Enteric-Coated Drug-Pillared Layered Double Hydroxides As A Controlled Release Drug Delivery System

Layered double hydroxides (LDHs), or so-called anionic clays, consist of cationic brucite-like layers and exchangeable interlayer anions. Because of their biocompatibility, these layered inorganic solids can be used as host materials to create drug-LDH host-guest supramolecular structures. The interlayer anion exchangeable capability of LDHs meets the requirement of inorganic matrices for encapsulating functional drugs with negative charge in aqueous media. The anti-inflammatory drug fenbufen,diflunisal and ibuprofen have been intercalated into layered double hydroxides for the first time by co-precipitation under a nitrogen atmosphere. The products have been characterized by powder X-ray diffraction (XRD), and show an expanded LDH structure, indicating that the drug have been successfully intercalated into LDH. In addition, the dependence of the nature of the fenbufen intercalation process on conditions such as pH value temperature, molar ratio, reaction time and chemical composition of the host have been systematically investigated. The interlayer distance in the intercalated materials increases with increasing pH value, resulting from a change in the arrangement of interlayer anions from monolayer to bilayer. Drug release characteristics of the pillared LDH materials were investigated by a dissolution test in a simulated intestinal fluid (buffer at pH 7.8). The results show that the drug release of supramolecular LDH materials was a slow process, especially in the case of Mg-Al intercalated materials, suggesting that these drug-inorganic hybrid materials can be used as an effective drug delivery system.LDHs are basic compounds however, and will dissolve rapidly in gastric acid, with complete liberation of the intercalated drug in the stomach. This means the use of LDHs as drug delivery system will be limited because of complete liberation of the intercalated drug in the stomach.In this paper, we have shown that intercalation of fenbufen in a layered double hydroxide followed by coating with enteric gives a composite material which shows controlled release of the drug under in vitro conditions which model the passage of a material through the gastrointestinal tract. As the enteric coating we select Eudragit? L 100 and S 100, which have been widely used in this area. Those anionic copolymers of methacrylic acid and methyl methacrylate have a molecular weight of approximately 135,000 with a ratio of acid to ester of approximately 1:1 in Eudragit? L 100 and 1:2 in Eudragit? S 100. Both polymers are insoluble in aqueous acid solution but Eudragit? L 100 dissolves at pH 6 and above and Eudragit? L 100 at pH 7 and above. Work is underway in our laboratory to explore how the drug release characteristics may be modified by variation of the physicochemical properties of both the layered double hydroxide and the polymer coating.