Studies on mechanism of enhanced dissolution of albendazole solid dispersions with crystalline carriers

Abstract

The main purpose of this research was to study the mechanism of drug release from solid dispersions of albendazole, giving special emphasis to particle size of the drug in solid dispersions. Solid dispersions were prepared using three different carriers, mixing ratios and methods in an attempt to improve the solubility and dissolution rate of albendazole. The mechanism of enhanced dissolution was investigated by a novel dissolution technique as an adjunct to phase solubility study, wettability test, differential scanning calorimetry, X-ray diffractometry, infrared spectroscopy and scanning electron microscopy. The solubility of albendazole was greater with albendazole-poloxamer 407 system, while polyethylene glycol dispersions showed predominant wettability. Physical mixtures showed enhanced dissolution compared with the pure drug, due to improved wetting and solubilization of drug in the diffusion layer offering carrier-rich microenvironment. Preparation of solid dispersion further improved the dissolution compared to the physical mixture, owing to increased surface area for mass transfer, thermodynamically enhanced dissolution of a higher energy amorphous form from the carrier, in addition to improved wetting and solubilization. All carriers showed comparable degree of drug particle size reduction, whereas mixing ratio and method of preparation substantially affected the particle size. Intermolecular association of drug with the carrier led to inhibition of drug recrystallization.

Dissolution Enhancement and Formulation of Rapid-Release Lornoxicam Mini-Tablets

“…In the case of the physical mixture, this behaviour could be possibly attributed to the dilution effect of the carrier, especially when present at a high ratio in these samples (1:5 weight ratio), and/or melting of the carrier at a lower temperature causing dissolution of drug crystals in the molten mass of the carrier and the formation of amorphous LOR during the DSC scan. Similar observations have previously been reported . However, in the case of the co‐evaporate systems with both PEG and PLU, the disappearance of LOR melting exotherm may be because of the interaction between the drug and the carrier as pointed out from the FT‐IR study, and thus suggesting possible conversion of crystalline LOR to an amorphous structure within the carrier matrix.…”

“…Similar observations have previously been reported. [35][36][37][38] However, in the case of the co-evaporate systems with both PEG and PLU, the disappearance of LOR melting exotherm may be because of the interaction between the drug and the carrier as pointed out from the FT-IR study, and thus suggesting possible conversion of crystalline LOR to an amorphous structure within the carrier matrix. Similar behaviour was also observed in the case of NEU physical mixtures, adsorbates and co-adsorbates.…”

Enhancement of solubility and dissolution of glipizide by solid dispersion (kneading) technique

“…whichThis mixture was then subsequently passed through meshs no. 40 and stored in a dessicator for 48 h. [12,13] The Kneading method (KM) was used for the preparation of solid dispersion (SD). Eight different drug: Carrier ratios (1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7 and 1:8) were used.…”

Dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs with poor water solubility

“…Generally, when the structure of the drug is more amorphous, greater increases in the drug dissolution rate from SD can be obtained. A simple method to govern the drug crystallinity of SD is to increase the ratio of carrier to drug [58,59]. However, the addition of carrier cannot enhance drug release constantly until it reaches a particular level.…”