{'fraction_non_alphanumeric': 0.03490909090909091, 'fraction_numerical': 0.014545454545454545, 'mean_word_length': 4.905579399141631, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
D-Optimal Mixture Design: Optimization of Ternary Matrix Blends for Controlled Zero-Order Drug Release From Oral Dosage Forms

ABSTRACT The objective of the present study was to develop a tablet formulation with a zero-order drug release profile based on a balanced blend of three matrix ingredients. To accomplish this goal, a 17-run, three-factor, two-level D-Optimal mixture design was employed to evaluate the effect of Polyox™ (X1), Carbopol® (X2), and lactose (X3) concentrations on the release rate of theophylline from the matrices. Tablets were prepared by direct compression and were subjected to an in vitro dissolution study in phosphate buffer at pH 7.2. Polynomial models were generated for the responses Y4 (percent released in 8 h) and Y6 (similarity factor or f2). Fitted models were used to predict the composition of a formulation that would have a similar dissolution profile to an ideal zero-order release at a rate of 8.33% per hour. When tested, dissolution profile of the optimized formulation was comparable to the reference profile (f2 was 74.2, and n [release exponent] was 0.9). This study demonstrated that a balanced blend of matrix ingredients could be used to attain a zero-order release profile. Optimization was feasible by the application of response surface methodology, which proved efficient in designing controlled-release dosage forms.