Influence of PLGA End Groups on the Release Profile of Dexamethasone from Ocular Implants

Abstract

The present study deals with the development of dexamethasone (DM)-loaded implants using ester end-capped Resomer RG 502 poly(lactic acid-co-glycolic acid) (PLGA) (502), acid endcapped Resomer RG 502H PLGA (502H), and a 502H:502 mixture (3:1) via hot melt extrusion (HME). The prepared intravitreal implants (20 and 40% DM loaded in each PLGA) were thoroughly investigated to determine the effect of different end-capped PLGA and drug loading on the long-term release profile of DM. The implants were characterized for solid-state active pharmaceutical ingredient (APIs) using DSC and SWAXS, water uptake during stability study, the crystal size of API in the implant matrix using hot-stage polarized light microscopy, and in vitro release profile. The kinetics of PLGA release was thoroughly investigated using quantitative 1 H NMR spectroscopy. The polymorph of DM crystal was found to remain unchanged after the extrusion and stability study. However, around 3 times reduction in API particle size was observed after the HME process. The morphology and content uniformity of the RT-stored samples were found to be comparable to the initial implant samples. Interestingly, the samples (mainly 502H) stored at 40 °C and 75% RH for 30 d demonstrated marked deformation and a change in content uniformity. The rate of DM release was higher in the case of 502H samples with a higher drug loading (40% w/w). Furthermore, a simple digital in vitro DM release profile derived for the formulation containing a 3:1 ratio of 502H and 502 was comparable with the experimental release profile of the respective polymer mixture formulation. The temporal development of pores and/or voids in the course of drug dissolution, evaluated using μCT, was found to be a precursor for the PLGA release. Overall, the release profile of DM was found to be dependent on the PLGA type (independent of subtle changes in the formulation mass and diameter). However, the extent of release was found to be dependent on DM loading. Thus, the present investigation led to a thorough understanding of the physicochemical properties of different end-capped PLGAs and the underlying formulation microstructure on the release profile of a crystalline water-insoluble drug, DM, from the PLGA-based implant.

Mechanistic Analysis of Temperature-Dependent Curcumin Release from Poly(lactic-co-glycolic acid)/Poly(lactic acid) Polymer Nanoparticles

“…It should be mentioned that the PLGA/PLA intrinsic polymers with a high L:G ratio and high molecular weight exhibited a small T g difference (Table ). Previous reports indicated that the PLGA/PLA polymers with a higher L:G ratio have a lower affinity with water due to the higher hydrophobicity of the lactic acid segment than that of the glycolic acid segment. − In addition, the PLGA/PLA polymer with low molecular weight becomes less hydrophobic, leading to more efficient water absorption. , The larger T g difference for the PLGA/PLA polymer with a low L:G ratio and low molecular weight could be explained by the higher plasticizing effect due to the greater affinity with water.…”

Gentamicin Eluting 3D-Printed Implants for Preventing Post-Surgical Infections in Bone Fractures

“…The PLGA-GEN showed an endothermic peak at 259.1 °C. This shift could be an indication of homogeneous dispersion of the drug in the PLGA matrix, and thus drug crystal could be coated with the PLGA-resomer …”

“…Gentamicin showed an endothermic peak at 123.8 °C followed by another endothermic peak at 244.8 °C, whereas PLGA showed a glass transition near 48 °C and remained stable until 330 °C without any sign of degradation, confirming results from previously published reports. 74,75 The PLGA-GEN layer showed a shift of the broad endothermic peak of the PLGA near the gentamicin endothermic peak. The PLGA-GEN showed an endothermic peak at 259.1 °C.…”

“…This shift could be an indication of homogeneous dispersion of the drug in the PLGA matrix, and thus drug crystal could be coated with the PLGA-resomer. 75 Another important aspect of an implantable device is its surface wettability, as it highly determines the cell growth's affinity-a hydrophilic surface is often desirable for cell differentiation and growth. A previously published report suggested that a selectively laser melted 316L SS using 3DP has improved wettability compared to a conventionally casted counterpart.…”

“…While assumptions are being made from the cross-section of coated area, it should not be ignored that the drug can leach out from the lower layers through the gaps between the layers and the rough-coated surfaces (as schematically depicted on Figure 4e), but it should be relatively smaller in comparison to the drug mediated toward release media through diffusion. The hydrophobic ester capping retards the penetration of water slower uptake, 75 which might be inadequate to flush gentamicin out of the matrix early. The PLGA layer is hydrophobic and does not erode early, which makes this release more diffusion mediated at this stage.…”