Microencapsulation is an effective strategy to deliver drugs and actives locally or provide control on drug release over a long period of time. Nevertheless, a number of problems require careful management of microencapsulation procedures. Drug loading related plasticization of microparticles (MP) can affect formulation stability and recovery [1]. In this work, we investigated issues related to the plasticizing effect of 4-methoxy chalcone (4-MC) [2] upon encapsulation in polylactide (PLA) and poly(lactide-co.glycolide) (PLGA) polymers. RG202S, RG202H, RG504H, RG504, RG502, PDLG5004A 50/50, and PDLG7507 (75:25) polymers were employed. 4-MC was loaded at 5%, 10% and 20% w/w by a solvent evaporation method [3]. The MP were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), particle size and in vitro drug release analysis. 4-MC caused a loading-dependent change in MP structure and morphology and, for RG202S, MP recovery was impaired. A loading–dependent shift from anti-plasticizing to plasticizing effect was observed, especially for higher MW polymers. 4-MC was generally amorphous in the MP with some crystallinity only at 20% w/w loading in lower MW polymers. In vitro drug release was affected by polymer plasticization and it was slower with non-endcapped polymers, such as RG504, R202H, PDLG5004A and PDLG7507. In order to prevent such issues, inclusion of 4-MC in stearate-Zn-Al hydrotalcites (sHTC) was selected as a potential strategy. 4-MC was intercalated in sHTC up to a 30-50% w/w and thereafter microencapsulated by a W/O/W solvent evaporation method in the same conditions previously employed. The use of sHTC reduced or completely suppressed the plasticizing effect of 4-MC on R202S MP allowing recovery of MP with good morphological features and slower drug release as a result of a harder polymer matrix. On the other hand, at 20% loading, release was higher with sHTC due to a higher 4-MC-sHTC presence on the MP surface and solubility enhancement. In conclusion, non-endcapped higher MW polymers provided the best MP features even at high 4-MC loading. However, the use of sHTC ensures better MP performances and potential storage stability and it could be proposed as a preventive strategy for the encapsulation of strong plasticizing drugs.
MICROENCAPSULATION ISSUES IN BIODEGRADABLE POLIMERIC MICROPARTICLES: THE CASE OF 4-METHOXY CHALCONE
M. Puccetti
;S. Giovagnoli;R. Vivani;M. Ricci
2017
Abstract
Microencapsulation is an effective strategy to deliver drugs and actives locally or provide control on drug release over a long period of time. Nevertheless, a number of problems require careful management of microencapsulation procedures. Drug loading related plasticization of microparticles (MP) can affect formulation stability and recovery [1]. In this work, we investigated issues related to the plasticizing effect of 4-methoxy chalcone (4-MC) [2] upon encapsulation in polylactide (PLA) and poly(lactide-co.glycolide) (PLGA) polymers. RG202S, RG202H, RG504H, RG504, RG502, PDLG5004A 50/50, and PDLG7507 (75:25) polymers were employed. 4-MC was loaded at 5%, 10% and 20% w/w by a solvent evaporation method [3]. The MP were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), particle size and in vitro drug release analysis. 4-MC caused a loading-dependent change in MP structure and morphology and, for RG202S, MP recovery was impaired. A loading–dependent shift from anti-plasticizing to plasticizing effect was observed, especially for higher MW polymers. 4-MC was generally amorphous in the MP with some crystallinity only at 20% w/w loading in lower MW polymers. In vitro drug release was affected by polymer plasticization and it was slower with non-endcapped polymers, such as RG504, R202H, PDLG5004A and PDLG7507. In order to prevent such issues, inclusion of 4-MC in stearate-Zn-Al hydrotalcites (sHTC) was selected as a potential strategy. 4-MC was intercalated in sHTC up to a 30-50% w/w and thereafter microencapsulated by a W/O/W solvent evaporation method in the same conditions previously employed. The use of sHTC reduced or completely suppressed the plasticizing effect of 4-MC on R202S MP allowing recovery of MP with good morphological features and slower drug release as a result of a harder polymer matrix. On the other hand, at 20% loading, release was higher with sHTC due to a higher 4-MC-sHTC presence on the MP surface and solubility enhancement. In conclusion, non-endcapped higher MW polymers provided the best MP features even at high 4-MC loading. However, the use of sHTC ensures better MP performances and potential storage stability and it could be proposed as a preventive strategy for the encapsulation of strong plasticizing drugs.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
