TY - JOUR
T1 - Effects of porosity on drug release kinetics of swellable and erodible porous pharmaceutical solid dosage forms fabricated by hot melt droplet deposition 3D printing
AU - Zhang, Bin
AU - Nasereddin, Jehad
AU - McDonagh, Thomas
AU - von Zeppelin, Didier
AU - Gleadall, Andy
AU - Alqahtani, Fahad
AU - Bibb, Richard
AU - Belton, Peter
AU - Qi, Sheng
PY - 2021/7/15
Y1 - 2021/7/15
N2 - 3D printing has the unique ability to produce porous pharmaceutical solid dosage forms on-demand. Although using porosity to alter drug release kinetics has been proposed in the literature, the effects of porosity on the swellable and erodible porous solid dosage forms have not been explored. This study used a model formulation containing hypromellose acetate succinate (HPMCAS), polyethylene oxide (PEO) and paracetamol and a newly developed hot melt droplet deposition 3D printing method, Arburg plastic free-forming (APF), to examine the porosity effects on in vitro drug release. This is the first study reporting the use of APF on 3D printing porous pharmaceutical tablets. With the unique pellet feeding mechanism of APF, it is important to explore its potential applications in pharmaceutical additive manufacturing. The pores were created by altering the infill percentages (%) of the APF printing between 20 and 100% to generate porous tablets. The printing quality of these porous tablets was examined. The APF printed formulation swelled in pH 1.2 HCl and eroded in pH 6.8 PBS. During the dissolution at pH 1.2, the swelling of the printing pathway led to the gradual decreases in the open pore area and complete closure of pores for the tablets with high infills. In pH 6.8 buffer media, the direct correlation between drug release rate and infills was observed for the tablets printed with infill at and less than 60%. The results revealed that drug release kinetics were controlled by the complex interplay of the porosity and dynamic changes of the tablets caused by swelling and erosion. It also implied the potential impact of fluid hydrodynamics on the in vitro data collection and interpretation of porous solids.
AB - 3D printing has the unique ability to produce porous pharmaceutical solid dosage forms on-demand. Although using porosity to alter drug release kinetics has been proposed in the literature, the effects of porosity on the swellable and erodible porous solid dosage forms have not been explored. This study used a model formulation containing hypromellose acetate succinate (HPMCAS), polyethylene oxide (PEO) and paracetamol and a newly developed hot melt droplet deposition 3D printing method, Arburg plastic free-forming (APF), to examine the porosity effects on in vitro drug release. This is the first study reporting the use of APF on 3D printing porous pharmaceutical tablets. With the unique pellet feeding mechanism of APF, it is important to explore its potential applications in pharmaceutical additive manufacturing. The pores were created by altering the infill percentages (%) of the APF printing between 20 and 100% to generate porous tablets. The printing quality of these porous tablets was examined. The APF printed formulation swelled in pH 1.2 HCl and eroded in pH 6.8 PBS. During the dissolution at pH 1.2, the swelling of the printing pathway led to the gradual decreases in the open pore area and complete closure of pores for the tablets with high infills. In pH 6.8 buffer media, the direct correlation between drug release rate and infills was observed for the tablets printed with infill at and less than 60%. The results revealed that drug release kinetics were controlled by the complex interplay of the porosity and dynamic changes of the tablets caused by swelling and erosion. It also implied the potential impact of fluid hydrodynamics on the in vitro data collection and interpretation of porous solids.
KW - Arburg plastic free-forming
KW - Controlled drug release
KW - Hot melt droplet deposition 3D printing
KW - Hot melt extrusion
KW - Infill control
KW - Porous solids
UR - http://www.scopus.com/inward/record.url?scp=85105310684&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2021.120626
DO - 10.1016/j.ijpharm.2021.120626
M3 - Article
VL - 604
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 120626
ER -