Ming-Thau Sheu - Academia.edu (original) (raw)

Papers by Ming-Thau Sheu

International Journal of Nanomedicine, 2016

Quercetin (Que) is known to have biological benefits including an anticancer effect, but low wate... more Quercetin (Que) is known to have biological benefits including an anticancer effect, but low water solubility limits its clinical application. The aim of this study was to develop a lecithin-based mixed polymeric micelle (LMPM) delivery system to improve the solubility and bioavailability of Que. The optimal Que-LMPM, composed of Que, lecithin, Pluronic(®) P123, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy[poly(ethylene glycol)-2000] in a proportion of 3:1:17.5:2.5 (w/w), was prepared by a thin-film method. The average size, polydispersion index, encapsulating efficiency, and drug loading of Que-LMPM were 61.60±5.02 nm, 0.589±0.198, 96.87%±9.04%, and 12.18%±1.11%, respectively. The solubility of Que in the Que-LMPM system increased to 5.81 mg/mL, compared to that of free Que in water of 0.17-7.7 μg/mL. The Que-LMPM system presented a sustained-release property in vitro. The in vitro cytotoxicity assay showed that the 50% inhibitory concentration values toward MCF-7 breast cancer cells for free Que, blank LMPMs, and Que-LMPMs were >200, >200, and 110 μM, respectively, indicating the nontoxicity of the LMPM carrier, but the LMPM formulation enhanced the cytotoxicity of Que against MCF-7 cells. A cellular uptake assay also confirmed the intake of Que-LMPM by MCF-7 cells. An in vivo pharmacokinetic study demonstrated that Que-LMPMs had higher area under the concentration-time curve and a longer half-life, leading to better bioavailability compared to a free Que injection. Due to their nanosize, core-shell structure, and solubilization potential, LMPMs were successfully developed as a drug delivery system for Que to improve its solubility and bioavailability.

Journal of pharmaceutical sciences, Jan 14, 2016

The aim of the present study was to prepare sublingual delivery systems for sildenafil and evalua... more The aim of the present study was to prepare sublingual delivery systems for sildenafil and evaluate its relative bioavailability after sublingual administration in rabbits to attain a rapid onset of action with good efficacy at lower doses. For sublingual application, sildenafil and its citrate were formulated in 2 different dosage forms: the first was a sublingual spray consisting of sildenafil in 2 microemulsion systems, oleic acid or propylene glycol (PG), and the second was sublingual tablets prepared with various granulated sublingual sprays adsorbed onto a silicate adsorbant (Florite(®) R), binders (Cyclocel(®) or EMDEX(®)), and disintegrants (Ac-Di-Sol(®) or Kollidon(®) CL). Results showed that sublingual absorption of sildenafil spray prepared with PG was fairly rapid. At a 0.5-mg dose, the mean onset of action was 1.3 ± 0.6 min and lasted for about 1.5 h according to the pharmacokinetic studies. In vivo studies also showed that for sublingual tablets formulated with sildena...

Colloids and surfaces. B, Biointerfaces, Jan 18, 2016

Doxorubicin (DOX) thermosensitive hydrogels (TSHs) incorporated with docetaxel (DOC)-loaded mixed... more Doxorubicin (DOX) thermosensitive hydrogels (TSHs) incorporated with docetaxel (DOC)-loaded mixed micelles were developed to co-deliver these two drugs through a TSH system, DH700kMF-13.5/M-DocLF, to improve local cancer therapy and reduce side effects. First, Pluronics-based DOC-loaded mixed micelles were developed and optimized. The optimal formulation designated as M-DocLF was composed of 1mg/g docetaxel, 15mg/g Pluronic F127 (PF127), and 45mg/g Pluronic L121 (PL121). Rheological tests showed that DH700kMF-13.5/M-DocLF was an injectable flowing solution, which formed a nonflowing gel at body temperature. After intratumoral (IT) or peritumoral (PT) administration, DH700kMF-13.5/M-DocLF demonstrated efficient growth inhibition of CT-26 tumors in a Balb/c mice model. The tumor inhibitory rate after IT administration of DH700kMF-13.5/M-DocLF was 92.4%, followed by 85.8%, 75.6%, 62.9%, 50.6%, and 49.5% for DH700kMF-15, free DOX, F-13.5/M-DocLF, Tynen (DOC solution), and M-DocLF, respe...

PloS one, 2016

There has been considerable interest in the biological functions of astaxanthin and its potential... more There has been considerable interest in the biological functions of astaxanthin and its potential applications in the nutraceutical, cosmetics, food, and feed industries in recent years. However, the unstable structure of astaxanthin considerably limits its application. Therefore, this study reports the encapsulation of astaxanthin in calcium alginate beads using the extrusion method to improve its stability. This study also evaluates the stability of the encapsulated astaxanthin under different storage conditions. The evaluation of astaxanthin stability under various environmental factors reveals that temperature is the most influential environmental factor in astaxanthin degradation. Stability analysis shows that, regardless of the formulation used, the content of astaxanthin encapsulated in alginate beads remains above 90% of the original amount after 21 days of storage at 25°C. These results suggest that the proposed technique is a promising way to enhance the stability of other...

International journal of nanomedicine, 2015

To alleviate the inherent problems of amphotericin B (AmB), such as poor water solubility and nep... more To alleviate the inherent problems of amphotericin B (AmB), such as poor water solubility and nephrotoxicity, a novel self-assembling mixed polymeric micelle delivery system based on lecithin and combined with amphiphilic polymers, Pluronic(®), Kolliphor(®), d-alpha tocopheryl polyethylene glycol succinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(poly(ethylene glycol)-2000 (DSPE-PEG2K) was developed. An optimal formulation (Ambicelles) composed of AmB:lecithin:DSPE-PEG2K in a 1:1:10 weight ratio was obtained. The particle size, polydispersion index, drug encapsulation efficiency, and drug loading were 187.20±10.55 nm, 0.51±0.017, 90.14%, and 7.51%, respectively, and the solubility was increased from 0.001 to 5 mg/mL. Compared with that of Fungizone(®), the bioavailability of Ambicelles administered intravenously and orally increased 2.18- and 1.50-fold, respectively. Regarding the in vitro cytotoxicity, Ambicelles had a higher cell viability than free AmB solut...

Purpose: To obtain a synergy between the swelling indexes of swellable polymers with a combinatio... more Purpose: To obtain a synergy between the swelling indexes of swellable polymers with a combination of several swelling functionalities in the unit, the investigation of different types of swellable polymers and addition of an ionic complex of polyelectrolytes with regard to the swelling behavior was conducted in this study. Methods: Physical characterizations of the tablets, including a swelling index based on weight variation and visual swelling observations, were carried out. Results: Of the four different grades of HEC 250 examined (H, HX, HHX and M), HEC 250HHX exhibited the greatest swelling index. Lower molecular weight PEO, varying from Mw 00K to Mw 900K, exhibited a low swelling index and dissolved almost completely after immersion for 2 to 4 h in the medium. However, the swelling ability of PEO (Mw 8,000K) was found to be sustainable to an extent greater than that for HEC 250HHX. Combination of a lower molecular weight PEO (Mw 900K) with HEC 250HHX resulted in a lower swelling index than that for HEC 250HHX alone, whereas a high molecular weight PEO (Mw 8,000K) incorporated with HEC 250HHX resulted in a higher swelling rate. However, the addition of an ionic complex of polyelectrolytes produced only a slight improvement in swelling index. Conclusion: HEC exhibited a suitable swelling index apart from the higher molecular weight PEO (Mw 8,000K). The addition of 50% Carbopol in HEC would be preferable to increase the swelling of the tablet. The swelling index obtained from the formulation with 0% to 50% of chitosan showed a good swelling index in the pH .2 media, but the degree of swelling size was not high enough as required.

Journal of parenteral science and technology: a publication of the Parenteral Drug Association

In this study, fibrin beads containing macromolecules of different molecular weight were prepared... more In this study, fibrin beads containing macromolecules of different molecular weight were prepared in two different size distributions by varying the ratio of oleic acid to mineral oil in the oil phase of the emulsion system. The release characteristics were examined and compared. A dependence on the size of the fibrin microspheres for macromolecule release from fibrin microspheres was demonstrated: the smaller the size of the fibrin microspheres, the faster the release rate of the macromolecules. In addition, the apparent diffusion coefficient was found to be a function of the molecular size of the macromolecules. As a result, the larger the molecular weight of the macromolecules, the smaller the apparent diffusion coefficient. However, the release of lysozyme and insulin dissolved in 0.1 N HCI solution was undetectable.

Drug design and delivery

Glutaraldehyde treatment of dexamethasone-containing cylindrical fibrin gels (obtained by the thr... more Glutaraldehyde treatment of dexamethasone-containing cylindrical fibrin gels (obtained by the thrombin-induced polymerization of fibrinogen in the presence of the drug) causes cross-linking of the gels and modification of the pore structure. The effect on the release of dexamethasone was assessed by measuring the diffusion coefficient of the drug across treated and untreated gels; diffusion across the treated gels was significantly decreased as compared with untreated gels, but was little affected by the concentration of glutaraldehyde used in the treatment. In biodegradable tests, the treated gels (all concentrations of glutaraldehyde) were resistant to digestion even in the presence of plasmin, but untreated gels were digested, and the digestion rate was accelerated by plasmin. The volume of the gels was progressively reduced as the concentration of glutaraldehyde was increased or the amount of fibrinogen was decreased, but the extent of the reduction did not correlate with the changes in the diffusion coefficient.

Journal of Pharmacy and Pharmacology

® Different dissolution media were tested using Voltaren SR as a model dosage form to develop an ... more ® Different dissolution media were tested using Voltaren SR as a model dosage form to develop an in vitro / in vivo correlation for diclofenac sodium. An empirical correlation between the cumulated amount of in vitro dissolution (%) and cumulated AUC (%) was constructed by selecting an appropriate time scale. Dissolution in a water medium for 1 h, followed with simulated intestinal fluid seemed to give better correlation with the AUC in vivo. This approach was tested with four matrix tablets based on hydroxypropylmethylcellulose (HPMC) of varying grades of viscosity and at different ratios. The closeness between in vitro dissolution profile and cumulated AUC change was conclusively demonstrated for these four ® matrix tablets. Based on this result, a product named Clofen SR was then designed and was tested in vivo to compare its ® relative bioavailability with that of Voltaren SR . The results demonstrated a similar extent of absorption in terms of AUC ® ® ®

Journal of Food and Drug Analysis

A timely controlled release dosage form with minimization of transit time and pH effects of gastr... more A timely controlled release dosage form with minimization of transit time and pH effects of gastrointestinal tract for chronotherapy of propranolol was developed. Ethylcellulose (EC) and Eudragit RS selected as the controlling membrane for drug-layering non-pareil seeds (NP) or extrusion-spheronized pellets incorporated with matrix materials or osmogents were characterized in the simulated gastric fluid (SGF) and pH change medium. Results demonstrated that when propranolol was layered on NP, Eudragit RS plasticized with 30% triethylcitrate (TEC) coated at 15% level could adjust a lag time close to the reference but with a slower release rate after then, while EC plasticized with HPMC could not delay drug release at a lag time close to the reference. Furthermore, EC incorporated with lactose coated on the extrusion-spheronized pellets could adjust the lag time, but a release rate correspondingly decreased with increasing lag time. Nevertheless, coating Eudragit RS on matrix pellets as controlling membrane at different levels could adjust a desired lag time with a pulsatile release pattern. However, the lag time adjusted was only within a 5 h range. Finally, coating Eudragit RS at different level on matrix pellets containing various ratio of osmogent, NaCl or lactose, could effectively adjust a desired lag time as long as 15 h with a pulsatile release pattern to accomplish the timely controlled release with minimization of the pH effects of gastrointestinal tract that could meet the clinical need for chronotherapy of propranolol.

Journal of Chromatography B: Biomedical Sciences and Applications, 1999

A modified high-performance chromatographic method using UV detection was developed for determina... more A modified high-performance chromatographic method using UV detection was developed for determination of tramadol concentration in human plasma. Plasma samples were extracted with ethyl acetate in a one-step liquid–liquid extraction (recovery 88.5±2.1%). Analysis of the extract was performed on a reversed-phase LiChrospher 60 RP-select B column with a particle size of 5 μm. The mobile phase consisted of 0.05 M

PLOS ONE, 2015

A mycelial mattress of Rhizopus stolonifer obtained from a liquid static culture was utilized for... more A mycelial mattress of Rhizopus stolonifer obtained from a liquid static culture was utilized for wound dressing and biomedical use. Following screening of mutants induced by UV radiation, F6, exhibiting delayed sporangium formation was selected because its sporangium maturation exhibited a 5-day delay without significant loss of mycelial weight compared to the wild type. The sporangium-free mycelial mattress from the sporangiospore culture of F6 was treated with 1N sodium hydroxide NaOH at 85°C for 2 h to produce a sponge-like membrane named Rhizochitin. The trifluoroacetic acid hydrolysate of Rhizochitin contained 36% N-acetylglucosamine and 53% hexose respectively detected by the Elson-Morgen and phenol-sulfuric acid methods. Results indicated the wound area in rats covered with Rhizochitin was 40% less than that of the uncovered group. Rhizochitin decreased the expression of PDGF in the proliferation stage, increased the expression of TGF-β in the inflammation and proliferation stages, and increased the expression of VEGF in the inflammation and proliferation stages. Rhizochitin inhibited secretion of matrix metalloproteinase-9 on days 1, 7, 9, and 12 and matrix metalloproteinase-2 on days 3, 7, 9, and 12. It was concluded that Rhizochitin has beneficial properties of biocompatible, biodegradable, and wound healing.

International Journal of Pharmaceutics, 1994

International Journal of Pharmaceutics, 1992

Several parameters were studied for their effect on the dissolution of diclofenac sodium from Vol... more Several parameters were studied for their effect on the dissolution of diclofenac sodium from Voltaren SR and hydroxypropylmethylcellulose (HPMC) based matrix tablets. The results indicate that addition of sodium or potassium chloride to the dissolution medium decreases the ...

International journal of pharmaceutics, Jan 13, 2005

A non-disintegrating polymeric capsule system, in which asymmetric membrane offers an improved os... more A non-disintegrating polymeric capsule system, in which asymmetric membrane offers an improved osmotic effect, was used to deliver poorly water-soluble drugs in a control manner. The capsule wall membrane was made by a phase inversion process, in which asymmetric membrane was formed on stainless-steel mold pins by dipping the mold pins into a coating solution containing a polymeric material followed by dipping into a quench solution. This study evaluates the influence of coating formulation that was cellulose acetate (CA), ethylcellulose (EC), and plasticizer (glycerin and triethyl citrate). Results show capsule that made by CA with glycerin (formulation A), which appear in asymmetric structure and are able to release chlorpheniramine maleate (CM) in significant percentage. Two poorly water-soluble drugs of felodipine (FL) and nifedipine (NF) were selected as the model drug to demonstrate how the controlled release characteristics can be manipulated by the design of polymeric capsul...

International journal of pharmaceutics, Jan 8, 2005

In this study, topical minoxidil solutions supplemented with TPGS in cosolvent systems of various... more In this study, topical minoxidil solutions supplemented with TPGS in cosolvent systems of various compositions consisting of water, alcohol, and polyethylene glycol 400 were designed to evaluate the efficacy of promoting hair growth after topical application and the safety in terms of the amount of minoxidil absorbed through the skin into the circulation using C57BL/6J mice as a model. The commercial product of 2% Regaine) was used as the positive control. The role, which sulfotransferase activity plays in hair growth with treatment using minoxidil, was determined as well. The results revealed that the addition of 0.5% TPGS was able to enhance the proliferation of hair, but an increase in the amount of TPGS to 2% led to deterioration in the enhancement of hair growth. At the higher added amount (2.0%) of TPGS, the promotion of hair growth was slightly reduced for both cosolvent formulations F1 (100% water) and F3 (100% PEG 400), whereas it was reduced to a greater extent for the cos...

International journal of pharmaceutics, Jan 17, 2006

In this study, chitosan capsules with asymmetric membrane to induce osmotic effects and in situ f... more In this study, chitosan capsules with asymmetric membrane to induce osmotic effects and in situ formation of the delivery orifice were optimally prepared and characterized. Chitosan capsules were formed on stainless steel mold pins by dipping the pins into a chitosan solution followed by forming asymmetric structure by dipping into a quenching solution containing tripolyphosphate (TPP) to cause an ionic cross-linking reaction between the outer layer of chitosan and TPP. Factors influencing the properties of the capsule membrane, such as the molecular weight of chitosan, the dipping solution and dipping time, and the quenching solution and time, were optimized to successfully produce osmotic chitosan capsules with asymmetric membrane using chitosans that possessed different viscosities. In situ formation of a delivery orifice on the asymmetric membrane of the chitosan capsule was proven by the observation of a jet stream of chlorophyll being released from the capsule. Drugs with diff...

International journal of nanomedicine, 2012

To resolve problems of long treatment durations and frequent administration of the antifungal age... more To resolve problems of long treatment durations and frequent administration of the antifungal agent terbinafine (TB), solid lipid nanoparticles (SLNs) with the ability to load lipophilic drugs and nanosize were developed. The SLNs were manufactured by a microemulsion technique in which glyceryl monostearate (GMS), glyceryl behenate (Compritol(®) 888; Gattefossé), and glyceryl palmitostearate (Precirol(®) ATO 5; Gattefossé) were used as the solid lipid phases, Tween(®) and Cremophor(®) series as the surfactants, and propylene glycol as the cosurfactant to construct ternary phase diagrams. The skin of nude mice was used as a barrier membrane, and penetration levels of TB of the designed formulations and a commercial product, Lamisil(®) Once™ (Novartis Pharmaceuticals), in the stratum corneum (SC), viable epidermis, and dermis were measured; particle sizes were determined as an indicator of stability. The optimal SLN system contained a <5% lipid phase and >50% water phase. The ad...

International journal of nanomedicine, 2012

The extraction residue of the Ganoderma fruiting body, named sacchachitin, has been demonstrated ... more The extraction residue of the Ganoderma fruiting body, named sacchachitin, has been demonstrated to have the potential to enhance cutaneous wound healing by inducing cell proliferation. In this study, a nanogel formed from micronized sacchachitin (mSC) was investigated for the potential treatment of superficial chemical corneal burns. Reportedly, mSC has been produced successfully and its chemical properties confirmed, and physical and rheological properties characterized. An in vitro cell proliferation study has revealed that at the concentrations of 200, 300, and 400 microg/mL, mSC nanogel significantly increased Statens Seruminstitut rabbit corneal (SIRC) cell proliferation after 24 hours of incubation. In cell migration assay, migration of SIRC cell to wound closure was observed after 24 hours of incubation with the addition of 200 microg/mL mSC of nanogel. In an animal study, acceleration of corneal wound healing was probably due to the inhibition of proteolysis. In conclusion,...

International Journal of Nanomedicine, 2016

Quercetin (Que) is known to have biological benefits including an anticancer effect, but low wate... more Quercetin (Que) is known to have biological benefits including an anticancer effect, but low water solubility limits its clinical application. The aim of this study was to develop a lecithin-based mixed polymeric micelle (LMPM) delivery system to improve the solubility and bioavailability of Que. The optimal Que-LMPM, composed of Que, lecithin, Pluronic(®) P123, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy[poly(ethylene glycol)-2000] in a proportion of 3:1:17.5:2.5 (w/w), was prepared by a thin-film method. The average size, polydispersion index, encapsulating efficiency, and drug loading of Que-LMPM were 61.60±5.02 nm, 0.589±0.198, 96.87%±9.04%, and 12.18%±1.11%, respectively. The solubility of Que in the Que-LMPM system increased to 5.81 mg/mL, compared to that of free Que in water of 0.17-7.7 μg/mL. The Que-LMPM system presented a sustained-release property in vitro. The in vitro cytotoxicity assay showed that the 50% inhibitory concentration values toward MCF-7 breast cancer cells for free Que, blank LMPMs, and Que-LMPMs were &gt;200, &gt;200, and 110 μM, respectively, indicating the nontoxicity of the LMPM carrier, but the LMPM formulation enhanced the cytotoxicity of Que against MCF-7 cells. A cellular uptake assay also confirmed the intake of Que-LMPM by MCF-7 cells. An in vivo pharmacokinetic study demonstrated that Que-LMPMs had higher area under the concentration-time curve and a longer half-life, leading to better bioavailability compared to a free Que injection. Due to their nanosize, core-shell structure, and solubilization potential, LMPMs were successfully developed as a drug delivery system for Que to improve its solubility and bioavailability.

Journal of pharmaceutical sciences, Jan 14, 2016

The aim of the present study was to prepare sublingual delivery systems for sildenafil and evalua... more The aim of the present study was to prepare sublingual delivery systems for sildenafil and evaluate its relative bioavailability after sublingual administration in rabbits to attain a rapid onset of action with good efficacy at lower doses. For sublingual application, sildenafil and its citrate were formulated in 2 different dosage forms: the first was a sublingual spray consisting of sildenafil in 2 microemulsion systems, oleic acid or propylene glycol (PG), and the second was sublingual tablets prepared with various granulated sublingual sprays adsorbed onto a silicate adsorbant (Florite(®) R), binders (Cyclocel(®) or EMDEX(®)), and disintegrants (Ac-Di-Sol(®) or Kollidon(®) CL). Results showed that sublingual absorption of sildenafil spray prepared with PG was fairly rapid. At a 0.5-mg dose, the mean onset of action was 1.3 ± 0.6 min and lasted for about 1.5 h according to the pharmacokinetic studies. In vivo studies also showed that for sublingual tablets formulated with sildena...

Colloids and surfaces. B, Biointerfaces, Jan 18, 2016

Doxorubicin (DOX) thermosensitive hydrogels (TSHs) incorporated with docetaxel (DOC)-loaded mixed... more Doxorubicin (DOX) thermosensitive hydrogels (TSHs) incorporated with docetaxel (DOC)-loaded mixed micelles were developed to co-deliver these two drugs through a TSH system, DH700kMF-13.5/M-DocLF, to improve local cancer therapy and reduce side effects. First, Pluronics-based DOC-loaded mixed micelles were developed and optimized. The optimal formulation designated as M-DocLF was composed of 1mg/g docetaxel, 15mg/g Pluronic F127 (PF127), and 45mg/g Pluronic L121 (PL121). Rheological tests showed that DH700kMF-13.5/M-DocLF was an injectable flowing solution, which formed a nonflowing gel at body temperature. After intratumoral (IT) or peritumoral (PT) administration, DH700kMF-13.5/M-DocLF demonstrated efficient growth inhibition of CT-26 tumors in a Balb/c mice model. The tumor inhibitory rate after IT administration of DH700kMF-13.5/M-DocLF was 92.4%, followed by 85.8%, 75.6%, 62.9%, 50.6%, and 49.5% for DH700kMF-15, free DOX, F-13.5/M-DocLF, Tynen (DOC solution), and M-DocLF, respe...

PloS one, 2016

There has been considerable interest in the biological functions of astaxanthin and its potential... more There has been considerable interest in the biological functions of astaxanthin and its potential applications in the nutraceutical, cosmetics, food, and feed industries in recent years. However, the unstable structure of astaxanthin considerably limits its application. Therefore, this study reports the encapsulation of astaxanthin in calcium alginate beads using the extrusion method to improve its stability. This study also evaluates the stability of the encapsulated astaxanthin under different storage conditions. The evaluation of astaxanthin stability under various environmental factors reveals that temperature is the most influential environmental factor in astaxanthin degradation. Stability analysis shows that, regardless of the formulation used, the content of astaxanthin encapsulated in alginate beads remains above 90% of the original amount after 21 days of storage at 25°C. These results suggest that the proposed technique is a promising way to enhance the stability of other...

International journal of nanomedicine, 2015

To alleviate the inherent problems of amphotericin B (AmB), such as poor water solubility and nep... more To alleviate the inherent problems of amphotericin B (AmB), such as poor water solubility and nephrotoxicity, a novel self-assembling mixed polymeric micelle delivery system based on lecithin and combined with amphiphilic polymers, Pluronic(®), Kolliphor(®), d-alpha tocopheryl polyethylene glycol succinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(poly(ethylene glycol)-2000 (DSPE-PEG2K) was developed. An optimal formulation (Ambicelles) composed of AmB:lecithin:DSPE-PEG2K in a 1:1:10 weight ratio was obtained. The particle size, polydispersion index, drug encapsulation efficiency, and drug loading were 187.20±10.55 nm, 0.51±0.017, 90.14%, and 7.51%, respectively, and the solubility was increased from 0.001 to 5 mg/mL. Compared with that of Fungizone(®), the bioavailability of Ambicelles administered intravenously and orally increased 2.18- and 1.50-fold, respectively. Regarding the in vitro cytotoxicity, Ambicelles had a higher cell viability than free AmB solut...

Purpose: To obtain a synergy between the swelling indexes of swellable polymers with a combinatio... more Purpose: To obtain a synergy between the swelling indexes of swellable polymers with a combination of several swelling functionalities in the unit, the investigation of different types of swellable polymers and addition of an ionic complex of polyelectrolytes with regard to the swelling behavior was conducted in this study. Methods: Physical characterizations of the tablets, including a swelling index based on weight variation and visual swelling observations, were carried out. Results: Of the four different grades of HEC 250 examined (H, HX, HHX and M), HEC 250HHX exhibited the greatest swelling index. Lower molecular weight PEO, varying from Mw 00K to Mw 900K, exhibited a low swelling index and dissolved almost completely after immersion for 2 to 4 h in the medium. However, the swelling ability of PEO (Mw 8,000K) was found to be sustainable to an extent greater than that for HEC 250HHX. Combination of a lower molecular weight PEO (Mw 900K) with HEC 250HHX resulted in a lower swelling index than that for HEC 250HHX alone, whereas a high molecular weight PEO (Mw 8,000K) incorporated with HEC 250HHX resulted in a higher swelling rate. However, the addition of an ionic complex of polyelectrolytes produced only a slight improvement in swelling index. Conclusion: HEC exhibited a suitable swelling index apart from the higher molecular weight PEO (Mw 8,000K). The addition of 50% Carbopol in HEC would be preferable to increase the swelling of the tablet. The swelling index obtained from the formulation with 0% to 50% of chitosan showed a good swelling index in the pH .2 media, but the degree of swelling size was not high enough as required.

Journal of parenteral science and technology: a publication of the Parenteral Drug Association

In this study, fibrin beads containing macromolecules of different molecular weight were prepared... more In this study, fibrin beads containing macromolecules of different molecular weight were prepared in two different size distributions by varying the ratio of oleic acid to mineral oil in the oil phase of the emulsion system. The release characteristics were examined and compared. A dependence on the size of the fibrin microspheres for macromolecule release from fibrin microspheres was demonstrated: the smaller the size of the fibrin microspheres, the faster the release rate of the macromolecules. In addition, the apparent diffusion coefficient was found to be a function of the molecular size of the macromolecules. As a result, the larger the molecular weight of the macromolecules, the smaller the apparent diffusion coefficient. However, the release of lysozyme and insulin dissolved in 0.1 N HCI solution was undetectable.

Drug design and delivery

Glutaraldehyde treatment of dexamethasone-containing cylindrical fibrin gels (obtained by the thr... more Glutaraldehyde treatment of dexamethasone-containing cylindrical fibrin gels (obtained by the thrombin-induced polymerization of fibrinogen in the presence of the drug) causes cross-linking of the gels and modification of the pore structure. The effect on the release of dexamethasone was assessed by measuring the diffusion coefficient of the drug across treated and untreated gels; diffusion across the treated gels was significantly decreased as compared with untreated gels, but was little affected by the concentration of glutaraldehyde used in the treatment. In biodegradable tests, the treated gels (all concentrations of glutaraldehyde) were resistant to digestion even in the presence of plasmin, but untreated gels were digested, and the digestion rate was accelerated by plasmin. The volume of the gels was progressively reduced as the concentration of glutaraldehyde was increased or the amount of fibrinogen was decreased, but the extent of the reduction did not correlate with the changes in the diffusion coefficient.

Journal of Pharmacy and Pharmacology

® Different dissolution media were tested using Voltaren SR as a model dosage form to develop an ... more ® Different dissolution media were tested using Voltaren SR as a model dosage form to develop an in vitro / in vivo correlation for diclofenac sodium. An empirical correlation between the cumulated amount of in vitro dissolution (%) and cumulated AUC (%) was constructed by selecting an appropriate time scale. Dissolution in a water medium for 1 h, followed with simulated intestinal fluid seemed to give better correlation with the AUC in vivo. This approach was tested with four matrix tablets based on hydroxypropylmethylcellulose (HPMC) of varying grades of viscosity and at different ratios. The closeness between in vitro dissolution profile and cumulated AUC change was conclusively demonstrated for these four ® matrix tablets. Based on this result, a product named Clofen SR was then designed and was tested in vivo to compare its ® relative bioavailability with that of Voltaren SR . The results demonstrated a similar extent of absorption in terms of AUC ® ® ®

Journal of Food and Drug Analysis

A timely controlled release dosage form with minimization of transit time and pH effects of gastr... more A timely controlled release dosage form with minimization of transit time and pH effects of gastrointestinal tract for chronotherapy of propranolol was developed. Ethylcellulose (EC) and Eudragit RS selected as the controlling membrane for drug-layering non-pareil seeds (NP) or extrusion-spheronized pellets incorporated with matrix materials or osmogents were characterized in the simulated gastric fluid (SGF) and pH change medium. Results demonstrated that when propranolol was layered on NP, Eudragit RS plasticized with 30% triethylcitrate (TEC) coated at 15% level could adjust a lag time close to the reference but with a slower release rate after then, while EC plasticized with HPMC could not delay drug release at a lag time close to the reference. Furthermore, EC incorporated with lactose coated on the extrusion-spheronized pellets could adjust the lag time, but a release rate correspondingly decreased with increasing lag time. Nevertheless, coating Eudragit RS on matrix pellets as controlling membrane at different levels could adjust a desired lag time with a pulsatile release pattern. However, the lag time adjusted was only within a 5 h range. Finally, coating Eudragit RS at different level on matrix pellets containing various ratio of osmogent, NaCl or lactose, could effectively adjust a desired lag time as long as 15 h with a pulsatile release pattern to accomplish the timely controlled release with minimization of the pH effects of gastrointestinal tract that could meet the clinical need for chronotherapy of propranolol.

Journal of Chromatography B: Biomedical Sciences and Applications, 1999

A modified high-performance chromatographic method using UV detection was developed for determina... more A modified high-performance chromatographic method using UV detection was developed for determination of tramadol concentration in human plasma. Plasma samples were extracted with ethyl acetate in a one-step liquid–liquid extraction (recovery 88.5±2.1%). Analysis of the extract was performed on a reversed-phase LiChrospher 60 RP-select B column with a particle size of 5 μm. The mobile phase consisted of 0.05 M

PLOS ONE, 2015

A mycelial mattress of Rhizopus stolonifer obtained from a liquid static culture was utilized for... more A mycelial mattress of Rhizopus stolonifer obtained from a liquid static culture was utilized for wound dressing and biomedical use. Following screening of mutants induced by UV radiation, F6, exhibiting delayed sporangium formation was selected because its sporangium maturation exhibited a 5-day delay without significant loss of mycelial weight compared to the wild type. The sporangium-free mycelial mattress from the sporangiospore culture of F6 was treated with 1N sodium hydroxide NaOH at 85°C for 2 h to produce a sponge-like membrane named Rhizochitin. The trifluoroacetic acid hydrolysate of Rhizochitin contained 36% N-acetylglucosamine and 53% hexose respectively detected by the Elson-Morgen and phenol-sulfuric acid methods. Results indicated the wound area in rats covered with Rhizochitin was 40% less than that of the uncovered group. Rhizochitin decreased the expression of PDGF in the proliferation stage, increased the expression of TGF-β in the inflammation and proliferation stages, and increased the expression of VEGF in the inflammation and proliferation stages. Rhizochitin inhibited secretion of matrix metalloproteinase-9 on days 1, 7, 9, and 12 and matrix metalloproteinase-2 on days 3, 7, 9, and 12. It was concluded that Rhizochitin has beneficial properties of biocompatible, biodegradable, and wound healing.

International Journal of Pharmaceutics, 1994

International Journal of Pharmaceutics, 1992

Several parameters were studied for their effect on the dissolution of diclofenac sodium from Vol... more Several parameters were studied for their effect on the dissolution of diclofenac sodium from Voltaren SR and hydroxypropylmethylcellulose (HPMC) based matrix tablets. The results indicate that addition of sodium or potassium chloride to the dissolution medium decreases the ...

International journal of pharmaceutics, Jan 13, 2005

A non-disintegrating polymeric capsule system, in which asymmetric membrane offers an improved os... more A non-disintegrating polymeric capsule system, in which asymmetric membrane offers an improved osmotic effect, was used to deliver poorly water-soluble drugs in a control manner. The capsule wall membrane was made by a phase inversion process, in which asymmetric membrane was formed on stainless-steel mold pins by dipping the mold pins into a coating solution containing a polymeric material followed by dipping into a quench solution. This study evaluates the influence of coating formulation that was cellulose acetate (CA), ethylcellulose (EC), and plasticizer (glycerin and triethyl citrate). Results show capsule that made by CA with glycerin (formulation A), which appear in asymmetric structure and are able to release chlorpheniramine maleate (CM) in significant percentage. Two poorly water-soluble drugs of felodipine (FL) and nifedipine (NF) were selected as the model drug to demonstrate how the controlled release characteristics can be manipulated by the design of polymeric capsul...

International journal of pharmaceutics, Jan 8, 2005

In this study, topical minoxidil solutions supplemented with TPGS in cosolvent systems of various... more In this study, topical minoxidil solutions supplemented with TPGS in cosolvent systems of various compositions consisting of water, alcohol, and polyethylene glycol 400 were designed to evaluate the efficacy of promoting hair growth after topical application and the safety in terms of the amount of minoxidil absorbed through the skin into the circulation using C57BL/6J mice as a model. The commercial product of 2% Regaine) was used as the positive control. The role, which sulfotransferase activity plays in hair growth with treatment using minoxidil, was determined as well. The results revealed that the addition of 0.5% TPGS was able to enhance the proliferation of hair, but an increase in the amount of TPGS to 2% led to deterioration in the enhancement of hair growth. At the higher added amount (2.0%) of TPGS, the promotion of hair growth was slightly reduced for both cosolvent formulations F1 (100% water) and F3 (100% PEG 400), whereas it was reduced to a greater extent for the cos...

International journal of pharmaceutics, Jan 17, 2006

In this study, chitosan capsules with asymmetric membrane to induce osmotic effects and in situ f... more In this study, chitosan capsules with asymmetric membrane to induce osmotic effects and in situ formation of the delivery orifice were optimally prepared and characterized. Chitosan capsules were formed on stainless steel mold pins by dipping the pins into a chitosan solution followed by forming asymmetric structure by dipping into a quenching solution containing tripolyphosphate (TPP) to cause an ionic cross-linking reaction between the outer layer of chitosan and TPP. Factors influencing the properties of the capsule membrane, such as the molecular weight of chitosan, the dipping solution and dipping time, and the quenching solution and time, were optimized to successfully produce osmotic chitosan capsules with asymmetric membrane using chitosans that possessed different viscosities. In situ formation of a delivery orifice on the asymmetric membrane of the chitosan capsule was proven by the observation of a jet stream of chlorophyll being released from the capsule. Drugs with diff...

International journal of nanomedicine, 2012

To resolve problems of long treatment durations and frequent administration of the antifungal age... more To resolve problems of long treatment durations and frequent administration of the antifungal agent terbinafine (TB), solid lipid nanoparticles (SLNs) with the ability to load lipophilic drugs and nanosize were developed. The SLNs were manufactured by a microemulsion technique in which glyceryl monostearate (GMS), glyceryl behenate (Compritol(®) 888; Gattefossé), and glyceryl palmitostearate (Precirol(®) ATO 5; Gattefossé) were used as the solid lipid phases, Tween(®) and Cremophor(®) series as the surfactants, and propylene glycol as the cosurfactant to construct ternary phase diagrams. The skin of nude mice was used as a barrier membrane, and penetration levels of TB of the designed formulations and a commercial product, Lamisil(®) Once™ (Novartis Pharmaceuticals), in the stratum corneum (SC), viable epidermis, and dermis were measured; particle sizes were determined as an indicator of stability. The optimal SLN system contained a <5% lipid phase and >50% water phase. The ad...

International journal of nanomedicine, 2012

The extraction residue of the Ganoderma fruiting body, named sacchachitin, has been demonstrated ... more The extraction residue of the Ganoderma fruiting body, named sacchachitin, has been demonstrated to have the potential to enhance cutaneous wound healing by inducing cell proliferation. In this study, a nanogel formed from micronized sacchachitin (mSC) was investigated for the potential treatment of superficial chemical corneal burns. Reportedly, mSC has been produced successfully and its chemical properties confirmed, and physical and rheological properties characterized. An in vitro cell proliferation study has revealed that at the concentrations of 200, 300, and 400 microg/mL, mSC nanogel significantly increased Statens Seruminstitut rabbit corneal (SIRC) cell proliferation after 24 hours of incubation. In cell migration assay, migration of SIRC cell to wound closure was observed after 24 hours of incubation with the addition of 200 microg/mL mSC of nanogel. In an animal study, acceleration of corneal wound healing was probably due to the inhibition of proteolysis. In conclusion,...