[Coating IV. Study on solutions and cellulose films. Influence of plasticizers].
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Biomedical subjects
Publications and source records attributed to M Seiller.
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Polylactic acid nanocapsules of clofibride containing soybean oil (SO) or medium-chain triglycerides (MCT) as the oil core were prepared. The in-vitro drug release kinetic profiles were determined and compared to those of a clofibride submicron emulsion using two different kinetic techniques: the bulk equilibrium reverse dialysis sac technique, and the centrifugal ultrafiltration technique. The former technique was shown to be inadequate for in-vitro kinetic comparison purposes as a result of drug diffusion limitations through the dialysis membrane. The latter technique yielded rapid in-vitro release profiles of clofibride from both emulsion and nanocapsule delivery systems under perfect sink conditions although a consistent lower maximum drug amount was released from the MCT nanocapsules as compared to the corresponding emulsion. This was attributed to the relatively higher aqueous solubility of MCT as compared to SO. This comparative study, carried out, to the best of our knowledge, for the first time, clearly showed that both colloidal carriers behave similarly with respect to drug release despite their different morphological characteristics. The kinetic results clearly exclude either the use of submicron emulsion or of nanocapsules as colloidal controlled release delivery systems for any administration route where perfect sink conditions should prevail.
In this work two w/o/w multiple emulsions composed of soybean oil or medium-chain triglycerides and containing insulin were studied. These emulsions were prepared by means of two-step emulsification procedure. The w/o/w emulsions obtained were stable for at least 6 months of storage at 4-6 degrees C. The yield of encapsulation of insulin was > 95%. The main release mechanism is a swelling-breakdown phenomenon. In vitro, the two w/o/w multiple emulsions were able to protect insulin against enzymatic degradation. These results indicate that multiple emulsions have potential as a carrier of insulin for oral administration.
In this work the biological effects of two w/o/w multiple emulsions composed of the soybean oil (EHS) or medium-chain triglycerides (ETCM), containing insulin, were studied. The release mechanism of insulin from multiple emulsions proposed in our previous in-vitro investigations was confirmed by subcutaneous administration. This mechanism is the swelling-breakdown phenomenon which occurs when the emulsions are diluted under hypo-osmotic condition. The biological effect after oral administration, evaluated in two experimental protocols, single administration in normal and diabetic rats and short-term treatment in diabetic rats, shows that in diabetic rats small amounts of biologically active insulin were absorbed from these emulsions. In these experiments no significant difference between EHS and ETCM was found.
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Although oral L/H emulsions are rare, they constitute interesting pharmaceutical forms. Such systems are easy to administer, are good to protect a fragile lipophilic active substance and are able to modify drug release. After a recall on the principal components frequently used in these forms, such as oils surface active agents and active drugs, the mechanism of bioavailability and influencing factors are detailed. Finally, evaluation methods in order to analyse in vitro release are discussed.