• Journal of Pharmaceutical Investigation
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• v.29 no.2
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• pp.99-103
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• 1999

Self-Emulsifying System(SES), an isotropic mixture of oil and surfactant which forms oil-in-water emulsion, is expected to improve in vitro drug dissolution and enhance in vivo drug absorption. A poorly water soluble drug, ibu-profen(IBP) was incorporated into the SES to improve absorption, and enhance bioavailability of drug. Medium chain triglyceride, glyceryl tricaprylate(GTC) as an oil, and Tween 85 as a surfactant were used to formulate SES. To characterize SESs with various concentrations of Tween 85, the phase separation and solubility of IBP-SEDDS containing IBP as a function of Tween 85 concentration were conducted, and the particle size was measured using photon correlation spectroscopic method. The SES with optimal concentration of Tween 85(35%(w/w)) was selected based on its high drug loading, small particle size and low surfactant concentration. After an oral administration of IBP-SEDDS and IBP suspension in methyl cellulose equivalent to 40.0 mg/kg to rats, the pharmacokinetic parameters were compared. The $C_{max}(163.17\;vs\;88.82\;{\mu}g/ml)$, $AUC(12897.01\;vs\;8751.13\;{\mu}g\;min/ml)$ and Bioavailability(86.44 vs 58.65%) significantly increased but $T_max(10\;vs\;20\;min)$ was significantly advanced. The current SEDDS containing IBP provide an alternative to improve an oral bio-availability of IBP.

• Journal of the Korean Chemical Society
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• v.50 no.6
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• pp.464-470
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• 2006

the coricosteroid drug dexamethasone is an efficacious antiinflammatory drug, it is difficult to formulate in an injectable formulation due to its poor aqueous solubility. A lipid-based nanosphere formulation containing dexamethasone was designed for solubilization of the drug in aqueous solution and sustained release of the drug from the nanosphere. The lipid nanospheres, composed of phospholipid, cholesterol and cationic lipid, were prepared by self emulsification-solvent diffusion method followed by diafiltration. Physicochemical characteristics such as mean particle diameter, zeta potential and drug loading efficiency of the lipid nanospheres were investigated according to the variation of either the kind of lipid or the lipid composition. The lipid nanospheres had a mean diameter 80-120 nm and dexamethasone loading efficiency of greater than 80%. The drug loading efficiency increased with the increase of the length of aliphatic chain attached to the phospholipid. However, the drug loading efficiency was inversely proportional to the increase of cholesterol content in the lipid composition. The lipid nanosphere could not be prepared without the use of cationic lipid and the drug loading efficiency was proportional to the increase of cationic lipid content. The lipid nanospheres containing dexamethasone are a promising novel drug carrier for an injectable formulation of the poorly water-soluble drugs.

• Journal of Powder Materials
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• v.30 no.4
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• pp.305-309
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• 2023

This study aims to prepare a colloidal silica-containing powder to enhance the solubility and dissolution rate of rivaroxaban using a self-nanoemulsifying drug delivery system (SNEDDS). We investigate the impact of colloidal silica on a nanoemulsion system for preparing powdered SNEDDS. The liquid SNEDDS comprises 30/20/50 (w/w/w) Peceol/Cremophor RH40/Tween 80, which results in the formation of the smallest droplets. Three powdered SNEDDS formulations are prepared by suspending the liquid SNEDDS formulation using colloidal silica and spray drying. The powdered SNEDDS prepared with liquid SNEDDS and colloidal silica at a ratio of 1/0.5 (w/w) exhibits the highest water solubility (0.94 ± 0.62 vs. 26.70 ± 1.81 ㎍/mL) and dissolution rate (38.4 ± 3.6 vs. 85.5 ± 3.4%, 45 min) when compared to the drug alone. Morphologically, the liquid SNEDDS is adsorbed onto colloidal silica and forms smaller particles. In conclusion, an SNEDDS containing rivaroxaban, prepared using colloidal silica, facilitates the creation of a nanoemulsion and enhances the water solubility of rivaroxaban. Accordingly, this technology holds significant potential for commercialization.

• Clean Technology
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• v.16 no.2
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• pp.80-87
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• 2010

In this study, micro- and submicron particles of itraconazole, a poorly water-soluble antifungal drug, were prepared for improving its aqueous solubility using an ultrasound-assisted supercritical fluid technique, called SAS-EM. The SAS-EM process used in our experiments was different from the conventional SAS-EM in that the ultrasound was applied directly to the spray nozzle. The effect of the ultrasonic power, temperature, and solvent on the formation of itraconazole particles were investigated. Smaller particles were obtained through our SAS-EM process compared with the ASES process, and the mean particle size decreased as the ultrasonic power increased. Our experimental results confirmed that the ultrasound-assisted supercritical fluid process is an efficient method for producing ultrafine particles.

• KSBB Journal
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• v.26 no.4
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• pp.283-292
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• 2011

Solid dispersion is one of well-established pharmaceutical techniques to improve the dissolution and consequent bioavailability of poorly water soluble drugs. It is defined as a dispersion of drug in an inert carrier matrix. Solid dispersions can be classified into three generations according to the carrier used in the system. First and second generations consist of crystalline and amorphous substances, respectively. Third generation carriers are surfactant, mixture of polymer and surfactants, and mixture of polymers. Solid dispersions can be generallyprepared by melting method and solvent method. While melting method requires high temperature to melt carrier and dissolve drug, solvent method utilizes solvent to dissolve the components. The improvement in dissolution through solid dispersions is attributed to reduction in drug particle size, improvement in wettability, and/or formation of amorphous state. The primary characteristics of solid dispersions, the presenceof drug in amorphous state, could be determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and fourier-transformed infrared spectroscopy (FTIR). In spite of the significant improvement in dissolution by solid dispersion technique, some drawbacks have limited the commercial application of solid dispersions. Thus, further studies should be conducted in a direction to improve the congeniality to commercialization.

• Journal of Pharmaceutical Investigation
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• v.41 no.4
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• pp.239-247
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• 2011

Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin has good permeability, but it also has low solubility (BCS class II), which reduces its bioavailability. To overcome this problem, a solid dispersion is formed using a spray-dryer with polymeric material carrier to potentially enhance the dissolution rate and extend drug absorption. As carriers for solid dispersion, Gelucire$^{(R)}$44/14 and Gelucire$^{(R)}$ 50/13 are semisolid excipients that greatly improve the bioavailability of poorly-soluble drugs. To avoid any toxic effects of an organic solvent, we used aqueous medium to melt Tween$^{(R)}$ 80 and distilled water. The structural behaviors of the raw materials and the solid dispersion were analyzed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and PXRD data indicated that the crystalline structure of simvastatin was transformed to an amorphous structure through solid dispersion. Then, solid dispersion-based tablets containing 20 mg simvastatin were prepared with excipients. Dissolution tests were performed in distilled water and artificial intestinal fluid using the USP paddle II method. Compared with that of the commercial tablet (Zocor$^{(R)}$ 20 mg), the release of simvastatin from solid dispersion based-tablet was more efficient. Although the stability study is not complete, this solid dispersion system is expected to deliver poorly water-soluble drugs with enhanced bioavailability and less toxicity.

• Bulletin of the Korean Chemical Society
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• v.32 no.5
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• pp.1587-1592
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• 2011

The aim of the present study was to improve the solubility and bioavailability of a poorly water-soluble drug in human body, using a solid dispersion technique (hot melt extrusion). The solid dispersion was prepared by cooling the hot melt of the drug in the carrier (Vitamin E TPGS and PVP). The dissolution rate of formulation 1 from a novel formulation prepared by solid dispersion technique was equal to release of formulation 6 (40% of eprosartan mesylate is in contrast to teveten$^{(R)}$) within 60 min (Table 1). The oral bioavailability of new eprosartan mesylate tablet having vitamin E TPGS and PVP K29 was tested on rats and dogs. Of the absorption enhancer and polymer tested, vitamin E TPGS and PVP K29, resulted in the greatest increases of AUC in animals (about 2.5-fold increase in rat and dog). When eprosartan mesylate was mixed with the absorption enhancer and polymer in a ratio of 2.94:2:1, vitamin E TPGS and PVP K29 improved eprosartan mesylate bioavailability significantly compared with the conventional immediate release (IR) tablet Teveten$^{(R)}$ (formulation 7). These results show that solid dispersion using vitamin E TPGS and PVP K29 is a promising approach for developing eprosartan mesylate drug products.

• KSBB Journal
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• v.26 no.3
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• pp.217-222
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• 2011

Itraconazole is a triazole antifungal agent to inhibit most fungal pathogens. To improve the oral absorption and dissolution of poorly water-soluble itraconazole, microsponge system composed of $Eudragit^{(R)}$ E100 and polyvinyl alcohol(PVA) formulated by quasi-emulsion solvent diffusion method, and its physicochemical properties and pharmacokinetic parameters of itraconazole were studied. The microsponge of itraconazole were discrete free flowing micro sized particles with perforated orange peel like morphology as visualized by scanning electron microscope (SEM). Results showed that the drug loading efficiency, production yield, and particle size of itraconazole microsponge were affected by drug to polymer ratio, the volume of internal phase containing methylene chloride, stirring rate and the concentration of PVA used. Also, the results showed that the dissolution rate of itraconazole from the microsponges was affected by drug to polymer ratio. In other words, the release rate of itraconazole from microsponges was increased from at least 27.43% to 64.72% after 2 h. The kinetics of dissolution mechanism showed that the dissolution data followed Korsmeyer-Peppas model. Therefore, these results suggest that microsponge system can be useful for the oral delivery of itraconazole by manipulating the release profile.

• Archives of Pharmacal Research
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• v.26 no.2
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• pp.173-181
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• 2003

A polymeric micelle drug delivery system was developed to enhance the solubility of poorly-water soluble drug, biphenyl dimethyl dicarboxylate, DDB. The block copolymers consisting of poly(D,L-lactide) (PLA) as the hydrophobic segment and methoxy poly(ethylene glycol) (mPEG) as the hydrophilic segment were synthesized and characterized by NMR, DSC and MALDI-TOF mass spectroscopy. The size of the polymeric micelles measured by dynamic light scattering showed a narrow monodisperse size distribution with the average diameter less than 50 nm. The MW of mPEG-PLA, 3000 (MW of mPEG, 2 K; MW of PLA, 1K), and the presence of hydrophilic and hydrophobic segments on the polymeric micelles were confirmed by MALDI-TOF mass spectroscopy and NMR, respectively. Polymeric micelle solutions of DDB were prepared by three different methods, i.e. the matrix method, emulsion method and dialysis method. In the matrix method, DDB solubility was reached to 13.29 mg/mL. The mPEG-PLA 2K-1K micelle system was compared with the poloxamer 407 micelle system for their critical micelle concentration, micelle size, solubilizing capacity, stability in dilution and physical state. DDB loaded-polymeric micelles prepared by the matrix method showed a significantly increased aqueous solubility (＞5000 fold over intrinsic solubility) and were found to be superior to the poloxamer 407 micelles as a drug carrier.

• Archives of Pharmacal Research
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• v.18 no.3
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• pp.183-188
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• 1995

Polymeric reinforcement and coatings of alginate beads were carried out to control the release rate of drug from alginate beads. A poorly water-soluble ibuprofen (IPF) was selected as a model drug. A commercially available $Eudragit^{\circledR}$ RS100 was also used as a polymer. Effects of polymeric contents, the presence of plasticizers and amount of drug loading on the release rate of drug were investigated. The release rate of drug from alginate beads in the simulated gastric fluid did not occur within 2 h but released immediately when dissolution media were switched to the simulated intestinal fluid. No significant difference of release rate from polymer-reinforced alginate bead without plasticizers was observed when compared to plain (simple) beads. However, the release rate of drug from polymer-reinforced alginate beads was further sustained and retarded when aluminium tristearate (AT) as a plasticizer was added to polymer. However, polyethylene glycol 400 (PEG400) did not change the release rate of drug from alginate beads although PEG400 was used to improve dispersion of polymer and sodium alginate, and plasticize $Eudragit^{\circledR}$ RS100 polymer. The presence of plasticizer was crucial to reinforce alginate gel matrices using a polymer. As the amount of drug loading increased, the release rate of drug increased as a result of decreasing effects of polymer contents in matrices. The significantly sustained release of drug from polymer-coated alginate beads occurred as the amount of polymer increased because the thickness of coated membrane increased so that cracks and pores of the outer surface of alginate beads could be reduced. The sustained and retarded action of polymer-reinforced and coated beads may result from the disturbance of swelling and erosion (disintegration) of alginate beads. From these findings, polymeric-reinforcement and coatings of alginate gel beads can provide an advanced delivery system by retarding the release rate of various drugs.