One-step preparation of drug-containing microparticles to enhance the dissolution and absorption of poorly water-soluble drugs using a 4-fluid nozzle spray drier.

We studied the use of a 4-fluid nozzle spray drier as a new one-step method for preparing drug-containing microparticles to enhance the dissolution and absorption of poorly water-soluble drugs. We employed ethenzamide (EZ) and flurbiprofen (FP) as poorly water-soluble drugs and lactose (LAC) and mannitol (MAN) as water-soluble carriers for microparticles. EZ-ethanol or FP-acetone/methanol (2:1) solutions and aqueous solutions of LAC or MAN were simultaneously supplied through different liquid passages of a 4-fluid nozzle spray drier and then dried to obtain LAC or MAN microparticles containing EZ or FP. The dissolution of EZ from the EZ/LAC and EZ/MAN microparticles was much faster than that from EZ powder. The dissolution of EZ was more rapid from the EZ/MAN microparticles than the EZ/LAC microparticles. The dissolution of FP from the FP/MAN microparticles was greatly enhanced because of large effective surface area of FP dispersed in microparticles following rapid dissolution of MAN. The absorption of FP after oral administration of the FP/MAN microparticles to rats was markedly increased. The results demonstrate that the 4-fluid nozzle spray drier can be used for the one-step preparation of drug-containing microparticles that enhance the dissolution and absorption of poorly water-soluble drugs and that overcome the problem of finding a common solvent for drugs and carriers.

Preparation of polymeric submicron particle-containing microparticles using a 4-fluid nozzle spray drier.

PURPOSE: We studied a novel method for preparing polymeric submicron particle-containing microparticles using a 4-fluid nozzle spray drier. METHOD: Ethylcellulose (EC) and poly(lactic-co-glycolic acid) (PLGA), either alone or in combination with polyethylenimine (PEI), were used as polymers to produce submicron particles, and mannitol (MAN) was used as a water-soluble carrier for the microparticles. The polymer and MAN solutions were supplied through different liquid passages of a 4-fluid nozzle and then dried to obtain MAN microparticles containing EC or PLGA submicron particles. The polymer/MAN ratio was controlled by changing the concentration of the polymer and MAN solutions. EC or PLGA microparticles were observed via scanning electron microscopy, and the size of microparticles was determined by image analysis. The particle size distribution of EC or PLGA submicron particles was measured with a super dynamic light scattering spectrophotometer. RESULTS: The method generated submicron-sized (<1 microm) particles of EC and PLGA. The mean diameters of EC and PLGA particles at a polymer/MAN ratio of 1:10 were 631 and 490 nm, respectively. The mean diameter of PLGA particles decreased as the PLGA/MAN ratio was reduced, reaching approximately 200 nm at a PLGA/MAN ratio of 1:100. The mean diameter of PLGA/PEI particles at PLGA/PEI/MAN ratios of 1:0.5:10 and 1:0.5:100 were 525 and 223 nm, respectively, and their zeta potentials were +50.8 and +58.2 mV, respectively. The size of EC submicron particles could be controlled by varying the spray conditions. CONCLUSIONS: This study demonstrated that it is possible to prepare polymeric submicron particles dispersed in MAN microparticles in a single process using the 4-fluid nozzle spray drying method. Cationic PLGA particles with a diameter of approximately 200 nm could be prepared by adding PEI, suggesting the possibility of its use as a carrier for delivering DNA into cells. The precipitation of EC may occur by the mutual dispersion and mixing of solvents after collision of EC and MAN mists by antisolvent effect, thereby producing MAN microparticles containing EC submicron particles.

Preparation of two-drug composite microparticles to improve the dissolution of insoluble drug in water for use with a 4-fluid nozzle spray drier.

In this study, we used a novel 4-fluid nozzle spray drier to prepare composite microparticles of a water-insoluble drug, flurbiprofen (FP), and a water-soluble drug, sodium salicylate (SS), for the purpose of improving the water solubility of FP. An ethanol solution of FP and an aqueous SS solution were simultaneously introduced through different liquid passages in the 4-fluid nozzle spray drier and then spray-dried. Quantitative elemental analysis suggested that the FP/SS ratio in each composite microparticle was nearly the same as the formulation ratio. We also found that SS and FP exist in a low crystallinity state in the composite particles. Release of FP from dissolved composite microparticles was markedly improved because of an increase in the effective surface area following rapid dissolution of SS. This study shows that it is possible to prepare FP-SS composite microparticles using a 4-fluid nozzle spray drier in single process and that this can improve the ability of FP to dissolve in water.