Preparation of a Novel Form of Gelatin With a Three-Dimensional Ordered Macroporous Structure to Regulate the Release of Poorly Water-Soluble Drugs.

In this study, a novel three-dimensional ordered macroporous gelatin (3DOMG) was fabricated as a carrier for increasing the solubility of poorly water-soluble drugs, offering sustained release and a high oral bioavailability. Polymethyl methacrylate nanospheres (257 nm) were used as a colloidal plastic framework to synthesize 3DOMG. Fenofibrate (FNB) was selected as a model drug and loaded onto 3DOMG by the adsorption equilibrium method. Detailed characterization showed that the FNB absorbed onto 3DOMG was in a microcrystalline state. A fluorescence experiment and the prepared drug microcrystal network gave further information on the physical state of the drug. A degradation experiment proved that 3DOMG was readily biodegradable. In vitro release testing showed that 3DOMG increased the dissolution rate of FNB and produced a sustained release. An in vivo pharmacokinetic study confirmed that 3DOMG improved the oral bioavailability compared with that of commercial sustained-release capsules. These findings confirm that 3DOMG can be regarded as a promising carrier for an oral drug delivery system.

Development of a novel starch with a three-dimensional ordered macroporous structure for improving the dissolution rate of felodipine.

In this study, silica nanospheres with different particle sizes were used as hard template for synthesis of a starch with a novel three-dimensional ordered macroporous structure (3DOMTS). As a pharmaceutical adjuvant, 3DOMTS was used to improve the dissolution rate and oral relative bioavailability of water-insoluble drugs. Felodipine (FDP) was chosen as a model drug and was loaded into the 3DOMTS by solvent evaporation. FDP loading into 3DOMTS with different pore sizes was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimeter (DSC), powder X-ray diffractometer (PXRD) and Fourier-Transform Infrared (FTIR). The results obtained showed that FDP was present in the pores in an amorphic or microcrystalline state. The in vitro dissolution results showed that 3DOMTS could effectively improve the dissolution rate of FDP in comparison with commercial common tablets. Pharmacokinetic results indicated that the oral relative bioavailability of self-made FDP-3DOMTS tablets were 184%, showing that 3DOMTS produced a significantly increased oral absorption of FDP. In conclusion, 3DOMTS exhibits the dual potential of improving the dissolution rate of poorly water soluble drugs and the novel filler produced by direct compression technology confirming that 3DOMTS will be useful for many applications in the field of pharmaceutics.

Preparation of starch macrocellular foam for increasing the dissolution rate of poorly water-soluble drugs.

Starch macrocellular foam (SMF), a novel natural bio-matrix material, was prepared by the hard template method in order to improve the dissolution rate and oral bioavailability of poorly water-soluble drugs. Nitrendipine (NDP) was chosen as a model drug and was loaded into SMF by the solvent evaporation method. SMF and the loaded SMF samples (NDP-SMF) were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy. In vitro drug release studies showed that SMF significantly increased the dissolution rate of NDP. In vivo studies showed that the NDP-SMF tablets clearly increased the oral bioavailability of NDP in comparison with the reference commercial tablets. All the results obtained demonstrated that SMF was a promising carrier for the oral delivery of poor water-soluble drugs.

Development of novel core-shell dual-mesoporous silica nanoparticles for the production of high bioavailable controlled-release fenofibrate tablets.

Novel core-shell dual-mesoporous silica nanoparticles (DMSN) were successfully prepared as a carrier in order to improve the dissolution of fenofibrate and obtain an oral highly bioavailable controlled-release drug delivery system using the osmotic pump technology. Fenofibrate was loaded into DMSN by an adsorption method. The solid state properties of fenofibrate in DMSN, before and after drug loading, were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption analysis (BET), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). In vitro release tests showed that DMSN increased the dissolution rate of fenofibrate and produced zero-order release in push-pull osmotic pump tablets (OPT). The relative bioavailability of OPT was 186.9% in comparison with the commercial reference product. In summary, osmotic pump technology in combination with solid dispersion technology involving nanometer materials is a promising way for achieving the oral delivery of poorly water-soluble drugs.

Development of an oral push-pull osmotic pump of fenofibrate-loaded mesoporous silica nanoparticles.

In this study, mesoporous silica nanoparticles (MSNs) were used to prepare an oral push-pull osmotic pump. Fenofibrate, the selected model drug, was firstly loaded into the MSNs, followed by a suspending agent consisting of a drug layer of push-pull osmotic pump. Fenofibrate-loaded MSNs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption analysis, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) analysis, and Fourier-transform infrared (FT-IR) spectroscopy. Polyethylene oxide of molecular weight (MW) 100,000 and polyethylene oxide of MW 6,000,000 were selected as the suspending agent and the expanding agent, respectively. Cellulose acetate was used as the semipermeable membrane, along with polyethylene glycol 6,000 to increase the flexibility and control the membrane permeability. The in vitro dissolution studies indicated that the osmotic pump tablet combined with MSNs was able to deliver fenofibrate in an approximately zero-order manner in 24 hours. A pharmacokinetic study showed that, although the maximum plasma concentration of the osmotic pump was lower than that of the reference formulation, the relative bioavailability was increased, indicating that the osmotic pump was more efficient than the reference tablets. Therefore, using MSNs as a carrier for poorly water-soluble drugs is an effective method for preparing osmotic pump tablets.

Synthesis of novel core-shell structured dual-mesoporous silica nanospheres and their application for enhancing the dissolution rate of poorly water-soluble drugs.

Novel core-shell dual-mesoporous silica nanospheres (DMSS) with a tunable pore size were synthesized successfully using a styrene monomer as a channel template for the core and cetyltrimethyl ammonium bromide (CTAB) as a channel template for the shell in order to improve the dissolution rate of poorly water-soluble drugs. Simvastatin was used as a model drug and loaded into DMSS and the mesoporous core without the shell (MSC) by the solvent evaporation method. The drug loading efficiency of DMSS and MSC were determined by thermogravimetric analysis (TGA) and ultraviolet spectroscopy (UV). Characterization, using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR) showed that simvastatin adsorbed in DMSS and MSC was in an amorphous state, and in vitro release test results demonstrated that both DMSS and MSC increased the water solubility and dissolution rate of simvastatin. The shell structure of DMSS was able to regulate the release of simvastatin compared with MSC. It is worth noting that DMSS has significant potential as a carrier for improving the dissolution of poorly water-soluble drugs and reducing the rapid release.

Preparation of a push-pull osmotic pump of felodipine solubilized by mesoporous silica nanoparticles with a core-shell structure.

The purpose of this study was to use mesoporous silica nanoparticles to improve drug dissolution after releasing from a push-pull osmotic pump. Felodipine was selected as the model drug and it was first incorporated into mesoporous silica nanoparticles prepared previously by the solvent evaporation method after we had examined a series of drug-silica ratios to load the drug into the mesoporous silica nanoparticles in order to find the optimum ratio for drug loading. Then, the drug-carrier was added to the drug-layer of the push-pull osmotic pump. PEO (Mw 100,000) was used as a suspending agent and PEO (Mw 6,000,000) was used as an expanding agent. The core tablets were coated with cellulose acetate (CA) as a semipermeable membrane containing polyethylene glycol (PEG) 6000 to control the membrane permeability. In vitro dissolution studies showed that the self-made osmotic pump tablets were able to deliver felodipine in an approximately zero-order manner in 12 h. A pharmacokinetic study was carried out to compare the new system with reference sustained-release tablets. It was found that the half-life of felodipine in the push-pull osmotic pump tablets was prolonged 1.8-fold, the bioavailability was increased 18% and the maximum plasma concentration reduced by 25%. In conclusion, using the self-made push-pull osmotic pump in combination with mesoporous silica nanoparticles was able to effectively increase the bioavailability of felodipine and reduce fluctuations in its plasma concentration.