Rapid drug release

Recently, Tsakala et al. (90) formulated pyrimethamine systems based on several lactide/glycolide polymers. These studies were conducted with both microspheres (solvent evaporation process) and implants (melt extrusion process). In vitro studies indicated that pyrimethamine-loaded implants exhibited apparent zero-order release kinetics in aqueous buffer whereas the microspheres showed an initial high burst and considerably more rapid drug release. In vivo studies in berghi infected mice confirmed that the microspheres did not have adequate duration of release for practical application. However, the implants offer promise for future clinical work as more than 3 months protection was observed in animals. 

The effect of various chemical modifications on the mechanical properties of reconstituted collagen and the diffusion rates of the steroid medroxyprogesterone was investigated (38). Formaldehyde-treated films, which are heavily crosslinked, have high moduli and low rates of drug release. Films treated with chrome quickly become hydrated in solution and have low moduli and very rapid drug release characteristics. 

Starch is often cited as a filler, but it is more commonly used in its dry state as a disintegrating agent. However, modified starches such as StaRx 1500 and National 1551 (partially hydrolyzed, or pregelatinized starch) are marketed for direct compression and appear to offer the advantage of substantial mechanical strength and rapid drug release. 

The drug dosage form may also be affected by food. For example, enteric-coated tablets may stay in the stomach for a longer period of time because food delays stomach emptying. If the enteric-coated tablet does not reach the duodenum rapidly, drug release and subsequent systemic drug absorption are delayed. In contrast, enteric-coated beads or microparticles disperse in the stomach, are less affected by food, and demonstrate more consistent drug absorption from the duodenum. 

When a medicament is delivered orally, particularly when the dosage form is designed for rapid drug release, taste can be a substantial problem as many drugs have unpleasant flavors. Eliminating an unplea.sant flavor is essential to such dosage forms as poor patient compliance is expected when a dosage form is unpalatable. From a commercial perspective. an unpleasant flavor will result in reduced product sales as patients are likely to... 

Serum-stable formulations with minimal leakage at physiological pH and rapid drug release at pH 5.0-5.5 can be easily prepared by inserting a hydrophobicaUy modified iV isopropylacrylamide/ methacrylic acid copolymer (poly(NIPAM-co-MAA)) in the Hpid bilayer of sterically stabilized liposomes. The present chapter describes polymer synthesis, as well as the preparation, and characterization of large unilamelar pH-sensitive vesicles. 

Figure 11 Pulsatile drug-release patterns negligible release at early time points, followed by rapid and complete release after a predetermined lag phase. Exemplarily, a polymer-coated pellet is Ulustrated The intact macromolecular membrane effectively hinders drug release until the steadily increasing hydrostatic pressure within the pellet core (caused by the influx of water) induces crack formation, resulting in rapid drug release through water-filled pores/chaimels.

Strong positive charges to destroy liposomes for rapid drug release... 

F. Liu, et al, A novel concept in enteric coating A double-coating system providing rapid drug release in the proximal small intestine,/. Control. Release, 133 (2), 119-124, 2009. 

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