TY - JOUR
T1 - Formulation optimization and in vitro characterization of orally disintegrating films using a factorial design and mathematical modeling for drug release
AU - Lee, Yeongbin
AU - Thapa, Prakash
AU - Jeong, Seong Hoon
AU - Woo, Mi Hee
AU - Choi, Du Hyung
N1 - Publisher Copyright:
© 2017 The Pharmaceutical Society of Japan.
PY - 2017
Y1 - 2017
N2 - Even though experimental designs are becoming popular especially for conventional dosage forms, limited studies have been performed to optimize formulations of orally disintegrating films (ODFs). This study aimed to evaluate sildenafil citrate-loaded ODFs for a controlled release with hydroxypropyl methylcellulose as a film-forming polymer. A factorial design was utilized for optimization with three control factors: ethanol ratio, plasticizer ratio, and the type of plasticizer. Tensile strength, disintegration time, water contact angle, and thickness were chosen as responses. For optimization, water contact angle, disintegration time, and thickness were minimized, while the tensile strength was maximized. Based on the conditions, optimal formulations were achieved for each type of plasticizer. Evaluation of desirability indicated that the response values were close to the target. When these optimal formulations were validated, the optimal solutions and target values were similar with small biases. The formulations were characterized using scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, surface pH, in vitro dissolution, and drug release simulation with a mathematical modeling. After the drug was homogenously dispersed throughout the film, the crystalline form of the drug provided strong hydrogen bonds between the drug and the film components. Moreover, it showed a controlled drug release profiles that were well matched with simulated results. This study suggests that the optimized films may present a better alternative to conventional tablets for the treatment of male erectile dysfunction.
AB - Even though experimental designs are becoming popular especially for conventional dosage forms, limited studies have been performed to optimize formulations of orally disintegrating films (ODFs). This study aimed to evaluate sildenafil citrate-loaded ODFs for a controlled release with hydroxypropyl methylcellulose as a film-forming polymer. A factorial design was utilized for optimization with three control factors: ethanol ratio, plasticizer ratio, and the type of plasticizer. Tensile strength, disintegration time, water contact angle, and thickness were chosen as responses. For optimization, water contact angle, disintegration time, and thickness were minimized, while the tensile strength was maximized. Based on the conditions, optimal formulations were achieved for each type of plasticizer. Evaluation of desirability indicated that the response values were close to the target. When these optimal formulations were validated, the optimal solutions and target values were similar with small biases. The formulations were characterized using scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, surface pH, in vitro dissolution, and drug release simulation with a mathematical modeling. After the drug was homogenously dispersed throughout the film, the crystalline form of the drug provided strong hydrogen bonds between the drug and the film components. Moreover, it showed a controlled drug release profiles that were well matched with simulated results. This study suggests that the optimized films may present a better alternative to conventional tablets for the treatment of male erectile dysfunction.
KW - Controlled release
KW - Factorial design
KW - Hydroxypropyl methylcellulose
KW - Mathematical modeling
KW - Optimization
KW - Orally disintegrating film
UR - http://www.scopus.com/inward/record.url?scp=85011000634&partnerID=8YFLogxK
U2 - 10.1248/cpb.c16-00757
DO - 10.1248/cpb.c16-00757
M3 - Article
C2 - 27904030
AN - SCOPUS:85011000634
SN - 0009-2363
VL - 65
SP - 166
EP - 177
JO - Chemical and Pharmaceutical Bulletin
JF - Chemical and Pharmaceutical Bulletin
IS - 2
ER -