Drug release kinetics

Recently, Brich and coworkers (40) reported the synthesis of lactide/glycolide polymers branched with different polyols. Polyvinyl-alcohol and dextran acetate were used to afford polymers exhibiting degradation profiles significantly different from that of linear poly-lactides. The biphasic release profile often observed with the linear polyesters was smoothened somewhat to a monophasic profile. Further, the overall degradation rate is accelerated. It was speculated that these polymers can potentially afford more uniform drug release kinetics. This potential has not yet been fully demonstrated. 

Because of the extreme differences between conventional pharmaceuticals and the protein molecules in terms of formulation techniques and drug release kinetics, the two categories will be discussed separately here. 

Extensive studies have been reported with cisplatin in the field of chemoembolization (59,98). Microspheres prepared by a solvent evaporation procedure were characterized in vitro and critical processing parameters in regard to drug release kinetics were identified. 

Xu et al. (2001) synthesized the copolymers of a dimer fatty acid (dimer of oleic and linoleic acids) and sebacic acid (P(DA-SA)) by melt polycondensation of acetylated prepolymers. Degradation and drug release kinetics showed that increasing dimer acid content decreased the release rate (Xu et al., 2001). 

In vitro Degradation, Erosion, and Drug Release Kinetics... 

Whether in copolymers or blends, inhomogeneous erosion has a nontrivial effect on drug release kinetics as will be shown later. Leong et al. (1985) demonstrated that the pH of the degradation media also has a dramatic effect on the erosion rate, which increases with increasing pH. The acceleration of degradation of polyanhydrides with increase in pH is widely reported and has been used to speed up experiments (Shakesheff et al., 1994). 

The past two decades have produced a revival of interest in the synthesis of polyanhydrides for biomedical applications. These materials offer a unique combination of properties that includes hydrolytically labile backbone, hydrophobic bulk, and very flexible chemistry that can be combined with other functional groups to develop polymers with novel physical and chemical properties. This combination of properties leads to erosion kinetics that is primarily surface eroding and offers the potential to stabilize macromolecular drugs and extend release profiles from days to years. The microstructural characteristics and inhomogeneities of multi-component systems offer an additional dimension of drug release kinetics that can be exploited to tailor drug release profiles. 

P.Catellani, G.Vaona, P.Plazzi and P.Colombo, Compressed matrices formulation and drug release kinetics, Acta Pharm. Technol., 34 (1), 38-41 (1988). 

The present study was undertaken to investigate the effect of physicochemical properties of wall-forming materials on the drug release kinetics and bioavailability of microcapsules and micromatrices. The effect of a coacervation-inducing agent on the drug release profile was also studied. 

J. L. Ford, M. H. Rubinstein, F. McCaul, et al. Importance of drug type, tablet shape and added diluents on drug release kinetics from hydroxypropymethylcellulose matrix tablets. Int. J. Pharm. 40 223-234, 1987. 

J. Siepmann, K. Podual, M. Sriwongjanya, et al. Anew model describing the swelling and drug release kinetics from hydroxypropyl methylcellulose tablets. J. Pharm. Sci. 88 65-72, 1999. 

See color plate) Atomic force microscopy images and drug release kinetics of the paclitaxel-poly(styrene-i>isobutylene-i>styrene) polymer combination. Abbreviations PTx, paclitaxel SIBS, poly(styrene-b-isobutylene-b-slyrene). 

Overall, key takeaways from the nonpoly meric paclitaxel delivery studies were that despite their improvement of angiographic parameters, paclitaxel-eluting stents without a polymer carrier did not demonstrate a positive effect on clinical outcomes, as seen with polymer-based paclitaxel elution (65), discussed in the next section. Potential reasons for the failure of such an approach could be loss of drug to the systemic circulation prior to reaching the target site during the stent deployment procedure, variability associated with the dose delivered to the lesion, and lack of control over drug-release kinetics due to the absence of a polymer carrier. 

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