For the last two decades, mixtures of D‐ and L‐lactides, the DD and LL cyclic dimers of lactic acid enantiomers, were polymerized under various conditions of temperature, time, and initiators. Consequences of the dimeric structure of lactide molecules on the distribution of chiral units and on the properties of resulting PLAs were discussed occasionally. In the meantime, NMR techniques have grown up and are now powerful tools to investigate configurational structures from stereosensitive resonances. Thus far, correlation between experimental data and theoretical n‐ades were based on Bernoullian‐type enchainments of DD and LL pairs of lactyl units present in PLA stereocopolymer chains obtained by ring‐opening polymerization. Analysis of NMR spectra of racemic PLAs of different origins, including literature data, was reconsidered on the basis of the probabilities to form iso‐ and hetero‐dyads during chain propagation. Consideration of equireactivity and stereodependent reactivity between the DD and LL pairs generated from a racemic mixture of D‐ and L‐lactide diastereoisomers led us to the conclusion that DD/LL and LL/DD heterotactic junctions are preferentially formed when one uses Sn octoate and Zn metal as initiator systems, even though completed macromolecules remain predominantly isotactic because of the isodyads inherently present in lactide diastereoisomers. A simple method is proposed to determine whether homo‐ or cross‐addition of DD and LL pairs is favorized in any poly(racemic lactide) in the absence of transesterification rearrangements. This method is based on the comparison of experimental relative weights of the three distinct groups of resonances due to carbonyl carbon atoms with relative weights calculated according to the Bernoullian statistics. It allows the determination of a coefficient of stereoselectivity Pi from which one can easily evaluate the average length of isotactic blocks Li without any computation approximations. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 1651–1658, 1997

In the field of controlled drug delivery, most of the reported work is aimed at introducing new systems, or at providing basic information on the critical parameters which affect release profiles in vitro and occasionally in vivo. The situation is totally different when one wants to fulfil the specific requirements imposed by the marketing of a sustained release device to be used in humans or in animals eaten by human beings. The control of the release characteristics is then a difficult challenge. In this work, attempts were made to combine cephradin, a hydrophilic beta-lactam antibiotic, and bioresorbable polymeric matrices of a poly(alpha-hydroxy acid) in the form of microspheres with the aim of delivering the antibiotic to cattle at a dose rate of 4-5 mg/kg/day over a 3-4 days period after i.m. injection. PLAGA aliphatic polyesters were selected because they are already FDA approved as matrices. The solvent evaporation technique using PVA as the emulsion stabilizer was selected because it is efficient and can be extended to an industrial scale. Various experimental conditions were used in order to obtain the highest encapsulation yields compatible with the desired specifications. Decreasing the volume of the aqueous phase and adding a water-miscible organic solvent/non-solvent of cephradin failed. In contrast, microspheres containing up to 30% cephradin were prepared after addition of sodium chloride to the aqueous dispersing phase. The amount of entrapped drug was raised to 40% by decreasing the temperature and the pressure. Preliminary investigations using dogs showed that 20% cephradin microspheres prepared under these conditions extended the presence of cephradin in the blood circulation up to 48 h. Increasing the load led to higher blood concentrations but shorter sustained release. The fact that the microspheres were for cattle limited the volume of the injection and thus the amount of microspheres to be administered. The other limiting factors were related to microsphere morphology.