Preparation of PLGA Nanoparticles by Milling Spongelike PLGA Microspheres.

Currently, emulsification-templated nanoencapsulation techniques (e.g., nanoprecipitation) have been most frequently used to prepare poly-,-lactide--glycolide (PLGA) nanoparticles.

Protein Loading into Spongelike PLGA Microspheres.

A self-healing microencapsulation process involves mixing preformed porous microspheres in an aqueous solution containing the desired protein and converting them into closed-pore microspheres. Spongelike poly-d,l-lactide--glycolide (PLGA) microspheres are expected to be advantageous to protein loading through self-healing. This study aimed to identify and assess relevant critical parameters, using lysozyme as a model protein.

Assessment of Residual Solvent and Drug in PLGA Microspheres by Derivative Thermogravimetry.

Thermogravimetry does not give specific information on residual organic solvents in polymeric matrices unless it is hyphenated with the so-called evolved gas analysis. The purpose of this study was to apply, for the first time, derivative thermogravimetry (DTG) to characterize a residual solvent and a drug in poly--lactide--glycolide (PLGA) microspheres. Ethyl formate, an ICH class 3 solvent, was used to encapsulate progesterone into microspheres.

Qualification of Non-Halogenated Organic Solvents Applied to Microsphere Manufacturing Process.

As a non-halogenated dispersed solvent, ethyl acetate has been most commonly used for the manufacturing of poly-d,l-lactide--glycolide (PLGA) microspheres. However, ethyl acetate-based microencapsulation processes face several limitations. This study was aimed at proposing ethyl formate as an alternative.

Merits of sponge-like PLGA microspheres as long-acting injectables of hydrophobic drug.

Our study was initiated to challenge the preconception that nonporous PLGA microspheres with compact matrices should be used to develop long-acting depot injectables of hydrophobic drugs. A simple, new oil-in-water emulsion technique was utilized to produce porous PLGA microspheres with a sponge-like skeleton. Then, their applicability to developing sustained-release depots of hydrophobic drugs was explored in this study.

Applicability of non-halogenated methyl propionate to microencapsulation.

Applicability of methyl propionate to microencapsulation was evaluated with regard to volatility, capability of forming emulsions, and their quality. An emulsion-based technique was then developed to encapsulate progesterone into poly-d,l-lactide-co-glycolide microspheres. Their characteristics were compared with those prepared using ethyl acetate.

Concepts and practices used to develop functional PLGA-based nanoparticulate systems.

The functionality of bare polylactide-co-glycolide (PLGA) nanoparticles is limited to drug depot or drug solubilization in their hard cores. They have inherent weaknesses as a drug-delivery system. For instance, when administered intravenously, the nanoparticles undergo rapid clearance from systemic circulation before reaching the site of action.

Core-shell-type lipid-polymer hybrid nanoparticles as a drug delivery platform.

Unlabelled: The focus of nanoparticle design over the years has evolved toward more complex nanoscopic core-shell architecture using a single delivery system to combine multiple functionalities within nanoparticles. Core-shell-type lipid-polymer hybrid nanoparticles (CSLPHNs), which combine the mechanical advantages of biodegradable polymeric nanoparticles and biomimetic advantages of liposomes, have emerged as a robust and promising delivery platform. In CSLPHNs, a biodegradable polymeric core is surrounded by a shell composed of layer(s) of phospholipids.

Utilization of catalytic hydrolysis of ethyl acetate for solvent removal during microencapsulation.

The objective of this study was to apply the specific acid-catalysed hydrolysis of ethyl acetate to completing solvent extraction during an emulsion-based microencapsulation process. The dispersed phase consisting of poly-D,L-lactide-co-glycolide and ethyl acetate was emulsified in an acid catalyst containing aqueous phase. Catalytic hydrolysis of ethyl acetate led to its continual leaching from the dispersed phase of the emulsion, thereby triggering microsphere hardening with high efficiency.

Application of acid-catalyzed hydrolysis of dispersed organic solvent in developing new microencapsulation process technology.

The aim of this study was to evaluate a new microencapsulation technology employing an acid-catalyzed solvent extraction method in conjunction to an emulsion-based microencapsulation process. Its process consisted of emulsifying a dispersed phase of poly(D,L-lactide-co-glycolide) and isopropyl formate in an aqueous phase. This step was followed by adding hydrochloric acid to the resulting oil-in-water emulsion, in order to initiate the hydrolysis of isopropyl formate dissolved in the aqueous phase.

Investigation on structural integrity of PLGA during ammonolysis-based microencapsulation process.

The objective of this study was to gain insights into the structural integrity of PLGA during an ammonolysis-based microencapsulation process. PLGA (lactide:glycolide ratio=75:25; M(w)=25,925 g/mol) was dissolved in ethyl acetate or isopropyl formate (3-6 ml), which was emulsified in an aqueous phase. Ammonia, being added to the emulsions, reacted with the dispersed solvents to yield water-miscible solvents.

Nonhalogenated solvent-based solvent evaporation process useful in preparation of PLGA microspheres.

The objective of this study was to develop an isopropyl formate-based evaporation process useful in producing poly-D,L-lactide-co-glycolide microspheres. Surprisingly, the evaporating tendency of isopropyl formate was comparable to that of methylene chloride and far better than that of ethyl acetate. After optimization of the isopropyl formate-based process, progesterone was encapsulated into microspheres.

Another paradigm in solvent extraction-based microencapsulation technologies.

The objectives of this study were to apply a base-driven reaction to developing a new microencapsulation technique to prepare progesterone-containing poly-D,L-lactide-co-glycolide microspheres. Nonhalogenated ester solvents such as ethyl acetate and ethyl formate were used as dispersed solvents. After an oil-in-water emulsion was prepared, a sodium hydroxide solution was added to trigger base-catalyzed hydrolysis of organic solvents dissolved in the aqueous phase.

Ammonolysis-based microencapsulation technique using isopropyl formate as dispersed solvent.

The objectives of this study were to develop an ammonolysis-based microencapsulation technique using a nonhalogenated isopropyl formate and to evaluate its feasibility in preparing poly-D,L-lactide-co-glycolide microspheres. The choice of isopropyl formate was based on its great reactivity toward ammonolysis and acceptance as a flavoring agent for human food by regulatory agencies. Progesterone was used as a model drug for microencapsulation.

Application of column-switching HPLC method in evaluating pharmacokinetic parameters of zaltoprofen and its salt.

The objective of this study was to compare the pharmacokinetic parameters of zaltoprofen and those of its sodium salt in rats. Zaltoprofen, a potent non-steroidal anti-inflammatory agent, was virtually insoluble in water, but its sodium salt had excellent water solubility. To investigate the effect of aqueous solubility differences upon their pharmacokinetic parameters, minicapsules containing the drug powders were administrated orally to rats, and blood samples were taken via the common carotid artery.

Ammonolysis-induced solvent removal: a facile approach for solidifying emulsion droplets into PLGA microspheres.

An ammonolysis-based microencapsulation technique useful for the preparation of biodegradable microspheres was described in this study. A dispersed phase consisting of poly- d, l-lactide- co-glycolide, progesterone, and methyl chloroacetate was emulsified in an aqueous phase. Upon addition of ammonia solution, the emulsion droplets were quickly transformed into poly- d, l-lactide- co-glycolide microspheres laden with progesterone.

Effect of pharmaceutical excipients on aqueous stability of rabeprazole sodium.

The chemical stability of a proton-pump inhibitor, rabeprazole sodium, was evaluated in simulated intestinal fluid (pH 6.8) containing various 'Generally Recognized As Safe (GRAS)'-listed excipients, including Brij 58, Poloxamer 188, Cremophor RH40, Gelucire 44/14 and PEG 6000. After incubation at 37 and 60 degrees C, the amounts of rabeprazole and its degradation product, thioether-rabeprazole, were quantitated by HPLC analysis.

Characterization of dual layered pellets for sustained release of poorly water-soluble drug.

The aim of this study was to develop pellet formulations that could be used to improve the dissolution and bioavailability of a poorly water-soluble model drug, cisapride. Six different types of pellets were prepared by coating sugar spheres in a fluidized bed coater. When the sugar spheres were single layered containing cisapride and solubilizer such as polysorbate 80, the resulting pellets provided an instant release of cisapride in the simulated gastric fluid.

Reverse micelle-based microencapsulation of oxytetracycline hydrochloride into poly-d,l-lactide-co-glycolide microspheres.

The objectives of this study were to solubilize oxytetracycline hydrochloride (HCl) in reverse micelles to prepare poly-d,l-lactide-co-glycolide (PLGA) microspheres and to explore parameters affecting its encapsulation efficiency. Oxytetracycline HCl was dissolved in the reverse micelles consisting of cetyltrimethylammonium bromide, water, and ethyl formate. A PLGA polymer was then dissolved in the reverse micellar solution, and a modified solvent quenching procedure was carried out to prepare PLGA microspheres.

Characterization of itraconazole semisolid dosage forms prepared by hot melt technique.

The objective of this study was to formulate itraconazole semisolid dosage forms and characterize their physicochemical properties. Itraconazole and excipients such as polysorbate 80, fatty acids, fatty alcohols, oils and organic acids were melted at 160 degrees C. The fused solution was then cooled immediately at -10 degrees C to make wax-like semisolid preparations.

Degradation patterns of tetracycline antibiotics in reverse micelles and water.

The objective of this study was to determine the chemical stability of tetracycline and oxytetracycline hydro-chlorides in reverse micelles. Their reverse micellar solutions were prepared using cetyltrimethylammonium bromide, water and ethyl formate. The aqueous solutions of the tetracycline antibiotics were also prepared for comparison.

Improvement of interfacial protein stability by CHAPS.

Emulsification of aqueous protein solutions in methylene chloride triggered the formation of water-insoluble aggregates at a water/methylene chloride interface. As a result, the amounts of beta-lactoglobulin and ovalbumin recovered in water were 36 and 44%, respectively. Addition of 5 mM: CHAPS in the aqueous phase raised the degree of beta-lactoglobulin recovery to 96%.

Effects of aqueous phase composition upon protein destabilization at water/organic solvent interface.

The objective of this study was to evaluate the effects of an aqueous phase composition upon the destabilization of lactoglobulin toward emulsification. Eight different buffers were used to make aqueous lactoglobulin solutions at pH 5.6-9.

Preparation of mucoadhesive microspheres containing antimicrobial agents for eradication of H. pylori.

Mucoadhesive microspheres containing either amoxicillin or clarithromycin were prepared via the interpolymer complexation of poly(acrylic acid) (PAA) with poly(vinyl pyrrolidone) (PVP) and solvent diffusion method. The complexation between the PAA and PVP in an ethanol/water mixture was confirmed by the change in the transmittance of the solution as a function of repeating PAA and PVP unit ratio. The loading efficiency of clarithromycin in the complex microspheres was higher than that of amoxicillin due to the stronger interaction of clarithromycin with the PAA.

Development of new reverse micellar microencapsulation technique to load water-soluble drug into PLGA microspheres.

The objective of this study was to develop a new reverse micelle-based microencapsulation technique to load tetracycline hydrochloride into PLGA microspheres. To do so, a reverse micellar system was formulated to dissolve tetracycline hydrochloride and water in ethyl formate with the aid of cetyltrimethylammonium bromide. The resultant micellar solution was used to dissolve 0.