ethyl-cellulose and fumaric-acid

The aim was to design a pH-sensitive pulsatile drug delivery system that allows for an on-off pulsed release of a drug using polyacrylic acid (PAA) blended with ethyl cellulose (EC) in different ratios. PAA, a polyelectrolyte polymer, exhibits a highly coiled conformation at low pH but a highly extended structure at high pH. Fumaric acid, which is an internal acidifying agent, was incorporated into the hydroxypropyl methylcellulose-based core tablets to create an acidic microenvironmental pH (pH(M)). The concentration of fumaric acid inside the core tablet and the ratio of PAA/EC in the coating layer were very crucial in modulating drug release behaviors. When the fumaric acid was retained in the core tablet, it gave a more acidic pH(M), so that the PAA was kept in a highly coiled state in the coated film, which hindered drug release ("off" release pattern). Interestingly, the release profiles of the drug and fumaric acid from coated tablets showed the on-off pulsed pattern upon dissolution. Imaging analyses using scanning electron microscopy, near-infrared imaging, confocal laser scanning microscopy, and Fourier transform infrared spectroscopy confirmed this on-off release behavior of the drug and fumaric acid from coated tablets.

Topics: Acrylic Resins; Bronchodilator Agents; Cellulose; Delayed-Action Preparations; Drug Compounding; Excipients; Fumarates; Hydrogen-Ion Concentration; Hypromellose Derivatives; Methylcellulose; Microscopy, Confocal; Polymers; Solubility; Spectroscopy, Fourier Transform Infrared; Spectroscopy, Near-Infrared; Tablets; Terbutaline

The objective of this study was to develop a rupturable, capsule-based pulsatile drug delivery system with pH-independent properties prepared using aqueous coating. The drug release is induced by rupturing of the top-coating, resulting by expanding of swellable layer upon water penetration through the top-coating. Croscarmellose sodium (AcDiSol) is a preferable superdisintegrant compared to low substituted hydroxypropylcellulose (L-HPC) and sodium starch glycolate (Explotab), because of controlled lag time, followed by a quick and complete drug release. However, due to its anionic character, AcDiSol showed pH-dependent swelling characteristics (pH 7.4 > 0.1N HCl) resulting in a pH-dependent lag time. The pH dependency could be eliminated by the addition of fumaric acid to the swelling layer, which allowed to keep an acidic micro-environment. Formation of the rupturable top-coating was successfully performed using an aqueous dispersion of ethylcellulose (Aquacoat) ECD), whereby sufficient drying during the coating was needed to avoid swelling of the AcDiSol layer. A higher coating level was required, when aqueous dispersion was used, compared to organic coatings. However, an advantageous aspect of the aqueous coating was the lower sensitivity of the lag time to a deviation in the coating level.

Topics: Capsules; Cellulose; Desiccation; Drug Compounding; Drug Delivery Systems; Drug Stability; Fumarates; Gelatin; Humidity; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Pulsatile Flow; Solubility; Surface Properties; Water