Oral emulsions

A number of azetidine-based compounds have been disclosed in patent applications from Aventis Pharma for CBi-modulated treatment of diseases such as obesity, Parkinson s disease, schizophrenia, respiratory and neurological diseases [330-334]. Compound (556) was specifically claimed for use in two formulation patent applications [330, 331] for a stable semi-solid composition and oral emulsion composition, respectively. The optional coadministration of an agent that activates norepinephrinergic and se-rotoninergic neurotransmission (for example, sibutramine) or dopaminergic neurotransmission was also claimed for the treatment of obesity. The optional use of a dopamine agonist (for example, levodopa) was claimed... 

In oral formulations, medium-chain triglycerides are used as the base for the preparation of oral emulsions, microemulsions, self-emulsifying systems, solutions, or suspensions of drugs that are unstable or insoluble in aqueous media, e.g. calciferol. Medium-chain triglycerides have also been investigated as intestinal-absorption enhancers and have additionally been... 

GRAS listed. Included in the FDA Inactive Ingredients Guide (oral emulsions, powders, solutions, suspensions, tablets, and... 

The answer is a. (Murray, pp 627-661. Scriver, pp 3897-3964. Sack, pp 121-138. Wilson, pp 287-320.) Vitamins A, D, E, and K are all fat-soluble. The physical characteristics of fat-soluble vitamins derive from the hydrophobic nature of the aliphatic chains composing them. The other vitamins listed are water-soluble, efficiently administered orally, and rapidly absorbed from the intestine. Fat-soluble vitamins must be administered intramuscularly or as oral emulsions (mixtures of oil and water). In intestinal disorders such as chronic diarrhea or malabsorption due to deficient digestive enzymes, fat-soluble vitamins are poorly absorbed and can become deficient. Supplementation of fat-soluble vitamins is thus routine in disorders like cystic fibrosis (219700), a cause of respiratory and intestinal disease that is the likely diagnosis in this child. 

For the small scale preparation of oral emulsions the liquid active substance is added to base gel. The base gel can be... 

The dispersion of a liquid into another liquid with which it is immiscible to obtain a sufficiently physically stable product is only possible by emulsifying or solubilising, using surface-active substances (tensides, surfactants). This process is applied in the preparation of creams and solubilisations. In oral emulsions surface-active substances are not used, but instead viscosity enhancers that possess little surface activity. Below the preparation of emulsirMis and solubilisations is briefly discussed. 

DeSULF SLES-302 DeSULF SLES-303 Stabilizer, foam mineral oil oral emulsions... 

Permeation enhancers are used to improve absorption through the gastric mucosa. Eor example, oral dehvery of insulin (mol wt = 6000) has been reported from a water-in-oH- emulsion containing lecithin, nonesterified fatty acids, cholesterol [57-88-5], and the protease inhibitor aprotinin [9087-70-1] (23). 

Micro emulsions based on a heparin-chitosan complex suitable for oral administration based on ingredients acceptable to humans were studied with or without biologically active ingredients. Appropriate mixing and modifications of these microemulsions lead to nanometer-sized heparin-chitosan complexes [108]. 

An MRL of 0.2 mg/kg/day was derived for acute oral exposure (14 days or less) to trichloroethylene. This MRL was based on the study by Fredriksson et al. (1993) in which mouse pups were dosed by gavage with 0, 50, or 290 mg/kg/day trichloroethylene in a 20% peanut oil emulsion between the ages of 10 and 16 days. Behavioral changes (reduced rearing rate) were noted during tests performed at... 

Iron-deficiency anemia in chronic PN patients may be due to underlying clinical conditions and the lack of iron supplementation in PN. Parenteral iron therapy becomes necessary in iron-deficient patients who cannot absorb or tolerate oral iron. Parenteral iron should be used with caution owing to infusion-related adverse effects. A test dose of 25 mg of iron dextran should be administered first, and the patient should be monitored for adverse effects for at least 60 minutes. Intravenous iron dextran then may be added to lipid-free PN at a daily dose of 100 mg until the total iron dose is given. Iron dextran is not compatible with intravenous lipid emulsions at therapeutic doses and can cause oiling out of the emulsion. Other parenteral iron formulations (e.g., iron sucrose and ferric gluconate) have not been evaluated for compounding in PN and should not be added to PN formulations. 

Mineral Oil Hydraulic Fluids. No studies were located regarding cardiovascular effects in humans after inhalation, oral, or dermal exposure to mineral oil hydraulic fluids. In the only animal study available, histopathological examination of the hearts from rats exposed to <1.0 mg/m3 of the water-in-oil emulsion hydraulic fluid Houghto-Safe 5047F for 90 days, 23 hours/day, showed no treatment-related lesions (Kinkead et al. 1991). 

Aqueous products that are at greatest risk from microbial spoilage include solutions, suspensions, and emulsions for repeated oral, parenteral, or external use and include critical products such as multidose injections and eye drops. Unpreserved products without adequate antimicrobial efficacy should not be presented in containers intended for use on more than one occasion unless justified. When antimicrobial preservatives are used, their efficacy has to be demonstrated using the Ph Eur test for antimicrobial preservative efficacy. Factors to be taken into account in designing a preserved product include the nature of the preservative, its concentration in the product, the... 

The liver appeared to be a target organ for hexachloroethane following oral administration. When one dose of 500 mg/kg was administered in an olive oil aqueous emulsion to male sheep, the levels of glutamate dehydrogenase, sorbitol dehydrogenase, ornithine carbamyl transferase, and aspartate aminotransferase in serum increased in the 2-day period after compound administration and then normalized (Fowler 1969b). Hexachloroethane had no effect on bromsulphthalein uptake from the blood by liver cells, but the transfer of this dye to bile was reduced in sheep exposed to doses of 500-1,000 mg/kg/day. 

A series of thiazole-based DGAT-l inhibitors typified by the highly lipophilic compound 10 was disclosed [33]. This report described a tail-vein injection assay wherein a test compound (10, 30, and lOOmg/kg) and 20% emulsion containing a fatty acid mix were orally administered to male C57BL/6N mouse at 0.3ml/mouse. After 1 h following test compound administration, mice were anaesthetized and... 

Another type of novel mueoadhesive formulations was suggested to be submieron emulsions (o/w), bearing droplets eoated with Carbopol 940. These formulations have been shown to generate a 12-fold enhaneement in rats in the oral bioavailability of the antidiuretie peptide drug desmopressin [91]. 

Ilan, E., Amselem, S., Weisspapir, M., Schwarz, J., Yogev, A., Zawoznik, E., and Friedman, D., Improved oral delivery of desmopressin via a novel vehicle mucoadhesive submicron emulsion, P/jarm. Res., 13 1083-1087 (1996). 

Oral Easy Convenient Acceptable Painless Self-administration possible Inappropriate during vomiting Potential drug-stability problems Interactions with food Possible low availability Patient must be conscious Solutions, syrups, suspensions, emulsions, powders, granules, capsules, tablets... 

Rectal Avoids problems of stability in gastrointestinal tract No first-pass metabolism Useful if oral administration is not possible Unpopular Inconvenient Erratic absorption Irritation Suppositories, enemas (solutions, suspensions, emulsions), foams, ointments, creams... 

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