Poly(l-lactide-со-glycolide) and shellac in the development of phase-sensitive in situ implants

Aim to consider the potential prospects of using Poly(l-lactide-co-glycolide) (PLGA) and shellac to obtain phase-dependent in situ implants. 
Material and methods. The study required two stages: stage I was the evaluation of NMP-polymer compositions, and stage II was the evaluation of NMP-polymer-PEG compositions. We used PLGA with various ratios of lactide and glycolide units (75:25, 50:50), dewaxed bleached shellac, N-methylpyrrolidone (NMP) as a solvent, and PEG-1500 at a concentration of 5% (wt/vol) as a co-solvent. The experimental formulations contained matrix formers at a concentration of 33%. The formulations were screened for polymer solubility in NMP, homogeneity and permeability through the needle of the resulting polymer-NMP system, the implant formation rate during the liquid-liquid extraction in a phosphate buffer solution (pH=6.8), and the implant morphology. The rate of implant formation and the diffusion of the dye from the delivery systems were also studied using the in vitro agar gingiva model, previously developed in the laboratory of the A.P. Nelyubin Institute of Pharmacy. 
Results. The first stage of the study showed that the NMP-PLGA system (75:25) formed a solid implant in 1 hour, and the NMP-shellac system in 2 hours. The formulations were positively assessed according to the presented criteria, despite the very different diffusion volumes 1414 l for NMP-shellac and 1065 l for NMP-PLGA (75:25) which indicates the possibility of their use without the introduction of additional excipients. The NMP-PLGA system (50:50) had not completely precipitated after the critical time (3 hours) and was considered as requiring an adjustment due to the insufficient implant formation rate. 
In the stage II, a less intense diffusion of the dye from the implants into agar was observed. For example, for NMP-PLGA(50:50) 641 l, and for NMP-PLGA(50:50)-PEG 25 l. At the same time, there was the positive dynamics in the time of their precipitation both in phosphate buffer medium (instantaneous precipitation without the need for shaking) and in the in vitro agar gingiva model after 3 hours, the composition of NMP-PLGA (50:50)-PEG, in contrast to NMP-PLGA (50:50), had formed a semi-solid implant. 
Conclusion. In the course of the experiments, the compositions of NMP-shellac and NMP-PLGA (75:25) were selected as the most promising for further development of a phase-sensitive in situ dental implant. The addition of PEG was found to be rational in terms of increasing the rate of implant precipitation and reducing the initial diffusion of the solvent.