Prabagar Balakrishnan

Pusan National University, Pusan, Busan, South Korea

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Publications (25)80.57 Total impact

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    ABSTRACT: Abstract Context: Anti-inflammatory effect of advanced adipose stem cell derived protein extract (AAPE) could be improved by minimising protein degradation. Objective: To develop a proliposomal formulation of AAPE for the treatment of topical atopic dermatitis. Materials and methods: Proliposomal powder was manufactured by evaporating a solution of soy phosphatidyl choline, AAPE and Poloxamer 407 in ethanol under vacuum on sorbitol powder. Characterisation of proliposomes (zeta potential, diameter, stability and flowability) as well as in vivo efficacy in a dermatitis mouse model was investigated. Results and discussion: Reconstitution of the proliposomal powder formed liposomes of 589 ± 3.6 nm diameter with zeta potential of -51.33 ± 0.36 mV. Protein stability was maintained up to 90 days at 25 °C as proliposomes. In vivo studies on atopic dermatitis mouse model showed a significant reduction in IgE levels after topical AAPE proliposome treatment. Conclusion: AAPE proliposomes maintained protein stability and showed promising results for atopic dermatitis treatment.
    Journal of Microencapsulation 08/2014; · 1.57 Impact Factor
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    ABSTRACT: The intention of this study was to compare the physicochemical properties, stability and bioavailability of a clopidogrel napadisilate (CN)-loaded solid dispersion (SD) and solid self-microemulsifying drug delivery system (solid SMEDDS). SD was prepared by a surface attached method using different ratios of Cremophor RH60 (surfactant) and HPMC (polymer), optimized based on their drug solubility. Liquid SMEDDS was composed of oil (peceol), a surfactant (Cremophor RH60) and a co-surfactant (Transcutol HP). A pseudo-ternary phase diagram was constructed to identify the emulsifying domain, and the optimized liquid SMEDDS was spray dried with an inert solid carrier (silicon dioxide), producing the solid SMEDDS. The physicochemical properties, solubility, dissolution, stability and pharmacokinetics were assessed and compared to clopidogrel napadisilate (CN) and bisulfate (CB) powders. In solid SMEDDS, liquid SMEDDS was absorbed or coated inside the pores of silicon dioxide. In SD, hydrophilic polymer and surfactants were adhered onto drug surface. The drug was in crystalline and molecularly dispersed form in SD and solid SMEDDS, respectively. Solid SMEDDS and SD greatly increased the solubility of CN but gave lower drug solubility compared to CB powder. These preparations significantly improved the dissolution of CN, but the latter more increased than the former. Stability under accelerated condition showed that they were more stable compared to CB powder, and SD was more stable than solid SMEDDS. They significantly increased the oral bioavailability of CN powder. Furthermore, SD showed significantly improved oral bioavailability compared to solid SMEDDS and CB powder. Thus, SD with excellent stability and bioavailability is recommended as an alternative for the clopidogrel-based oral formulation.
    Carbohydrate Polymers 01/2014; 114:365–374. · 3.48 Impact Factor
  • Min-Jeong Park, Prabagar Balakrishnan, Su-Geun Yang
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    ABSTRACT: Self-microemulsifying drug delivery system (SEDDS) cored-polymeric nanocapsules (NC) were fabricated using emulsion diffusion method for the controlled oral absorption of the poorly water soluble drug, cyclosporine. Poly-DL-lactide (PDLLA) was used as the shell-forming polymer. The NCs in different polymer/oil ratios (from 25/125 to 125/125) were prepared following a solvent-diffusion method. Especially, the SEDDS oil-core compositions, which can form microemulsions on dispersion, were selected based on a pseudo-phase diagram study and further optimized based on the solubility and permeability studies. The prepared NCs were with a mean diameter of 150∼220nm and 9.4∼4.5% w/w drug loading. In vivo study in rats showed that the optimized NC(50/125) and NC(100/125) released the drug in controlled way as well as enhanced the bioavailability significantly with AUC(0-24h) values of 14880.3±1470.6 and 12657.8±754.5 ng·h/ml, respectively, compared to that of SEDDS-core solution (9878.9±409.6 ng·h/ml). Moreover it was observed that the NCs maintained blood concentration of cyclosporine (>500ng/ml) for 14 to 20h but in the case of control formulation it was only 7.33h. Our results suggest that the prepared NCs could be a potential carrier for the oral controlled release formulation of cyclosporine.
    International Journal of Pharmaceutics 10/2012; · 3.99 Impact Factor
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    ABSTRACT: A new lipid nanoemulsion (LNE) system containing granisetron (GRN) was developed and its in vitro permeation-enhancing effect was evaluated using Caco-2 cell monolayers. Particle size, polydispersity index (PI) and stability of the prepared GRN-loaded LNE systems were also characterized. The mean diameters of prepared LNEs were around 50nm with PI<0.2. Developed LNEs were stable at 4°C in the dark place over a period of 12 weeks. In vitro drug dissolution and cytotoxicity studies of GRN-loaded LNEs were performed. GRN-loaded LNEs exhibited significantly higher drug dissolution than GRN suspension at pH 6.8 for 2h (P<0.05). In vitro permeation study in Caco-2 cell monolayers showed that the LNEs significantly enhanced the drug permeation compared to GRN powder. The in vivo toxicity study in the rat jejunum revealed that the prepared GRN-loaded LNE was as safe as the commercial formulation (Kytril). These results suggest that LNE could be used as a potential oral liquid formulation of GRN for anti-emetic treatment on the post-operative and chemotherapeutic patients.
    Colloids and surfaces B: Biointerfaces 07/2012; 101C:475-480. · 3.55 Impact Factor
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    ABSTRACT: To study the effect of β-cyclodextrin (βCD) inclusion complex on the bioavailability of clotrimazole from poloxamer-based suppository, formulations composed of P 188, propylene glycol and different molar ratio of clotrimazole-βCD inclusion complex were prepared. Clotrimazole (1%) has been formulated in a suppository using the thermo sensitive polymer P188 (70%) together with propylene glycol (30%). To increase its aqueous solubility, clotrimazole was incorporated as its inclusion complex at various molar ratios with βCD (1:0.25, 1:0.5, 1:1, and 1:2). The inclusion complex was characterized by differential scanning calorimetry (DSC), XRD and phase solubility studies. It was observed that the complexation with βCD, particularly at high molar ratio (F3 (1:1) and F4 (1:2)) decreased the release profile of clotrimazole considerably. However, suppositories containing inclusion complex at low molar ratio (F1 (1:0.25) and F2 (1:0.5)) showed excellent release profile compared to control formulation. In vivo study in rats at 15 mg/Kg dose showed that the F1 and F2 (82.39 ± 15.40 and 67.05 ± 8.79, respectively) significantly increased the AUC compared to that of F3 (41.48 ± 11.51), F4 (23.34 ± 8.37) and control (46.7 ± 7.87) suppositories. Thus, the suppositories containing inclusion complexes prepared at low drug to βCD molar ratio (F1) could be a potential suppository formulation to increase the bioavailability of hydrophobic drugs such as clotrimazole.
    Archives of Pharmacal Research 07/2012; 35(7):1169-75. · 1.54 Impact Factor
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    ABSTRACT: This study describes a novel carrier, transethosome, for enhanced skin delivery of voriconazole. Transethosomes (TELs) are composed of phospholipid, ethanol, water and edge activator (surfactants) or permeation enhancer (oleic acid). Characterization of the TELs was based on results from recovery, particle size, transmission electron microscopy (TEM), zeta potential and elasticity studies. In addition, skin permeation profile was obtained using static vertical diffusion Franz cells and hairless mouse skin treated with TELs containing 0.3% (w/w) voriconazole, and compared with those of ethosomes (ELs), deformable liposomes (DLs), conventional liposomes (CLs) and control (polyethylene glycol, PG) solutions. The recovery of the studied vesicles was above 90% in all vesicles, as all of them contained ethanol (7-30%). There was no significant difference in the particles size of all vesicles. The TEM study revealed that the TELs were in irregular spherical shape, implying higher fluidity due to perturbed lipid bilayer compared to that of other vesicles which were of spherical shape. The zeta potential of vesicles containing sodium taurocholate or oleic acid showed higher negative value compared to other vesicles. The elasticities of ELs and TELs were much higher than that of CLs and DLs. Moreover, TELs dramatically enhanced the skin permeation of voriconazole compared to the control and other vesicles (p<0.05). Moreover, the TELs enhanced both in vitro and in vivo skin deposition of voriconazole in the dermis/epidermis region compared to DLs, CLs and control. Therefore, based on the current study, the novel carrier TELs could serve as an effective dermal delivery for voriconazole.
    Colloids and surfaces B: Biointerfaces 12/2011; 92:299-304. · 3.55 Impact Factor
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    ABSTRACT: A flexible porous three-dimensional (3D) matrix of hyaluronic acid (HA) was developed to improve the rigidity problems of the previously developed 3D systems. The viscoelasticity of the new formulation was expected to facilitate the differentiation of chondrocytes for the treatment of osteoarthritis (OA). The 3D matrix was fabricated using poly (ethylene glycol) diglycidyl ether (PEGDG) as a cross-linker, which was identified by Fourier transform infrared spectroscopy (FT-IR). The porous structure of the matrix was observed by scanning electron microscopy (SEM). The rheological characteristics of the fabricated HA matrix, that transforms to a gel-like semisolid state in the culture media with and without chondrocytes, were investigated. The proliferation of chondrocytes in the matrix increased according to the cultivation time. The chondrogenic differentiation of chondrocytes in the matrix also increased as determined by reverse transcription-polymerase chain reaction (RT-PCR) and by quantification of sulfated glycosaminoglycan (s-GAG). Moreover, safranin-O staining demonstrated that chondrocytes in the matrix produced extracellular matrix (ECM) after 28 days of culture. Thus, these results show that the "flexible" porous 3D cell delivery system based on HA could improve the clinical efficiency in OA treatment.
    Colloids and surfaces B: Biointerfaces 11/2011; 91:106-13. · 3.55 Impact Factor
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    ABSTRACT: In this study, porous sodium hyaluronic acid/sodium alginate (HA/SA) scaffold based on interpenetrating polymeric network (IPN) technique has been fabricated, where HA and SA were cross-linked with poly(ethylene glycol) diglycidyl ether (PEGDG) and calcium chloride, respectively. The mean pore size and the swelling ratio of fabricated scaffolds decreased, and the compressive strength increased as the content of SA increased in HA/SA IPN scaffold. Rabbit chondrocytes were seeded within the HA/SA IPN scaffolds, and then their proliferation as well as chondrogenic differentiation was examined. DNA contents observed from the chondrocytes cultured in the IPN scaffolds increased with time over 21 days, which demonstrated that the rabbit chondrocytes continued to proliferate in HA/SA scaffolds. Results of the 1,9-dimethylmethylene blue (DMMB) and p-dimethylaminobenzaldehyde (DMBA) assays showed that glycosaminoglycan (s-GAG) and collagen contents increased over culture period, indicating the chondrogenic differentiation in the scaffold. Reverse transcription-polymerase chain reaction (RT-PCR) results showed the expression of type II collagen, the main chondrogenic differentiation marker. The bands indicating mRNA expression of type II collagen increased with the culture period. These results demonstrated that the porous HA/SA IPN scaffolds were successfully prepared and could serve as an effective delivery system of the three-dimensional culture of chondrocytes.
    Colloids and surfaces B: Biointerfaces 08/2011; 88(2):711-6. · 3.55 Impact Factor
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    ABSTRACT: Biocompatible microparticles prepared by lyophilization were developed for intranasal protein delivery. To test for the feasibility of this formulation, stability of the incorporated protein and enhancement of in vitro permeation across the nasal epithelium were evaluated. Lyophilization was processed with hydroxypropylmethylcellulose (HPMC) or water soluble chitosan (WCS) as biocompatible polymers, hydroxypropyl-β-cyclodextrin (HP-β-CD) and d-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS 1000) as permeation enhancers, sugars as cryoprotectants and lysozyme as the model protein. As a result, microparticles ranging from 6 to 12μm were developed where the maintenance of the protein conformation was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism and fluorescence intensity detection. Moreover, in vitro bioassay showed that the lysozyme activity was preserved during the preparation process while exhibiting less cytotoxicity in primary human nasal epithelial (HNE) cells. Results of the in vitro release study revealed slower release rate in these microparticles compared to that of the lysozyme itself. On the other hand, the in vitro permeation study exhibited a 9-fold increase in absorption of lysozyme when prepared in lyophilized microparticles with HPMC, HP-β-CD and TPGS 1000 (F4-2). These microparticles could serve as efficient intranasal delivery systems for therapeutic proteins.
    International Journal of Pharmaceutics 06/2011; 416(1):77-84. · 3.99 Impact Factor
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    ABSTRACT: The objectives of this study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine (PC), an endogenous phospholipid with excellent in vivo solubilization capacity, as oil phase for the delivery of bioactive carotenoid lutein, by spray drying the SNEDDS (liquid system) containing PC using colloidal silica (Aerosil® 200 VV Pharma) as the inert solid carrier, and to evaluate the enhanced bioavailability (BA) of lutein from S-SNEDDS. The droplet size analyses revealed droplet size of less than 100 nm. The solid state characterization of S-SNEDDS by SEM, DSC, and XRPD revealed the absence of crystalline lutein in the S-SNEDDS. The bioavailability study performed in rabbits resulted in enhanced values of C(max) and AUC for S-SNEDDS. The enhancement of C(max) for S-SNEDDS was about 21-folds and 8-folds compared with lutein powder (LP) and commercial product (CP), respectively. The relative BA of S-SNEDDS compared with CP or LP was 2.74-folds or 11.79-folds, respectively. These results demonstrated excellent ability of S-SNEDDS containing PC as oil phase to enhance the BA of lutein in rabbits. Thus, S-SNEDDS containing PC as oil phase could be a useful lipid drug delivery system for enhancing the BA of lutein in vivo.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 04/2011; 79(2):250-7. · 3.15 Impact Factor
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    ABSTRACT: To enhance permeation and solubility of an intranasal delivery system of fexofenadine hydrochloride (FXD HCl), a new formulation using poloxamer 407 (P407)/hydroxypropyl-β-cyclodextrin (HP-β-CD)-based thermoreversible gels with chitosan, was developed. Prepared gels were characterized by gelation temperature, viscosity, viscoelasticity, and drug release profile. The in vitro permeation study was performed in primary human nasal epithelial cell monolayers cultured by air-liquid interface method. The addition of chitosan caused the slight elevation of gelation temperature and viscosity-enhancing effect. Viscosity enhancement by the incorporation of chitosan caused the retardation of drug release from P407 gels in in vitro release test. The in vitro permeation profile showed that the increase in chitosan content (0.1% and 0.3%, w/v) significantly enhanced the permeation of FXD HCl. After intranasal administration of P407/HP-β-CD-based thermoreversible gels containing 0.1% and 0.3% of chitosan in rabbits at 0.5 mg/kg dose, plasma concentrations of FXD HCl were significantly higher than those of nasal solutions (p < 0.05). In particular, the bioavailability of the optimized thermoreversible gel containing 0.3% chitosan was about 18-fold higher than that of the solution type. These results suggested the feasibility that thermosensitive gels could be used as an effective dosage form to enhance the nasal absorption of FXD HCl.
    Journal of Pharmaceutical Sciences 02/2011; 100(2):681-91. · 3.13 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the physicochemical properties and in vitro evaluation of fatty ester prodrugs of salicylic acid for ultraviolet (UV) protection. The physicochemical properties such as lipophilicity, chemical stability and enzymatic hydrolysis were investigated with the following fatty ester prodrugs of salicylic acid: octanoyl (C8SA), nonanoyl (C9SA), decanoyl (C10SA), lauroyl (C12SA), myristoyl (C14SA) and palmitoyl oxysalicylate (C16SA). Furthermore, their skin permeation and accumulation were evaluated using a combination of common permeation enhancing techniques such as the use of a lipophilic receptor solution, removal of stratum corneum and delipidization of skin. Their k' values were proportional to the degree of carbon-carbon saturation in the side chain. All these fatty esters were highly stable in 2-propanol, acetonitrile and glycerin, but unstable in methanol and ethanol. They were relatively unstable in liver and skin homogenates. In particular, C16SA was mostly hydrolyzed to its parent compound in hairless mouse liver and skin homogenates, suggesting that it might be converted to salicylic acid after its topical administration. In the skin permeation and accumulation study, C16SA showed the poorest permeation in all skins, suggesting that it could not be permeated in the skin. Furthermore, C14SA and C16SA were less accumulated in delipidized skin compared with normal skin or stripped skin, suggesting that these esters had relatively strong affinities for lipids compared with the other prodrugs in the skin. C16SA showed significantly higher dermal accumulation in all skins compared with its parent salicylic acid. Thus, the palmitoyl oxysalicylate (C16SA) might be a potential candidate for UV protection due to its absence of skin permeation, smaller uptake in the lipid phase and relatively lower skin accumulation.
    Drug Development and Industrial Pharmacy 01/2011; 37(7):841-8. · 1.54 Impact Factor
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    ABSTRACT: The aim of this study was to prepare microparticles (MPs) of granisetron (GRN) in combination with hydroxypropyl-β-cyclodextrin (HP-β-CD) and sodium carboxymethylcellulose (CMC-Na) by the simple freeze-drying method for intranasal delivery. The composition of MPs was determined from the phase-solubility study of GRN in various CDs. Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD) analysis and differential scanning calorimetry (DSC) studies were performed to evaluate possible interactions between GRN and excipients. The results indicated the formation of inclusion complex between GRN and CD, and the conversion of drug into amorphous state. The in vitro release of GRN from MPs was determined in phosphate buffered saline (pH 6.4) at 37°C. Cytotoxicity of the MPs and in vitro permeation study were conducted by using primary human nasal epithelial (HNE) cells and their monolayer system cultured by air-liquid interface (ALI) method, respectively. The MPs showed significantly higher GRN release profile compared to pure GRN. Moreover, the prepared MPs showed significantly lower cytotoxicity and higher permeation profile than that of GRN powder (p<0.05). These results suggested that the MPs composed of GRN, HP-β-CD and CMC-Na represent a simple and new GRN intranasal delivery system as an alternative to the oral and intravenous administration of GRN.
    International Journal of Pharmaceutics 11/2010; 400(1-2):59-65. · 3.99 Impact Factor
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    ABSTRACT: A Shirasu-porous-glass (SPG) membrane with a mean pore size of 2.5 μm was used to produce an oil/water (O/W) nanoemulsion of flurbiprofen consisting of methylene chloride as the dispersed phase, polyvinyl alcohol (PVA) as the stabilizer and a mixture of Tween 20 and Tween 80 in demineralized water as the continuous phase. Emulsion droplets with a mean droplet size of 25 times smaller than the mean pore size and a narrow droplet size distribution were produced using 5% emulsifier at a feed pressure of 15 kPa. Under these conditions the z-average diameter and size distribution of the emulsion droplets formed were influenced by the type of surfactant, agitator speed (150-1200 rpm), feed pressure (15-80 kPa), stabilizer concentration (0-4, w/v) and the temperature of the continuous phase. Increasing the agitator speed and stabilizer concentration increased the z-average diameter and decreased the size uniformity. There was a linear relationship between the increased feed pressure and the decreased z-average diameter of the emulsion droplets. However, the uniformity of the size distribution decreased with increasing feed pressure. The continuous phase temperature played an important role in particle size and distribution. The nanoemulsion composed of oil, water, PVA and the surfactant mixture at the weight ratio of 10/100/1/5 was prepared using a SPG membrane at an agitator speed of 300 rpm, a feed pressure of 15 kPa and a continuous phase temperature of 25 °C. Our results indicated that these conditions led to relatively uniform emulsion droplets with a narrow size distribution and high zeta potential. This emulsion was stable for at least 13 h. Furthermore, the droplets in the emulsion containing the drug were not smaller but were more uniform with a narrower distribution compared to those without the drug.
    International Journal of Pharmaceutics 11/2010; 404(1-2):191-7. · 3.99 Impact Factor
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    ABSTRACT: To develop a novel sibutramine base-loaded solid dispersion with enhanced solubility and bioavailability, various solid dispersions were prepared using a spray drying technique with hydrophilic polymers such as gelatin, HPMC and citric acid. Their solubility, thermal characteristics and crystallinity were investigated. The dissolution and pharmacokinetics of the sibutramine base-loaded solid dispersion were then compared with a sibutramine hydrochloride monohydrate-loaded commercial product (Reductil). The solid dispersions prepared with gelatin gave higher drug solubility than those prepared without gelatin, irrespective of the amount of polymer. The sibutramine base-loaded solid dispersions containing hydrophilic polymer and citric acid showed higher drug solubility compared to sibutramine base and sibutramine hydrochloride monohydrate. Among the formulations tested, the solid dispersion composed of sibutramine base/gelatin/HPMC/citric acid at the weight ratio of 1/0.8/0.2/0.5 gave the highest solubility of 5.03+/-0.24 mg/ml. Our DSC and powder X-ray diffraction results showed that the drug was present in an altered amorphous form in this solid dispersion. The difference factor (f(1)) values between solid dispersion and commercial product were 2.82, 6.65 and 6.31 at pH 1.2, 4.0 and 6.8, respectively. Furthermore, they had the similarity factor (f(2)) value of 65.68, 53.43 and 58.97 at pH 1.2, 4.0 and 6.8, respectively. Our results suggested that the solid dispersion and commercial product produced a similar correlation of dissolution profiles at all pH ranges. The AUC, C(max) and T(max) of the parent drug and metabolite I and II from the solid dispersion were not significantly different from those of the commercial product, suggesting that the solid dispersion might be bioequivalent to the commercial product in beagle dogs. Thus, the sibutramine base-loaded solid dispersion prepared with gelatin, HPMC and citric acid is a promising candidate for improving the solubility and bioavailability of the poorly water-soluble sibutramine base.
    International Journal of Pharmaceutics 09/2010; 397(1-2):225-30. · 3.99 Impact Factor
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    ABSTRACT: To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats. A single isotropic region was found in the pseudo-ternary phase diagrams developed at various ratios with Lauroglycol 90 as oil, Labrasol as surfactant and Plurol Oleique CC49 or its mixture with PEG-400 (1:1) as cosurfactant. An increase in the microemulsion region in pseudo-ternary phase systems was observed with increased surfactant concentration. The optimized microemulsion formulations showed higher solubulization of fexofenadine, i.e., F1 (22.64 mg/mL) and F2 (22.98 mg/mL), compared to its intrinsic water solubility (1.51 mg/mL). Nasal absorption of fexofenadine from these microemulsions was found to be fairly rapid. Tmax was observed within 5 min after intranasal administration at 1.0 mg/kg dose, and the absolute bioavailability (0-4 h) was about 68% compared to the intravenous administration in rats. Our results suggested that these microemulsion formulations could be used as an effective intranasal dosage form for the rapid-onset delivery of fexofenadine
    International Journal of Pharmaceutics 08/2010; 395(1-2):309-16. · 3.99 Impact Factor
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    ABSTRACT: To develop an industrially practical thermosensitive injectable hydrogel that is easy to administer, gels quickly in the body and allows sustained release of the drug, poloxamer-based hydrogels containing piroxicam as a model drug were prepared with poloxamer, sodium hydroxide and sodium chloride using the cold method. Their rheological characterization, dissolution and pharmacokinetics after intramuscular administration to rabbits were evaluated. Among the ingredients tested, sodium hydroxide and piroxicam decreased the viscosity and retarded the gelation time of the injectable gel. However, sodium chloride did the opposite. The thermosensitive injectable gel composed of 2.5% piroxicam, 15% P 407, 17% P 188, 0.01% sodium hydroxide and 1.6% sodium chloride was instantly applied to practical industrial product, since it was easy to administer intramuscularly and gelled quickly in the body. The drug was dissolved out of the hydrogels by Fickian diffusion through the extramicellar aqueous channels of the gel matrix. Sodium chloride barely affected the dissolution mechanism or dissolution rate of the drug from the injectable gels. Furthermore, it maintained the plasma concentrations of drug for 4 days and gave a 150-fold higher AUC compared to piroxicam solution. Thus, it would be practically useful for delivering piroxicam in a pattern that allows sustained release for a long time, leading to better bioavailability.
    International Journal of Pharmaceutics 08/2010; 395(1-2):317-23. · 3.99 Impact Factor
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    ABSTRACT: To develop a novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability, various itraconazole-loaded solid dispersions were prepared with water, polyvinylpyrroline, poloxamer and citric acid. The effect of carriers on aqueous solubility of itraconazole was investigated. Their physicochemical properties were investigated using SEM, DSC, and powder X-ray diffraction. The dissolution, bioavailability in rats and stability of solid dispersions were evaluated. Unlike conventional solid dispersion system, the itraconazole-loaded solid dispersion with relatively rough surface did not change crystalline form of drug. Our DSC and powder X-ray diffraction results suggested that this solid dispersion was formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting in conversion of the hydrophobic drug to hydrophilic form. The itraconazole-loaded solid dispersion at the weight ratio of itraconazole/polyvinylpyrroline/poloxamer of 10/2/0.5 gave maximum drug solubility of about 20 microg/mL. It did not change the crystalline form of drug for at least 6 months, indicating that it was physically stable. It gave higher AUC, C(max) and T(max) compared to itraconazole powder and similar values to the commercial product, suggesting that it was bioequivalent to commercial product in rats. Thus, it would be useful to deliver a poorly water-soluble itraconazole without crystalline change with improved bioavailability.
    Archives of Pharmacal Research 08/2010; 33(8):1217-25. · 1.54 Impact Factor
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    ABSTRACT: A mixed micelle that comprised of MPEG-PLA (MPP) and Pluronic copolymers was developed for enhanced bioavailability and to overcome multidrug resistance of docetaxel in cancer therapy. The mixed micelles that sufficiently solubilized docetaxel were evaluated for the effect of Pluronic copolymers weight ratio on the mixed micelles with respect to drug loading and drug release. In vitro, cell viability and cytotoxicity studies in KB and KBv cells revealed that the mixed micellar formulations were more potent than the commercial docetaxel formulation (Taxotere). In vivo pharmacokinetics study in rats showed that the mixed micelles significantly enhanced the bioavailability of docetaxel (3.6 fold) than Taxotere. Moreover, antitumor activity assessed in KBv cancer xenograft BALB/C nude mice models showed that the mixed micelles significantly reduced the tumor size than the control (Taxotere). Clear differences in the intracellular uptake of docetaxel between MPP and mixed micelles were observed using confocal laser scanning microscopy. This study presents not only a new micelle structure for a diblock-triblock copolymer system, but also a method for enhanced bioavailability of docetaxel and to overcome some of the limitations on its multidrug resistance in cancer therapy.
    Biomaterials 03/2010; 31(8):2371-9. · 8.31 Impact Factor
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    ABSTRACT: Self-nanoemulsifying drug delivery system (SNEDDS) containing oil (Phosal 53 MCT), surfactant (Labrasol), and cosurfactant (Transcutol-HP or Lutrol-E400) was prepared to enhance solubility and dissolution of lutein. Ternary phase diagram of the SNEDDS was constructed to identify the self-emulsifying regions following which the percentage of oil, surfactant, and cosurfactant in the SNEDDS were optimized in terms of emulsification time and mean emulsion droplet size. The optimized SNEDDS consists of 25% oil, 60% surfactant, and 15% cosurfactant. When measured using USP XXIII dissolution apparatus II, the emulsification time of the SNEDDS prepared with Transcutol-HP as cosurfactant was less than 20 sec, and it was 20-30 sec in the SNEDDS prepared with Lutrol-E400. Mean emulsion droplet size was slightly smaller when Transcutol-HP was used as cosurfactant (80 +/- 6 nm), compared to when Lutrol- E400 was used (93 +/- 6 nm). Dissolution of lutein from the solid SNEDDS (physical mixture of the optimized SNEDDS and Aerosil 200) took place immediately (less than 5 min) in distilled water, and, once dissolved, no precipitation or aggregation of the drug were observed. In contrast, no drug was released from lutein powder or from the commercial product (Eyelac(R)) until 3 h of the study duration.
    Archives of Pharmacal Research 03/2010; 33(3):417-26. · 1.54 Impact Factor

Publication Stats

310 Citations
80.57 Total Impact Points

Institutions

  • 2012
    • Pusan National University
      • College of Pharmacy
      Pusan, Busan, South Korea
  • 2010–2012
    • Seoul National University
      • Research Institute of Pharmaceutical Sciences
      Sŏul, Seoul, South Korea
    • Shenyang Pharmaceutical University
      • College of Pharmacy
      Feng-t’ien, Liaoning, China
  • 2009–2012
    • Yeungnam University
      • College of Pharmacy
      Asan, South Chungcheong, South Korea