Etude de la compressibilite, de la comprimabilite, de la permeabilite aux solutes et de la degradation enzymatique de l'amidon reticule a haute teneur en amylose (French text).

摘要

Natural and synthetic polymers are widely used in pharmaceutical technology, particularly in drug controlled release systems (CRS). A great number of these polymers are accepted today by the regulatory agencies and can be used in pharmaceutical formulations. Recently, a crosslinked high amylose starch (CLA) has been introduced under the trademark of Contramid® as a controlled release excipient for the preparation of solid dosage form.; Compaction properties were evaluated from the force-displacement profiles, Heckel plots and from the measure of crushing strength of the final tablets. The results demonstrated that CLA particles deform mainly by plastic flow during the compression process. The plasticity index and the yield pressure value are comparable to those of pregelatinized starch, and are independent of particle size, percentage of the fine particles and the presence of additives such as magnesium stearate (MgSt) and colloidal silicone dioxide (CSD). Water and CSD increase the compactibility of CLA, while MgSt has an opposite effect. Wet granulation increases the flowability and facilitates the consolidation of CLA powder. Presence of a binder such as hydroxypropylmethylcellulose (HPMC) leads to an increase in mechanical strength of the final compacts.; In water, CLA tablets swell and form a smooth, homogeneous and microporous hard gel layer. The equilibrium swelling reached, after incubation time of 6 h, a value of 200% (mass of water per mass of dry polymer) and is pH-independent. Mechanical studies on swollen matrices revealed that the CLA gel is 8-fold stronger than that of HPMC. The presence of HPMC into CLA matrices significantly reduces the gel strength, probably by altering the network formation of CLA.; Drug release in non-enzymatic medium occurs mainly by diffusion through the gel layer at a rate, which depends on their solubility in the medium. The presence of α-amylase in the dissolution medium results in the degradation of the CLA gel, and therefore increases the rate of the release.; Diffusion properties of small solutes through the CLA gel were evaluated using the diffusion cell method. The results clearly demonstrate that the diffusion coefficient (D_g) of drugs is greatly affected by their water solubility (S_w), and to a less extent, by their molecular weight (M_w). Molecules with high water solubility have a small partition coefficient (K), generally less than unity, and a high D _g value. (Abstract shortened by UMI.)