Migration of BHT and Irganox 1010 from low-density polyethylene (LDPE) to foods and food-simulating liquids.

The most widely used food-wrapping material is low-density polyethylene (LDPE). Food-wrap grades contain antioxidants to minimize degradation during processing and, in the final films, such additives are normally present at levels of several hundred ppm. During use, the antioxidants may migrate into food stored in LDPE wraps. Two typical antioxidants, BHT and Irganox 1010, were radiolabelled to allow accurate analytical measurement of the extent of their migration into foods and food-simulating liquids (FSL). The results show that BHT, a much smaller and more volatile molecule than Irganox 1010, migrates more rapidly into foods, but the differences are less for FSL. In most instances, migration appears to be controlled by diffusion of the antioxidant in the polymer, and the quantity lost can be correlated in a linear fashion with the square root of time. With aqueous FSL, and, presumably aqueous-type foods, however, anomalies result; the migration is often erratic, but is more closely related to time than to the square root of time. A tentative model developed to explain these facts assumes that the antioxidants decompose in aqueous media and the net migration rate is controlled largely by the rate of chemical decomposition. It is also shown that dry foods can be surprisingly effective sinks for antioxidants under typical storage conditions.

Migration of Irganox 1010 from ethylene-vinyl acetate films to foods and food-simulating liquids.

In a series of experiments on the migration of the antioxidant Irganox 1010 from ethylene-vinyl acetate (EVA) films into food-simulating liquids and foods, the antioxidant was found to migrate rapidly from EVA film into n-heptane, 100% ethanol and corn oil. The rate of migration into these media was greater from EVA than from low-density polyethylene (LDPE) under comparable conditions. In contrast, little migration of Irganox 1010 was recorded on exposure of the EVA film to aqueous media, whereas migration from LDPE into such media was relatively high.

Plasticizer migration from polyvinyl chloride film to solvents and foods.

Polyvinyl chloride (PVC) films used for food wraps contain significant concentrations of plasticizers, along with other additives. The rate of migration of these plasticizers to foods and food-simulating solvents is the principal concern of this paper, which reviews prior experimental studies and presents new data for radiolabelled dioctyl adipate. Analytical models are described to correlate many of the data, criteria are presented for identifying the controlling step in the mechanism of transfer of plasticizer from PVC films into foods and food-simulating solvents, and tentative recommendations are offered for the selection of food simulants and for the type of experiment necessary to allow an unambiguous interpretation of the data.

Use of synthetic polypeptides in the preparation of biodegradable delivery systems for narcotic antagonists.

The goal of this program was the development of biocompatible sustained-release systems that would release naltrexone at a rate of 20 to 25 microgram/hr for 30 days, and that would biodegrade within 90 days. The focus was on the use of macrocapsules prepared from synthetic polypeptides, specifically copolymers of glutamic acid and ethyl glutamate (i.e., Glu/EGlu copolymers). Tubular capsules prepared from 18/82 Glu/EGlu were the most promising systems developed. Capsules 1 cm in length, 0.19 cm in outside diameter, and 0.005 cm in wall thickness released naltrexone in mice at rates in the range of 20 to 40 microgram/hr for 18 days. The rates then decreased during the next 12 days as the capsules became exhausted of drug. These capsules were biocompatible and they appeared to biodegrade within 90 days. In general, the Glu/EGlu copolymers exhibit permeation and degradation rates that increase as the glutamic acid content is increased. Radiotracing studies revealed that the ultimate degradation product was carbon dioxide, which appeared in the expired air. This result is consistent with a polypeptide degradation process that involves hydrolysis of the ethyl esters followed by hydrolysis of the peptide bonds to produce glutamic acid, which enters the metabolic pool.

Indirect food additive migration from polymeric food packaging materials.

Many foods contact polymeric packaging materials which contain residues of the polymerization process or additives employed to facilitate processing. The extent of migration of such materials from the packaging to foods is the focus of the present article. A major experimental program using eight polymer-migrant systems is described. Migration was measured to food-simulating liquids (FSL) and to foods. Accelerated tests were conducted with FSL under FDA guidelines conditions so as to develop correlations between such data and those found using foods under normal storage temperatures and shelf lives. In the majority of tests, the migration was found to be approximately proportional to the square root of time, to increase significantly with a rise in temperature, and to be proportional to the initial concentration of migrant in the polymer. Stirring in the FSL or food phase was generally not important except for the system involving dioctyl adipate migrating from polyvinyl chloride film. In some instances, after a period of time, migration rates became very low, and this effect was attributed to saturating the FSL or food phase with migrant. The foods comprised a variety of types, including liquid, semisolid, solid, and dry; both oily and aqueous foods were included. The physical steps involved in migration include the diffusion of the migrant from the interior of the film to the surface, where it can dissolve in the external FSL or food phase. The nature of the FSL or food is shown to be very important in that components can penetrate the polymer and dramatically increase migration rates. Consistent with the FDA guidelines in effect at the time of this study, testing was performed with five FSL (water, 3% acetic acid, 8% and 50% ethanol, and n-heptane) at 49 degrees C. Detailed comparisons were made between the migrations to foods and to FSL; following are the more relevant conclusions. (1) Three percent acetic acid showed no advantage over water as a food simulant even in those cases where the food could be considered acidic in nature. (2) Water, when used as an FSL at 49 degrees C for 5 days, overestimated migration in aqueous foods in about 75% of the cases. In some instances, however, the water phase became saturated with migrant. In other situations, this test protocol underpredicted migration--especially in those cases where there were components in the food that were able to penetrate into the polymer and enhance migration (such as orange juice).(ABSTRACT TRUNCATED AT 400 WORDS)

Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists.

Synthetic polypeptides consisting of copolymers of glutamic acid and leucine have been shown to be useful materials for the fabrication of practical, biodegradable delivery vehicles for narcotic antagonists. Model delivery vehicles in film form were prepared from copolymers containing 10 mole percent to 40 mole percent glutamic acid, and loaded with 10% to 40% naltrexone by weight. The naltrexone was found to be released by diffusion, exhibiting diffusion coefficients that varied as a function of the glutamic acid content and the initial naltrexone loading. A wide range in diffusion coefficients were achieved (0.31 x 10-7 cm2/hr to 120 x 10-7 cm2/hr), leading to release rates within practical ranges of interest for meeting the program goals. We have demonstrated that the polypeptides can be fabricated into dosage forms that are amenable to administration by trochar. For example, rods 0.4 mm to 0.8 mm in diameter containing as much as 40% naltrexone by weight were extruded using a simple compression mold and die arrangement. An in vitro evaluation of the rods showed that antagonist is released by diffusion at a continuously decreasing rate, a behavior similar to that observed with the film devices that were, nonetheless, capable of blocking an AD80 challenge of morphene sulfate in mice for more than 30 days. One of the most promising delivery vehicles that we have developed to date consists of a polypeptide tube filled with a naltrexone/polypeptide core. Preliminary experiments have shown that these devices may be capable of administering high, constant rates of release for prolonged periods of time. Additional work, however, is required to develop techniques for the preparation of reproducible delivery vehicles.

Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists.

Synthetic polypeptides consisting of copolymers of glutamic acid and leucine have been shown to be useful materials for the fabrication of practical, biodegradable delivery vehicles for narcotic antagonists. Model delivery vehicles in film form were prepared from copolymers containing 10 mole percent to 40 mole percent glutamic acid, and loaded with 10% to 40% naltrexone by weight. The naltrexone was found to be released by diffusion, exhibiting diffusion coefficients that varied as a function of the glutamic acid content and the initial naltrexone loading. A wide range in diffusion coefficients were achieved (0.31 x 10(-7) cm2/hr to 120 x 10(-7) cm2/hr), leading to release rates within practical ranges of interest for meeting the program goals. We have demonstrated that the polypeptides can be fabricated into dosage forms that are amenable to administration by trochar. For example, rods 0.4 mm to 0.8 mm in diameter containing as much as 40% naltrexone by weight were extruded using a simple compression mold and die arrangement. An in vitro evaluation of the rods showed that antagonist is released by diffusion at a continuously decreasing rate, a behavior similar to that observed with the film devices that were, nonetheless, capable of blocking an AD80 challenge of morphine sulfate in mice for more than 30 days. One of the most promising delivery vehicles that we have developed to date consists of a polypeptide tube filled with a naltrexone/polypeptide core. Preliminary experiments have shown that these devices may be capable of administering high, constant rates of release for prolonged periods of time. Additional work, however, is required to develop techniques for the preparation of reproducible delivery vehicles.