Time-oriented experimental design method to optimize hydrophilic matrix formulations with gelation kinetics and drug release profiles.
A new experimental design methodology was developed by integrating the response surface methodology and the time series modeling. The major purposes were to identify significant factors in determining swelling and release rate from matrix tablets and their relative factor levels for optimizing the experimental responses. Properties of tablet swelling and drug release were assessed with ten factors and two default factors, a hydrophilic model drug (terazosin) and magnesium stearate, and compared with target values. The selected input control factors were arranged in a mixture simplex lattice design with 21 experimental runs. The obtained optimal settings for gelation were PEO, LH-11, Syloid, and Pharmacoat with weight ratios of 215.33 (88.50%), 5.68 (2.33%), 19.27 (7.92%), and 3.04 (1.25%), respectively. The optimal settings for drug release were PEO and citric acid with weight ratios of 191.99 (78.91%) and 51.32 (21.09%), respectively. Based on the results of matrix swelling and drug release, the optimal solutions, target values, and validation experiment results over time were similar and showed consistent patterns with very small biases. The experimental design methodology could be a very promising experimental design method to obtain maximum information with limited time and resources. It could also be very useful in formulation studies by providing a systematic and reliable screening method to characterize significant factors in the sustained release matrix tablet.
Department of System Management & Engineering, Inje University, Gimhae 621-749, South Korea.
Sangmun
S
Shin
Du Hyung
du H
Choi
Nguyen Khoa Viet
NK
Truong
Nam Ah
NA
Kim
Kyung Rok
KR
Chu
Seong Hoon
SH
Jeong
D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry*; D005782:Gels; D015233:Models, Statistical; D011224:Prazosin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013229:Stearic Acids / Q000737:chemistry*; D013607:Tablets; D013997:Time Factors
D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; D013229:Stearic Acids; D013607:Tablets; C031183:stearic acid; C041226:Terazosin; D011224:Prazosin