Microspheres polylactide

The use of polylactides for delivery of insect hormone analogs and other veterinary compounds (115,116) has been studied. Microspheres, pellets, and reservoir devices based on polyglycolide, poly-(DL-Iactide), poly(L-lactide), and various copolymers have been used to deliver methoprene and a number of juvenile hormone analogs. ... 

Figure 13.8. Effects of route and sustained release formulation on the time course of human growth hormone concentration in plasma. Shown is the average time course of human growth hormone (hGH) in plasma after intravenous (0.02mg/kg) and subcutaneous (0.1 mg/kg) administration in humans. Arrows indicate weekly subcutaneous dosing of hGH in solution. A single dose of the same protein formulated in polylactide-co-glycolide (PLG) microspheres (0.75 mg/kg) given subcutaneously sustains human growth hormone levels in plasma for at least one month.

Giunchedi P, Gavini E, Bonacucina G, Palmieri GF. Tabletted polylactide microspheres prepared by a w/o emulsion-spray drying method. J Microencapsul 2000 17(6) 711-720. 

Arshady, R. Preparation of biodegradable microspheres and microcapsules 2. Polylactides and related polyesters. J. Contr. Rel. 17 1—22, 1991. 

Keywords. Controlled drug delivery, Drug release, Microspheres, Degradation, Erosion, Polylactide, Poly(glycolide-co-lactide), Poly(e-caprolactone), Poly(hydroxyalkanoates) Polyanhydrides, Polycarbonates, Poly(orthoesters), Poly( l,5-dioxepan-2-one)... 

In the preparation of microspheres by solvent evaporation from oil-in-water emulsions, the presence of base (NaOH) was found to enhance the release of thioridazine from polylactide micro-spheres. The amount of drug release as a function of time was dependent on the amount of base added to the aqueous phase of the emulsion. Scanning electron micrographs indicate that this increased drug release may be due to modification of the internal structure of the microspheres by sodium hydroxide during fabrication. 

The present paper reports on a study which was conducted to investigate the effect of NaOH on the in vitro release profiles of microspheres prepared with polylactides (2) Since these polyesters degrade by hydrolysis (4), it is possible that the molecular weight of the polymers can be decreased by the alkaline pH of the sodium oleate emulsifier solution (pH 10) during fabrication. This in turn could affect the release kinetics of the microspheres. 

FONG ET AL. Enhancing Drug Release from Polylactide Microspheres... 

The second point is that the S-shapes of many of the release curves in this study indicate a biphasic pattern of drug release. This was also observed by Wakiyama et al (7-91. who used scanning electron microscopy to demonstrate that the second rise in the release rate was due to disintegration of the polylactide microspheres. 

The polylactides employed to form the matrices of these microspheres are known to be susceptible to alkaline hydrolysis. However, any alteration of the polymer by NaOH was not translated into any increase in drug release at the levels of base used in this investigation. 

Perugini, R, Genta, I., Pavanetto, F., Modena, T., Maculotti, K., and Conti, B. (2002), Evaluation of enzyme stability during preparation of polylactide-co-glycolide microspheres, J. Microencapsul., 19,591-602. 

However, in practice the glass transition is often superimposed by an endothermic response, as indicated in Figure 1.13 for a polylactide microsphere system (37) the change in the baseline before and after the event is clearly visible but, similarly, it is also clear that the potential for confusion with a melting endotherm is considerable. Furthermore, it is difficult to establish the exact position of the glass transition under such a peak with confidence, although methods are available whereby the Tg may be ascertained (20). 

FIGURE 1.13 DSC trace of glassy polylactide microspheres. (Reproduced from Passerini, N. and Craig, D.Q.M., J. Controlled Release 2001, 73, 111-115, 2001.)... 

Polymeric micropsheres, particularly those prepared from the biodegradable polylactide/ polyglycolide polymers, have been widely investigated as a means to achieve sustained parenteral drug delivery. The advantage of formulating the polymeric matrix as microspheres is the ability to administer them via a conventional needle and syringe as a suspension formulation, rather than as an implant (see below). Lupron depot formulations are available which can provide therapeutic blood levels of leuprolide acetate for up to four months. These products are presented as lyophilized polylactic acid microspheres which are reconstituted to form a suspension prior to administration. 

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