Characterizing and Exploring the Differences in Dissolution and Stability Between Crystalline Solid Dispersion and Amorphous Solid Dispersion

Abstract

Solid dispersion is one of the most effective ways to improve the dissolution of insoluble drugs. When the carrier can highly disperse the drug, it will increase the wettability of the drug and reduce the surface tension, thus improving the solubility, dissolution, and bioavailability. However, amorphous solid dispersions usually have low drug loading and poor stability. Therefore, the goal of this work is to study the increased dissolution and high stability of high drug-loading crystalline solid dispersion (CSD), and the difference in dissolution and stability of high-loading and low-loading amorphous solid dispersion (ASD). A CSD of nimodipine with a drug loading of 90% was prepared by wet milling, with hydroxypropyl cellulose (model: HPC-SL) and sodium dodecyl sulfate as stabilizers and spray drying. At the same time, the gradient drug-loaded ASD was prepared by hot melt extrusion with HPC-SL as the carrier. Each preparation was characterized by DSC, PXRD, FT-IR, SEM, and in vitro dissolution testing. The results indicated that the drug in CSD existed in a crystalline state. The amorphous drug molecules in the low drug-loading ASD were uniformly dispersed in the carrier, while the drug state in the high drug-loading ASD was aggregates of the amorphous drug. At the end of the dissolution assay, the 90% drugloading CSD increased cumulative dissolution to 60%, and the 10% drug-loading ASD achieved a cumulative dissolution rate of 90%.

Dissolution Improvement of Progesterone and Testosterone via Impregnation on Mesoporous Silica Using Supercritical Carbon Dioxide

“…As mentioned earlier, the release of impregnated drugs was fast with ~ 80-90% obtained for both TST and PRG in the first 2 min in comparison to only 25% of unimpregnated actives. The high dissolution rate of drug-silica preparations can be attributed to the drug amorphisation along with the improved wettability [11,112,113]. An increase in the surface area due to the distribution of drugs in the micropores as well as favourable wettability permits accelerated penetration of the aqueous media into the capillaries on the porous particles resulting in the faster dissolution of both TST and PRG.…”

Determination of Alteration in Micromeritic Properties of a Solid Dispersion: Brunauer-Emmett-Teller Based Adsorption and Other Structured Approaches

“…The dissolution studies of BEX and prepared solid dispersions using MLBG and POLO (equivalent to 5 mg of BEX) were performed at 100 rpm using dissolution apparatus (DS 8000; LABINDA, Navi Mumbai, India) in a hemispherical bottomed dissolution vessel in 900 ml of distilled water at 37 ± 0.5°C using USP type II apparatus (paddle type). At appropriate time intervals, aliquots of 5 ml were withdrawn and replaced with fresh dissolution medium [4,26]. The samples were filtered using a membrane filter of pore size 0.45 μm (Millipore Corp., Billerica, MA, USA) and quantified using HPLC.…”

“…Solid dispersion is one of the best alternatives to many other strategies in increasing solubility of poorly soluble drugs as it offers a variety of processing and excipient options that enhances the operational flexibility while formulating oral drug delivery systems [1][2][3]. Also, in solid dispersions, the poorly soluble drug sometimes gets transform into amorphous form in amorphous polymer matrix and possesses higher metastable energy state which leads to enhanced solubility and bioavailability of compound [4,5]. Improvement in the wettability of the drug (which is improved by direct contact with the hydrophilic matrix), particle size reduction, increased surface area, and transformation from crystalline to amorphous state has been considered as the key mechanism for enhancing dissolution and bioavailability of any drug by formation of dispersions [6,7].…”

Current Progress of Electrospun Nanocarriers for Drug Delivery Applications

“…The crystalline dispersion causes a thermodynamically stable matrix. This method is more efficient than a solid dispersion system and dissolution [51,52].…”