Abstract
This work explored absorption efficacy via an in vivo imaging system and parallel artificial membrane penetration in indomethacin (IMC) solid dispersion (SD) systems. Two different polymer excipients—hydroxypropyl methylcellulose (HPMC) and Kollicoat IR as precipitation inhibitors (PIs)—combined with mesoporous silica nanoparticles (MSNs) as carriers were investigated. The IMC–SDs were prepared using the solvent evaporation method and characterized by solubility analysis, infrared (IR) spectroscopy, powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FESEM), and differential scanning calorimetry (DSC). It was confirmed that IMC successfully changed into an amorphous state after loading into the designed carriers. The in vitro release and stability experiments were conducted to examine the in vitro dissolution rates of IMC–SDs combined with HPMC and Kollicoat IR as PIs which both improved approximately three-fold to that of the pure drug. Finally, in vivo studies and in vitro parallel artificial membrane penetration (PAMPA) experiments ensured the greater ability of enhancing the dissolution rates of pure IMC in the gastrointestinal tract by oral delivery. In brief, this study highlights the prominent role of HPMC and Kollicoat IR as PIs in MSN SD systems in improving the bioavailability and gastrointestinal oral absorption efficiency of indomethacin.
Highlights
Biopharmaceutics classification system (BCS) Class II drugs are characterized by low solubility and high membrane permeability, so that the dissolution of drugs from dosage formulation is the ultimate rate-limiting step [1], resulting in high permeability but low bioavailability
The results showed that the dissolution rate of solid dispersion (SD) (i.e., IMC–mesoporous silica nanoparticles (MSNs), IMC–MSNs@Kollicoat IR, and IMC–MSNs@hydroxypropyl methylcellulose E5 (HPMC)) stored for two months at 25 ◦ C and 60% relative humidity (RH) was similar to that of freshly prepared SDs
This study manifested a feasible scheme using the solvent evaporation method to understand the amorphous form of IMC–SDs with MSNs
Summary
Biopharmaceutics classification system (BCS) Class II drugs are characterized by low solubility and high membrane permeability, so that the dissolution of drugs from dosage formulation is the ultimate rate-limiting step [1], resulting in high permeability but low bioavailability. Many strategies have been applied to improve the dissolution rate and bioavailability of active pharmaceutical ingredients (APIs) including formulation changes, industry strategies, method optimum, etc. A widely investigated method to circumvent solubility/dissolution-limited bioavailability is to change crystalline drugs into amorphous forms. The optimum ability of the amorphous state is to generate supersaturation solutions possessing high internal free energy to increase the solubility and dissolution rate of insoluble drugs. Precipitation inhibitors (PIs) play a key role when amorphous form crystalline drugs change from the amorphous form to a crystalline state in solution.
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