Interpolymer complexation between copovidone and carbopol and its effect on drug release from matrix tablets

Abstract

The interaction between copovidone and Carbopol 907 is pH dependent. When the pH of an aqueous solution fell below pH 4.5, a water-insoluble complex began to form and precipitate. This complex resulted from a hydrogen-bond-induced interaction between the carboxylic groups in Carbopol 907 and the carbonyl groups of N-vinylpyrrolidone repeat units in copovidone. Consisting of these two polymers at an approximate 1:1 weight ratio, the complex was an amorphous material with a glass transition temperature of 157 °C. The interpolymer complexation in situ was applied to modify drug release properties of Carbopol 907-based theophylline matrix tablets. The effect of copovidone on drug release was dependent on the pH of the dissolution medium. In a 0.1 N hydrochloride acid solution at pH 1.2 and 50 mM acetate buffer at pH 4.0, an insoluble tablet matrix was formed as a result of the in situ interpolymer complexation, and theophylline was released therefore via Fickian diffusion. In a 50 mM phosphate buffer at pH 6.8, drug release from the matrix tablets was still impacted by the in situ interpolymer complexation because of the low-pH microenvironment induced by Carbopol 907. As a result, drug release rate of the matrix tablet containing both polymers at pH 6.8 was slower than that of the matrix tablets containing individual polymers. We observed similar drug release rates at both pH 1.2 and pH 6.8 between tablets containing the physical blend of these two polymers and tablets containing preformed interpolymer complexes.

Disparities of Single-Particle Growth Rates in Buried Versus Exposed Ritonavir Crystals within Amorphous Solid Dispersions

“…Several mechanisms were considered for the origin of the disparit between the 2:1 geometric effect and the experimentally observed ∼3:1 difference in growth rates. Both the water content and the presence of surfactants can significantly impact the crystal growth rates within ASDs as reported previously. − , Copovidone is known to exhibit significant water absorption at high humidities such as those used in the experiments performed herein . For crystals seeded within the bulk, onset of crystal growth arose within ∼1 h, consistent with relatively fast water permeation throughout the copovidone films (<1 h).…”

Self-Association of Rafoxanide in Aqueous Media and Its Application in Preparing Amorphous Solid Dispersions

“…Nonsink Dissolution Testing. We conducted in vitro release testing of RAF spray-dried ASDs with a USP dissolution apparatus II 13 (Vankel dissolution apparatus, Model 7000, Palo Alto, CA, USA). The paddle speed was set at 50 rpm.…”

Development and Characterization of Films for Food Application Incorporating Porphyran Extracted from Porphyra dioica

“…These results show that both semi-refined porphyran and glycerol can be used to reduce the films Young's Modulus while affecting the UTS. They contribute to ramified structures, where interactions (hydrogen bonds, electrostatic and van der Waals interactions) between matrix components increase tensile strength and elasticity [72][73][74].…”