Lipase formulations

Lipase Formulations and their Activity and Enantioselectivity in Neat Organic Solvent... 

Changing the E value requires a change of the reaction system such as the solvent, the water activity, and immobilization of the biocatalyst. For instance, it has been reported that lipase immobilized on a hydrophobic carrier makes the E value of C. rugosa lipase less sensitive to changes in water activity than the crude enzyme [66]. Other important parameters influencing enantioselectivity are the temperature, the lipase and the lipase formulation, and structural differences in the substrate molecule. Recently, site-directed mutagenesis has attracted increased attention as a tool for altering lipase enantioselectivity [135]. 

Only one detergent lipase, ie, Lipolase introduced by Novo in 1988, has been marketed. The first household powder detergent containing Upase was introduced in Japan in the same year in Europe and the United States in 1990—1991. Lipase is often incorporated into the new compact powder formulations. 

Lipases have proven to be effective in prespotters and other liquid detergent formulations when used in undiluted form for pretreatment of tough fatty stains. The low water content on the fabric in this situation is believed to be responsible for the high catalytic activity (50). 

An example of the appropriate application of organically-modified silica precursors is alkoxides with an alkyl group. When methyltrimethoxy- or methyl-triethoxysilane (Figure 3.2) was added in formulations to increase the hydro-phobicity of ORMOSILs, it resulted in a better enzymatic activity of lipases immobilized in the alkyl-modified silica than in a hydrophilic matrix fabricated by means ofTEOS alone [51,80,129-133]. Similarly, an increased stability of lipase from Candida antarctica B was observed after its immobilization in a silica matrix... 

The hypothesis that is formulated on the basis of these properties is as follows. The signal for increased thermogenesis, when the body temperature falls, is an increase in the level of catecholamines, probably the local concentration of noradrenaline, which will be increased via stimulation of sympathetic nervous system. The catecholamine increases the activity of triacylglycerol lipase within the brown adipose tissue, by a similar mechanism to that which occurs in white adipose tissue (Chapter 7), i.e. by an... 

The lipase-catalyzed resolutions usually are performed with racemic secondary alcohols in the presence of an acyl donor in hydrophobic organic solvents such as toluene and tert-butyl methyl ether (Scheme 1.3). In case the enzyme is highly enantioselective E = 200 or greater), the resolution reaction in general is stopped at nearly 50% conversion to obtain both unreacted enantiomers and acylated enantiomers in enantiomerically enriched forms. With a moderately enantioselective enzyme E = 20-50), the reaction carries to well over 50% conversion to get unreacted enantiomer of high optical purity at the cost of acylated enantiomer of lower optical purity. The enantioselectivity of lipase is largely dependent on the structure of substrate as formulated by Kazlauskas [6] most lipases show... 

Steatorrhea occurs in patients whose lipase output is at 10% or less of normal. Lipase and other pancreatic enzyme insufficiencies are observed in cystic fibrosis and chronic alcoholic pancreatitis. Patients with various liver diseases may also present with steatorrhea [18]. For these patients, pancreatic enzymes—mainly lipase, protease, and amylase—extracted with alcohol from porcine pancreases have been shown to provide amelioration of diarrhea. These enzymes are enriched and formulated in... 

Pancreatic enzyme supplements are well tolerated. The capsules should be swallowed, not chewed, because pancreatic enzymes may cause oropharyngeal mucositis. Excessive doses may cause diarrhea and abdominal pain. The high purine content of pancreas extracts may lead to hyperuricosuria and renal stones. Several cases of colonic strictures were reported in patients with cystic fibrosis who received high doses of pancrelipase with high lipase activity. These high-dose formulations have since been removed from the market. 

Weight loss aids Orlistat, 60 mg with each meal containing fat (not to exceed 180 mg/d) Alii Approved for weight loss in overweight adults > 18 years of age when used in combination with a reduced-calorie, low-fat diet and exercise program. Orlistat is a nonsystemically absorbed inhibitor of gastrointestinal lipase that blocks the absorption of dietary fat. OTC formulation is a half-strength version of the prescription product (Xenical). 

The efLciency ofthe lipases is dependent on the exposed surface area dictated by the number of droplets and their size in fat emulsions (Turnberg and Riley, 1985 Norkskog et al., 2001 Mu and Usy, 2004). This is one reason for the emphasis on dispersibility of lipid-based formulations as a measure of performance. Lipase activity is also a function ofthe acyl chain lengths, with LCTs hydrolyzed at a slower rate than MCTs (Mu and Usy, 2004). Furthermore, the lipases can be inhibited... 

Pancreatic lipase is rapidly inactivated at pH values less than 4 [25] (Figs. 3 and 5], which has important consequences in the development of galenic formulations for pancreatic enzyme replacement. 

To about 10% of the normal pancreatic secretion, 100,000 FIP units of lipase are required per meal [80]. This means that in order to facilitate patient compliance, foe galenic formulation should contain the maximum amount of panoreatin possible per dose. Earlier studies suggest a minimum of 30,000 FIP units per meal [81], but in recent years higher amounts per meal have been recommended [80,82]. 

Abstract The major enzymatic barrier to the absorption of macromolecules, particularly therapeutic peptides, is the pancreatic enzymes the peptidases, nucleases, lipases and esterases that are secreted in considerable quantities into the intestinal lumen and rapidly hydrolyse macromolecules and lipids. In the case of the peptidases, they work in a co-ordinated fashion, whereby the action of the pancreatic enzymes is augmented by those in the brush borders of the intestinal cells. The sloughing-off of mucosal cells into the lumen also furnishes a mixture of enzymes that are a threat to macromolecules. As the specificity and activity of the enzymes are not always predictable, during pharmaceutical development it is important to test the stability of therapeutic macromolecules, and novel macromolecular-containing or lipid-containing formulations, in the presence of mixtures of pancreatic enzymes and bile salts, or in animal intestinal washouts or ideally, aspirates of human intestinal contents. 

Lipases are enzymes that hydrolyse triglycerides in fats and phospholipases, as the name indicates, hydrolyse phospholipids. Lipases remove long-chain fatty acids from triglycerides, and they are also frequently described as having esterase activity. There are also specific esterases described in the GI tract, for example, carboxylesterase that is secreted by the pancreas. These enzymes are included in the discussion because their activity may be relevant to the use of macromolecular materials in novel formulations, particularly for oral peptide and nucleic acid delivery. 

The stomach also contains an active lipase that can hydrolyse triglycerides and so may start acting against the components of the lipidic formulations that are becoming more common. While this enzyme may be less abundant and less active than pancreatic lipase, there is sufficient activity to substantially initiate lipid hydrolysis (Carriere et al. 2000). 

Given the uncertainties of the quantities and the precise specificities of many digestive enzymes, notably the endopeptidases, and the surprises that biological systems sometimes throw up (who would have expected chitosan to be hydrolysed by pepsin, pancreatin, a lipase or a-amylase as has been reported (Muzzarelli 1997 Muzzarelli et al. 1995 Yalpani and Pantaleone 1994)) any therapeutic macromolecule or formulation destined for oral use should be... 

Importance of Enzyme Formulation for the Activity and Enantioselectivity of Lipases in Organic Solvents... 

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