Solubility enhancement of a poorly water soluble drug by forming solid dispersions using mechanochemical activation

Abstract

Mechanochemical activation is a practical cogrinding operation used to obtain a solid dispersion of a poorly water soluble drug through changes in the solid state molecular aggregation of drug-carrier mixtures and the formation of noncovalent interactions (hydrogen bonds) between two crystalline solids such as a soluble carrier, lactose, and a poorly soluble drug, indomethacin, in order to improve its solubility and dissolution rate. Samples of indomethacin and a physical mixture with a weight ratio of 1:1 of indomethacin and lactose were ground using a high speed vibrating ball mill. Particle size was determined by electron microscopy, the reduction of crystallinity was determined by calorimetry and transmission electron microscopy, infrared spectroscopy was used to find evidence of any interactions between the drug and the carrier and the determination of apparent solubility allowed for the corroboration of changes in solubility. Before grinding, scanning electron microscopy showed the drug and lactose to have an average particle size of around 50 and 30 μm, respectively. After high speed grinding, indomethacin and the mixture had a reduced average particle size of around 5 and 2 μm, respectively, showing a morphological change. The ground mixture produced a solid dispersion that had a loss of crystallinity that reached 81% after 30 min of grinding while the drug solubility of indomethacin within the solid dispersion increased by 2.76 fold as compared to the pure drug. Drug activation due to hydrogen bonds between the carboxylic group of the drug and the hydroxyl group of lactose as well as the decrease in crystallinity of the solid dispersion and the reduction of the particle size led to a better water solubility of indomethacin.

Comparative Studies on Dissolution and Bioavailability of Tamoxifen Citrate Loaded Binary and Ternary Solid Dispersions

“…A coground method has been reported [11] , in which a poorly water soluble drug was co-ground with water soluble polymers in the presence of small amount of water at controlled temperature. Although the composition of the coground mixture is similar to that of SD's, the drug crystallinity is maintained to some extent [12].From literature, physically unstable properties have been also reported in coground mixtures compared with melting method [13].…”

Enhancement of the Dissolution Rate of Indomethacin by Solid Dispersions in Low-substituted Hydroxypropyl Cellulose

“…DSC studies will be necessary to complete these studies on the decline in crystallinity. 5a) has an endothermic peak at 160.99° with low crystallinity (116.05 J/g) [42] . Fig.…”

Interaction of the Nonsteroidal Anti-inflammatory Drug Indomethacin with Micelles and Its Release

“…The water solubility of IMC in neat water is very low and is reported as 14 μg/mL (39 μM). 46 Therefore, we have maintained the concentration of IMC solution in neat water as 35 μM. The motivation of our study is to endeavor the photophysical properties of IMC in micelles.…”

“…In our case, the concentration of micelles is several times higher than drug (IMC). The water solubility of IMC in neat water is very low and is reported as 14 μg/mL (39 μM) . Therefore, we have maintained the concentration of IMC solution in neat water as 35 μM.…”