Polymethyl methacry late-antibiotic implants for the local treatment of osteomyelitis have been used in hospitals in the U.S. since the 1970s. This treatment requires a second surgery for removal of t he depleted implant. The purpose of this study is to investigate a new biodegradable implant system based upon poly(ortho esters) (POE) which can release tobramycin sulfate (TS) over a 21-day period (the usual clinical treatment period) with simultaneous and subsequent degradation of polymer in the tissues to harmless constituents. The POE-TS disks without any excipients showed a similar drug release pattern regardless of TS loading ( 4%, 8%, 12%, w/ w) and thickness (148, 244, 433 pm): 20%-60% TS-release within the first 24 hours followed by less than 10% release during the following 20 days with less than 3% weight loss of the polymer. These formulations did not meet therapeutic requirements of either drug release or polymer degradation rate. POE d egradation is known to be acid sensitive. To achieve uniform and high TS release over 21 days, various concentrations of lactic acid (LA), sorbic acid (SA), oleic acid (OA) and palmitoleic acids (PA) were incorporated in the 244pm-disks of 8% TS. The disks with LA demonstrated a pseudo zero-order TS release. With SA, OA & PA, the TS release was multi-phasic and the rate of polymer degradation was found to be acid concentration dependent. The TS release from these disks could be attributed to burst effect, polymer erosion and diffusion. Among these formulations, disks with 0.2% LA and 0 .9% OA gave the best release rate of 2mg TS/ day/ g implant; they achieved desirable therapeutic level of TS release and POE degradation. No physical or chemical interactio ns were detected by DSC, NMR and JR. Comparisons of POE weight loss and molecular weight loss with different acid catalysts revealed extremely different kinetics of acid catalysis. Uniform distribution of the drug in the disks was concluded based on content uniformity studies. Aqueous and solid state stability of TS were found to be suitable for clinical usage.

L’ostéomyélite chronique est une infection chronique du tissu osseux et de la moelle. C’est une infection grave du fait de sa localisation au sein d’un tissu profond, de la complexité de sa prise en charge thérapeutique et de la mise en jeu du pronostic fonctionnel. L’incidence de l’ostéomyélite chronique est accrue sur certains terrains (drépanocytose, diabète, et polyarthrite rhumatoïde entre autres). Son traitement classique repose sur un curettage chirurgical associé à une antibiothérapie par voie générale durant au moins 6 semaines. Ce traitement est marqué le plus souvent par des échecs du fait de la difficulté de faire parvenir des antibiotiques à doses efficaces et de manière prolongée ou continue au niveau de l'os infecté.<p>\ / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished