Stabilisation of amorphous ibuprofen in Upsalite, a mesoporous magnesium carbonate, as an approach to increasing the aqueous solubility of poorly soluble drugs

Abstract

One attractive approach to increase the aqueous solubility and thus the bioavailability of poorly soluble drugs is to formulate them in their amorphous state since amorphous compounds generally exhibit higher apparent solubilities than their crystalline counterparts. In the current work, mesoporous magnesium carbonate was used to stabilise the amorphous state of the model substance ibuprofen. Crystallisation of the drug was completely supressed in the formulation, resulting in both a higher apparent solubility and a three times faster dissolution rate of the drug where the drug release was shown to be diffusion controlled. It was also shown that the formulation is stable for at least three months when stored at 75% relative humidity. The simple synthesis together with a high loading capacity and narrow pore size distribution of the mesoporous magnesium carbonate is foreseen to offer great advantages in formulations of poorly soluble drugs.

Investigating the Effects of Loading Factors on the In Vitro Pharmaceutical Performance of Mesoporous Materials as Drug Carriers for Ibuprofen

“…Figure 3 shows that pure IBU was a crystalline substance with sharp distinct peaks observed at 2θ of 6.0°, 12.1°, 16.5°, 18.7°, 20.1° and 22.1°, which were in good agreement with the previous report [16]. Both S244FP and NS2 carriers were amorphous without any distinctive peak.…”

“…In the immersion method, the porous materials are immersed into a concentrated drug solution for the adsorption of drug molecules on the walls of the pores, and then, the drug loaded mesoporous materials are recovered through different approaches, such as filtration, slow evaporation, spray drying and rotary evaporation [7]. The properties of the mesoporous carriers, including the particle size/morphology, pore diameter, total surface area and volume and surface chemistry, can affect the drug loading efficiency and release rate [3,4,6,9,10,11,12,13,14,15,16]. It has also been found that the loading procedure is a crucial factor affecting the drug loading efficiency, packing of the drug molecules in the pores and thereafter the release kinetics.…”

Diffusion-Controlled Drug Release From the Mesoporous Magnesium Carbonate Upsalite ®

“…[7][8][9][10] In our previous work, the novel mesoporous and amorphous material Upsalite ® was investigated as a phase stabilizer of amorphous ibuprofen to increase its dissolution rate. [11][12][13][14] Upsalite ® consists of magnesium carbonate (MgCO 3 ) that is "generally recognized as safe" by the FDA. It has a large specific surface area (typically 300-800 cm 2 /g) and a narrow pore-size distribution (usually 6-8 nm), and these material properties have been associated with high loading of ibuprofen (30%) and suppressed crystallization.…”

Kinetics and Adsorption Isotherm of Ibuprofen onto Grafted β-CD/Chitosan Polymer

“…These drugs with poor aqueous solubility subsequently have low bioavailability, which can limit their therapeutic efficacy (Zhang et al, 2014). In this study, we shed more light on the interactions between poorly soluble drug and the carrier metrics, the equilibrium and the kinetic adsorption models of (Ibu) on CD-grafted chitosan polymer were investigated.…”