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In the present study, a less known polyester based on tartaric acid was characterized with respect to its degradation mechanism. Poly(2,3-(1,4-diethyl tartrate)-co-2,3-isopropyliden tartrate) (PTA) differs from commonly used biodegradable polyesters, such as poly(lactides-co-glycolides) (PLGA) by the presence of additional cleavable bonds in the polymer side chains. This modification results in different polymer properties and influences polymer degradation. The hydrolytic degradation of PTA was studied in parallel to PLGA using disc-shape matrices, which were obtained by compression-molding. The discs were incubated in pH 7.4 phosphate buffer solution at 37 degrees C. The degraded samples were characterized for percentage mass loss, water absorption, decay of molecular weight and change in glass transition temperature. The results demonstrate that the degradation of PTA proceeds via bulk erosion similar to PLGA. However, the degradation of PTA implants is characterized by a rapid mass loss within a short period of time appearing after a definite lag phase without remarkable mass loss. This makes the polymer promising for pulsatile drug release systems.

Oligomers are thought to accelerate the hydrolytic degradation of devices prepared from poly(lactide-co-glycolide), PLGA, due to their increased number of carboxylic end groups. To experimentally verify this hypothesis, two D,L-lactic acid oligomers having molecular weights close to their critical limit of solubility were synthesized and incorporated into PLGA films in three concentrations (0, 10, and 30% w/w). All films were translucent, rather flexible and initially amorphous. With increasing oligomer concentration the glass transition temperature (T(g)) and the molecular weight of films decreased prior to erosion. The degradation studies show that initial mass loss and water absorption are increased in oligomer-containing films as a function of average molecular weight and oligomer concentration. However, the incorporation of oligomers does not accelerate the degradation of films. By contrast, oligomer-containing films show extended lag phase until onset of polymer erosion. This was shown to be related to crystallization. Moreover, it was found that crystallization occurs earlier in oligomer-containing films and that the degree of crystallization is related to the average molecular weight of the oligomer. These findings bring new insight into the role of oligomers in the degradation process and can be used to explain why erosion in massive polymer devices occurs from the center to the surface.

A series of low molecular weight polymers of d , l -lactic acid has been synthesized. The oligomers were characterized with respect to molecular weight, glass transition temperature and solubility. The number average molecular weight of the oligomers ranged from 290 to 1320 Da. Oligomers with an M n Da were soluble in buffer at pH 7.4 but insoluble in water and acidic medium. Kinetic studies were performed at pH 1.5, 4.5 and 7.4 using an accelerated in vitro monomer release test. The hydrolytic rate was dependent on molecular weight of oligomer, temperature and pH of the media, with the lowest rate found around pH 4.5. The activation energy was dependent on molecular weight and ranged from 47 to 67 kJ mol−1. Random ester cleavage was identified as mechanism of hydrolysis in basic media whereas in acidic media chain-end cleavage (“unzipping”) was the mode of action.

Here we investigated the possibility to develop different levels of correlation between in vitro drug release profiles and in vivo pharmacokinetic parameters for three Buserelin implant formulations. The in vitro and in vivo data were analyzed using model-independent and model-dependent methods. Since diffusion, dissolution and erosion effects influence drug release in most cases a simple kinetic model is unlikely to explain the overall in vivo release behavior. Thus the in vitro drug release curves were analyzed according to the theoretical models of Higuchi and Korsmeyer-Peppas. For the formulation with predominant diffusion controlled release level A IVIVC could be established (R2=0.986). Independent on drug release mechanism, a level B correlation between the mean in vitro dissolution time (MDT) and mean in vivo residence time (MRT) was obtained with a correlation coefficient of 0.983. Finally, level C correlation were observed when single in vitro parameters, e.g. T50% (time required to release 50% of drug in vitro) where compared with single in vivo parameters like AUC. This study suggests that a level B correlation could be achieved even when drug release occurs by a combination of diffusion and erosion processes. More sophisticated in vitro models mimicking drug release under in vivo conditions are clearly desirable for parenteral depot formulations.