Burst release

Nanotechnology has led to very efficient versions of liposomes. Tiny hollow spheres only nanometers in diameter hold even tinier capsules of medicine. The spheres are made of silica covered with gold nanoparticles and when they are coated with antibodies they attach to tumor cells. The spheres are sensitive to light of specific wavelengths and when the light is applied, either heat up and destroy the tumor, or burst, releasing the drugs within the capsules directly into the tumor. 

Kesler, D. J., Cruz, L. C., McKenzie, J. A., and Henderson, E. A., The effect of GNRH burst release on the efficacy of GnRH microcapsules, Proc. Int. Control. Rel. Bioact. Mater.,... 

Drug release profiles from the tablets in various dissolution media are shown in Fig. 2. In all cases the release rates decreased initially from the control (distilled water) as electrolyte concentration increased, until a minimum release rate was obtained. As the electrolyte concentration further increased the release rates similarly increased until a burst release occurred. These initial decreases in release rates were probably coincident with a decrease in polymer solubility, in that as the ionic strength of the dissolution medium is increased the cloud point is lowered towards 37°C. It may be seen from Table 5 that minimum release rates occurred when the cloud point was 37°C. At this point the pore tortuosity within the matrix structure should also be at a maximum. It is unlikely to be an increase in viscosity that retards release rates since Ford et al. [1] showed that viscosity has little effect on release rates. Any reduction in hydration, such as that by increasing the concentration of solute in the dissolution media or increasing the temperature of the dissolution media, will start to prevent gelation and therefore the tablet will cease to act as a sustained release matrix. 

Fig. 7.2. Diagram of the PDS-1000/He, a stationary particle bombardment machine that is connected to a helium gas container. Controlled by adjustable valves, the gas stream (He) terminates in an acceleration tube, which is mounted on the top of a target chamber. This chamber is closed by a door and set under vacuum shortly before bombardment. When gas flows into the acceleration tube, the rupture disc bursts releasing the shock wave into the lower part of the tube. The gas pressure then accelerates the macrocarrier sheet containing the microprojectiles on its lower surface. The net-like stopping screen holds the macrocarrier sheet back and serves to block the shock wave, while the microprojectiles slip through the pores of the grid and continue on towards their final target.

Soo et al. (2002) studied tliB vitro release of hydrophobic Luorescent probes from PEO-b PCL micelles. Micelle solutions were placed in dialysis bags (MWCO 50,000) in a stirred water bath with a constant overLow of distilled water. This maintained the release environment at near perfect sink conditions, so the limited solubility ofthe probes in the medium did not affect release kinetics. Release was determined by removing aliquots ofthe dialysis bag contents and measuring Luorescently. Soo et al. found an initial burst release of probe followed by slow diffusional release. For the probes studies, benzopyrene and Cell-Tracker-CM-Dil, diffusion constants were ofthe order 10"15 cnnP/s. 

This occurred because of the rapid phase transition and slower evaporation and formation of nonporous microspheres in presence of ethyl-acetate. DCM produced porous microspheres and hence showed initial burst release. Use of ethanol along with DCM further increased the initial burst because of the structure of microspheres and inhomogeneous drug distribution. This feature may be very useful during the design of sustained release particulate carriers for highly water-soluble drugs. 

The sodium naproxen extended release formulation from Andrx Pharmaceuticals contains a portion of the drug for initial burst release and another portion in the form of a sustained release matrix. Plasma levels of the drug are detected within 30 minutes of dosing, with peak plasma levels occurring at about 5 hours after dosing. 

A sustained drug release is favourable for drugs with short elimination half-life. It can be controlled by hydration and diffusion mechanisms or ionic interactions between the drug and the polymeric carrier. In the case of diffusion control the stability of the carrier system is essential, as its disintegration leads to a burst release. Therefore, the cohesiveness of the polymer network plays a crucial role in order to control the release over several hours. Due to the formation of disulphide bonds within the network thiomers offer adequate cohesive stability. Almost zero-order release kinetics could be shown for insulin embedded in thiolated polycarbophil matrices (Clausen and Bernkop-Schnurch 2001). In the case of peptide and protein drugs release can be controlled via ionic interactions. An anionic or cationic polymer has to be chosen depending... 

An initial burst release of leuprolide from the microsphere depot occurs in vivo, followed by quasi-linear release for the rest of the time period. The efficacy of leuprolide depot formulations was found to be the same as the efficacy achieved with daily subcutaneous injections of 1 mg leuprolide formulation. 

In the other procedure, Rojas et al. [215] optimized the encapsulation of BLG within PLGA microparticles prepared by the multiple emulsion solvent evaporation method. The role of the pH of the external phase and the introduction of the surfactant tween 20, in the modulation of the entrapment and release of BLG from microparticles were studied. Better encapsulation of BLG was noticed on decreasing the pH of the external phase. Addition of tween 20 increased the encapsulation efficiency of BLG and considerably reduced the burst release effect. 

PH Acidic or basic hydrogel Change in pH, swelling-diffusion, erosion or burst release of drug... 

Wang, J., Wang, B. M., and Schwendeman, S. P. (2004), Mechanistic evaluation of the glucose-induced reduction in initial burst release of octreotide acetate from poly(D,L-lactide-co-glycolide) microspheres, Biomaterials, 25,1919-1927. 

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