Sustained or controlled-release delivery systems can achieve predictable and reproducible release rates, extended duration of activity for short half-life drugs, decreased toxicity, reduction of required dose, optimized therapy, and better patient compliance. 1,2) With the aim of maximizing the bioavailability of conventional drugs with minimum side effects, new drug delivery systems continue to attract much attention.
3)Matrix-type controlled-delivery systems are popular because of their ease of manufacture. The simple preparation technique involves the compression of a blend of drug and polymer powder by conventional pharmaceutical methods to form disks or tablets. In inert matrix systems, which are also referred to as "monolithic" systems, the active agent is dissolved or dispersed in an inert diffusion barrier. The drug is mixed with an inert polymer that does not interact with biological fluids. Inert matrices should be insoluble and remain intact during the experiment. Drug release is controlled by the polymer properties and structure. [4][5][6][7] The materials used in the preparation of inert matrices are predominantly hydrophobic polymers. Several studies have dealt with the application of polymers such us polyvinylchloride, polyethylene, ethyl cellulose, acrylic resins, and polyamides. [8][9][10][11] Study of the toxicological, physicochemical, and pharmacotechnical properties of polyamide 12 have indicated that it is a nontoxic inert polymer with good characteristics for the production of tablets by the direct compression method. In previous reports we have confirmed slow drug release of compressed tablets with polyamide 12 in the composition.
12-15)The present study reports the use of polyamide 12 (Orgasol) as a new pharmaceutical vehicle in the design of solid controlled-release dosage forms. Inert polyamide 12 (empirical formula -NH-[CH 2 ] 11 -CO-) is obtained by polycondensation of aminolauric acid. Due to the hydrophobic and inert nature of Orgasol and its good fluidity and cohesion, 16) this polymer is a priori suitable for elaborate inert matrix systems. Metoclopramide hydrochloride was chosen as a model drug with high aqueous solubility, because of its pharmacokinetic properties of variable bioavailability (50%), short plasma half-life, and therapeutic interest. It is recommended for use as a potent antiemetic agent in various types of vomiting 17) (e.g., it is the antiemetic of choice for chemotherapyinduced emesis). Metoclopramide is a procainamide derivate with effects based on at least two mechanisms: first it acts in the central nervous system as an antagonist at D2 dopamine receptors; and second, metoclopramide has an agonistic effect on the cholinergic systems in the stomach and gut.18) The result is improved gastroduodenal coordination. High doses of metoclopramide inhibit the effects of serotonergic (5-HT 3 ) receptors on neurons in the gut, in addition to the effect of dopaminergic D 2 receptors at lower doses. Because the activity of metoclopramide is dose dependent, it is importan...