This review covers recent developments in the area of particle engineering via spray drying. The last decade has seen a shift from empirical formulation efforts to an engineering approach based on a better understanding of particle formation in the spray drying process. Microparticles with nanoscale substructures can now be designed and their functionality has contributed significantly to stability and efficacy of the particulate dosage form. The review provides concepts and a theoretical framework for particle design calculations. It reviews experimental research into parameters that influence particle formation. A classification based on dimensionless numbers is presented that can be used to estimate how excipient properties in combination with process parameters influence the morphology of the engineered particles. A wide range of pharmaceutical application examples—low density particles, composite particles, microencapsulation, and glass stabilization—is discussed, with specific emphasis on the underlying particle formation mechanisms and design concepts.

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Pharmaceutical particle engineering via spray drying.

With the rapidly growing popularity and sophistication of inhalation therapy, there is an increasing demand for tailor-made inhalable drug particles capable of affording the most efficient delivery to the lungs and the most optimal therapeutic outcomes. To cope with this formulation demand, a wide variety of novel particle technologies have emerged over the past decade. The present review is intended to provide a critical account of the current goals and technologies of particle engineering for the development of pulmonary drug delivery systems. These technologies cover traditional micronization and powder blending, controlled solvent crystallization, spray drying, spray freeze drying, particle formation from liquid dispersion systems, supercritical fluid processing and particle coating. The merits and limitations of these technologies are discussed with reference to their applications to specific drug and/or excipient materials. The regulatory requirements applicable to particulate inhalation products are also reviewed briefly.

Particle Engineering for Pulmonary Drug Delivery

Solid lipid nanoparticles (SLNs) are nanocarriers developed as substitute colloidal drug delivery systems parallel to liposomes, lipid emulsions, polymeric nanoparticles, and so forth. Owing to their unique size dependent properties and ability to incorporate drugs, SLNs present an opportunity to build up new therapeutic prototypes for drug delivery and targeting. SLNs hold great potential for attaining the goal of targeted and controlled drug delivery, which currently draws the interest of researchers worldwide. The present review sheds light on different aspects of SLNs including fabrication and characterization techniques, formulation variables, routes of administration, surface modifications, toxicity, and biomedical applications.

Solid Lipid Nanoparticles: Emerging Colloidal Nano Drug Delivery Systems

Spray drying formulation of amorphous solid dispersions.

Spray drying technique. I: Hardware and process parameters.

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

We studied a novel method for preparing polymeric submicron particle-containing microparticles using a 4-fluid nozzle spray drier. 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. The method generated submicron-sized (<1 μm) 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 ∼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. 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 ∼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 polymeric submicron particle-containing microparticles using a 4-fluid nozzle spray drier.

Effect of physical properties of carrier particles on drug emission from a dry powder inhaler device

Design of Rapidly Disintegrating Oral Tablets Using Acid-Treated Yeast Cell Wall: A Technical Note Submitted: August 5, 2003; Accepted: November 13, 2003 Tetsuya Ozeki, Yuriko Yasuzawa, Hideyo Katsuyama, Yuuki Takashima, Takahide Kasai, Takahiro Eguchi, Hisaya Kakiuchi, Hiroshi Yuasa, and Hiroaki Okada Department of Pharmaceutics and Drug Delivery, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan Applied Research Center, Research & Development Division, Kirin Brewery Co, 3 Miyahara, Takasaki, Gunma 370-1295, Japan

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Design of rapidly disintegrating oral tablets using acid-treated yeast cell wall: a technical note.

The purpose of this research was to investigate the effect of the shape of sodium salicylate (SS) particles on the physical properties as well as the in vitro aerosol performance of the granules granulated by the pressure swing granulation method. SS was pulverized with a jet mill (JM) to prepare the distorted particles, and SS aqueous solution was spray dried (SD) to prepare the nearly spherical particles. The particle size distribution, crushing strength, and pore size distribution of the granules were measured. The adhesive force of the primary particles in the granules was calculated according to Rumpf's equation. The in vitro aerosol performance of the granules was evaluated using a cascade impactor. Both JM and SD particles can be spherically granulated by the pressure swing granulation method without the use of a binder. The size of SD granules was smaller than that of JM granules. Although the crushing strength of the JM and SD granules is almost the same, the internal structures of JM granules and SD granules were found to differ, and the SD particles appear to have been condensed uniformly, resulting in a nearly spherical shape. In the inhalation investigation, the percentage of SS particles of appropriate size delivered to the region for treatment was noticeably higher for SD granules than for JM granules. This finding might be because the adhesive force of the SD primary particles was smaller than that of the JM primary particles in the granules and because the SD granules could be easily separated by air current to obtain the primary particles.

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Effect of shape of sodium salicylate particles on physical property and in vitro aerosol performance of granules prepared by pressure swing granulation method.

Yuuki Takashima

Papers

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

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

Effect of physical properties of carrier particles on drug emission from a dry powder inhaler device

Design of rapidly disintegrating oral tablets using acid-treated yeast cell wall: a technical note.

Effect of shape of sodium salicylate particles on physical property and in vitro aerosol performance of granules prepared by pressure swing granulation method.