In-situ forming PLGA implants: How additives affect swelling and drug release

Abstract The aim of this study was to investigate the impact of the addition of very different types of additives on the key features of in-situ forming implants based on poly(D,L-lactic-co-glycolic acid) (PLGA, Resomer RG 502H) loaded with dexamethasone. All ingredients were dissolved in N-methyl-pyrrolidone (NMP), the implants formed upon solvent exchange. Crosslinked poly(acrylic acid) (Carbopol), poly(ethylene glycol) (PEG 400), hydroxypropyl methylcellulose (HPMC K100, HPMC E15), stearic acid and acetyltributyl citrate (ATBC) were studied as additives, in concentrations up to 5% (except for ATBC: up to 20%). Dynamic changes in the implants' wet mass, pH of the release medium, NMP leaching as well as dexamethasone release were monitored upon exposure to phosphate buffer pH 7.4. Also the implants’ inner and outer morphology was studied, using optical and scanning electron microscopy. Interestingly, the addition of the very different types of additives partially substantially altered the morphology and swelling kinetics of the investigated in-situ forming PLGA implants, whereas the impact on dexamethasone release was rather limited in all cases. Generally, the release rate slightly increased in the presence of the additives, only in the case of ATBC it slightly decreased. The overall limited effect on drug release might at least partially be attributed to the fact that: (i) water-soluble additives might rapidly leach out into the aqueous release medium during implant formation and/or promote implant swelling, and (ii) lipophilic additives might induce phase separation.