mainly those used for infusing solutions, show that these are potential sources of contamination for pharmaceutical formulations. One of the most studied is diethylhexyl phthalate, the same plasticizer found in PVC infusion bags to give flexibility. The same concerns about the use of PVC bags for the storage of lipids or lipophilic formulations are valid for tubing. 

Vijayaraghavan, R., Kumar, P., Dubey, D.K., Ram Singh. (2001b). Evaluation of CC2 as a decontaminant in various hydrophilic and lipophilic formulations against sulphur mustard. Biomed. Environ. Set 15 25-35. 

The first example of novel packaging design approaches is a multidose eye-drop pack containing an aqueous solution of a drug used for the treatment of allergic conjunctivitis. The drug is a polar, ionic compound, available as the sodium salt, which is highly water-soluble and has a low lipophilicity. Formulation details are as follows ... 

It is, thus, of first importance to be able to identify a system of this type, not only if a bicontinuous microemulsion is to be manufactured but also if other neighboring systems such as hexagonal, percolated sphere, or dispersed sphere microemulsions are sought. These systems may be attained starting with a Type III system and slightly changing the water-to-oil ratio, the hydrophilic-lipophilic formulation or R ratio, the surfactant or alcohol type, structure and relative concentration, or incorporating polymers or other additives. Extensive experimental studies carried out for both ionic and nonionic surfactant systems showed that the optimum formulation was attained whenever a certain condition between the formulation variables, so-called correlation for optimum formulation, was satisfied. This let to the discovery of empirical correlations between the so-called formulation variables that defined the physical-chemistry situation of the system. 

Skin. The skin may become contaminated accidentally or, in some cases, materials may be deHberately appHed. Skin is a principal route of exposure in the industrial environment. Local effects that are produced include acute or chronic inflammation, allergic reactions, and neoplasia. The skin may also act as a significant route for the absorption of systemicaHy toxic materials. Eactors influencing the amount of material absorbed include the site of contamination, integrity of the skin, temperature, formulation of the material, and physicochemical characteristics, including charge, molecular weight, and hydrophilic and lipophilic characteristics. Determinants of percutaneous absorption and toxicity have been reviewed (32—35,42,43,46—49). 

In most cases, these active defoaming components are insoluble in the defoamer formulation as weU as in the foaming media, but there are cases which function by the inverted cloud-point mechanism (3). These products are soluble at low temperature and precipitate when the temperature is raised. When precipitated, these defoamer—surfactants function as defoamers when dissolved, they may act as foam stabilizers. Examples of this type are the block polymers of poly(ethylene oxide) and poly(propylene oxide) and other low HLB (hydrophilic—lipophilic balance) nonionic surfactants. 

Cleaning solution formulations may include one or more deposit removers, plus an appropriate corrosion inhibitor (to protect exposed metal). An antifoam and often a wetting agent [e.g., an alkylarylpoly-ethoxy alcohol with a 12-15 hydrophilic-lipophilic balance (HLB) to improve detergency and solubilization] may also be added. 

Topical Formulations. Topical formulations by their very nature are usually multicomponent, and it is not surprising that neural networks have been applied to deal with this complexity. The first work was performed on hydrogel formulations containing anti-inflammatory drugs in Japan in 1997 [57], followed up by further studies in 1999 [58] and in 2001 [59]. Lipophilic semisolid emulsion systems have been studied in Slovenia [60, 61] and transdermal delivery formulations of melatonin in Florida [62]. In all cases, the superiority of neural networks over conventional statistics has been reported. 

Because most food matrices are water soluble, many efforts were directed to the formulation of lipophilic pigments (mainly carotenoids) into water-soluble formulations (powders or gels). For hydrophilic pigments like flavonoids, polar dried microcapsules are the most popular ways to stabilize their functionality. Extracts rich in P-carotene were encapsulated using three different encapsulation techniques (spray drying, drum drying, and freeze drying)." ... 

Natural pigments are formulated either as dyes (hydrophilic powders or lipophilic oleoresins) or lakes. 

Cannabinoids are highly lipophilic compounds making bioavailabihty very dependent on the formulation and the mode of administration. Cannabinoid occurrence in the plant is predominantly in the form of the carboxyhc acids, which are pharmacologically totally different and rather unstable, decarboxy-lating over time to their active neutral form. The carboxyhc acids, although not active at the CB receptor, nevertheless add to the overall effect as they possess antibiotic and anti-inflammatory effects. 

These observations can be formulated into the following mechanistic model. In general, the flux of a solute across a cell membrane is determined by the balance of water-solute and membrane-solute forces. For lipophilic solutes, the principal driving force for transfer from water to the membrane will be the... 

Instead of using the oral bioavailability of a drug, one can attempt to correlate PM values with permeability coefficients generated from in situ perfused intestinal preparations. Here, one eliminates the complexities of liver metabolism, clearance, and formulation variables. Recently, this type of in vitro-in situ correlation has been conducted using the model peptides (described previously in Section V.B.2). The permeabilities of these model peptides were determined using a perfused rat intestinal preparation which involved cannulation of the mesenteric vein (Kim et al., 1993). With this preparation, it was possible to measure both the disappearance of the peptides from the intestinal perfusate and the appearance of the peptides in the mesenteric vein. Thus, clearance values (CLapp) could be calculated for each peptide. Knowing the effective surface area of the perfused rat ileum, the CLapp values could be converted to permeability coefficients (P). When the permeability coefficients of the model peptides were plotted as a function of the lipophilicity of the peptides, as measured by partition coefficients in octanol-water, a poor correlation (r2 = 0.02) was observed. A better correlation was observed between the permeabilities of these peptides and the number of potential hydrogen bonds the peptide can make with water (r2 = 0.56,... 

As has been pointed out earlier in this chapter, the dietary consumption and historical medicinal use of carotenoids has been well documented. In the modern age, in addition to crocin, 3.7, and norbixin, 3.8, several carotenoids have become extremely important commercially. These include, in particular, astaxanthin, 3.6 (fish, swine, and poultry feed, and recently human nutritional supplements) lutein, 3.4, and zeaxanthin, 3.3 (animal feed and poultry egg production, human nutritional supplements) and lycopene, 3.2 (human nutritional supplements). The inherent lipophilicity of these compounds has limited their potential applications as hydrophilic additives without significant formulation efforts in the diet, the lipid content of the meal increases the absorption of these nutrients, however, parenteral administration to potentially effective therapeutic levels requires separate formulation that is sometimes ineffective or toxic (Lockwood et al. 2003). 

The problems of high lipophilicity and subsequent low bioavailability of the perylenequinones have been approached by altering their formulations [23]. Another limitation to the use of perylenequinones as therapeutic agents is the poor extinction coefficient in the longer wavelength of light (650-800 nm) that is needed to penetrate deep tissue. Many derivatives of hypocrellin have been... 

Let us consider, for instance, the response mechanism of a polycation-selective galvanostatically controlled sensor. The polymeric membrane is in contact with a NaCl solution. The membrane of the sensor is formulated with a lipophilic salt, for instance, tetradodecylammonium dinonylnaphthalenesulfonate (TDDA-DNNS), which has a relatively high affinity to protamine. Even though protamine is presented in the sample, spontaneous extraction does not take place due to the high lipophilicity of TDDA-DNNS, thus the initial concentration of protamine or sodium cations in the membrane is close to zero. 

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