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Sei Kwang Hahn - One of the best experts on this subject based on the ideXlab platform.
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Selectively crosslinked hyaluronic acid hydrogels for sustained Release Formulation of erythropoietin
Journal of biomedical materials research. Part A, 2006Co-Authors: Keiko Motokawa, Sei Kwang Hahn, Teruo Nakamura, Hajime Miyamoto, Tsuyoshi ShimobojiAbstract:A novel sustained Release Formulation of erythropoietin (EPO) was developed using hyaluronic acid (HA) hydrogels. For the preparation of HA hydrogels, adipic acid dihydrazide grafted HA (HA-ADH) was synthesized and analyzed with (1)H NMR. The degree of HA-ADH modification was about 69%. EPO was in situ encapsulated into HA-ADH hydrogels through a selective cross-linking reaction of bis(sulfosuccinimidyl) suberate (BS(3)) to hydrazide group (pK(a) = 3.0) of HA-ADH rather than to amine group (pK(a) > 9) of EPO. The denaturation of EPO during HA-ADH hydrogel synthesis was drastically reduced with decreasing pH from 7.4 to 4.8. The specific reactivity of BS(3) to hydrazide at pH = 4.8 might be due to its low pK(a) compared with that of amine. In vitro Release of EPO in phosphate buffered saline at 37 degrees C showed that EPO was Released rapidly for 2 days and then slowly up to 4 days from HA-ADH hydrogels. When the hydrogels were dried at 37 degrees C for a day, however, longer Release of EPO up to 3 weeks could be demonstrated. According to in vivo Release test of EPO from HA-ADH hydrogels in SD rats, elevated EPO concentration higher than 0.1 ng/mL could be maintained from 7 days up to 18 days depending on the preparation methods of HA-ADH hydrogels. There was no adverse effect during and after HA-ADH hydrogel implantation.
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Sustained Release Formulation of erythropoietin using hyaluronic acid hydrogels crosslinked by Michael addition.
International journal of pharmaceutics, 2006Co-Authors: Sei Kwang Hahn, Hajime Miyamoto, Tsuyoshi ShimoboujiAbstract:A novel sustained Release Formulation of erythropoietin (EPO) was successfully developed using hyaluronic acid (HA) hydrogels crosslinked by Michael addition. Adipic acid dihydrazide grafted HA (HA-ADH) was prepared and then modified into methacrylated HA (HA-MA). (1)H NMR analysis showed that the degrees of HA-ADH and HA-MA modification were 69 and 29 mol%, respectively. Using the specific crosslinkers of dithiothreitol (DTT) and peptide linker, EPO was loaded during HA-MA hydrogel preparation by Michael addition chemistry between thiol and methacrylate groups. The amount of EPO recovered from both hydrogels after degradation with hyaluronidase SD (HAse SD) was about 90%. The crosslinking reaction with peptide linker (GCYKNRDCG) was faster than that with DTT. The gelation time was about 30 min for peptide linker and 180 min for DTT. In vitro Release test of EPO from HA-MA hydrogel at 37 degrees C showed that EPO was Released rapidly for 2 days and then slowly up to 7 days from HA-MA hydrogels. The Released EPO appeared to be intact from the analysis with RP-HPLC. According to in vivo Release test of EPO from HA-MA hydrogels crosslinked with the peptide linker in Sprague-Dawley (SD) rats, elevated plasma concentration of EPO was maintained up to 7 days. There was no adverse effect during and after the in vivo tests.
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Sustained Release Formulation of erythropoietin using hyaluronic acid hydrogels crosslinked by Michael addition.
International Journal of Pharmaceutics, 2006Co-Authors: Sei Kwang Hahn, Hajime Miyamoto, Tsuyoshi ShimoboujiAbstract:Abstract A novel sustained Release Formulation of erythropoietin (EPO) was successfully developed using hyaluronic acid (HA) hydrogels crosslinked by Michael addition. Adipic acid dihydrazide grafted HA (HA-ADH) was prepared and then modified into methacrylated HA (HA-MA). 1H NMR analysis showed that the degrees of HA-ADH and HA-MA modification were 69 and 29 mol%, respectively. Using the specific crosslinkers of dithiothreitol (DTT) and peptide linker, EPO was loaded during HA-MA hydrogel preparation by Michael addition chemistry between thiol and methacrylate groups. The amount of EPO recovered from both hydrogels after degradation with hyaluronidase SD (HAse SD) was about 90%. The crosslinking reaction with peptide linker (GCYKNRDCG) was faster than that with DTT. The gelation time was about 30 min for peptide linker and 180 min for DTT. In vitro Release test of EPO from HA-MA hydrogel at 37 °C showed that EPO was Released rapidly for 2 days and then slowly up to 7 days from HA-MA hydrogels. The Released EPO appeared to be intact from the analysis with RP-HPLC. According to in vivo Release test of EPO from HA-MA hydrogels crosslinked with the peptide linker in Sprague–Dawley (SD) rats, elevated plasma concentration of EPO was maintained up to 7 days. There was no adverse effect during and after the in vivo tests.
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Characterization and In Vivo Study of Sustained-Release Formulation of Human Growth Hormone Using Sodium Hyaluronate
Pharmaceutical Research, 2004Co-Authors: Sei Kwang HahnAbstract:Purpose. Aiming at once-a-week injection, a novel sustained Release Formulation of recombinant human growth hormone (SR-hGH) using sodium hyaluronate was developed for the treatment of children who have growth failure due to the lack of adequate secretion of endogenous growth hormone. Methods. SR-hGH was produced in the form of solid microparticle using a Niro spray dryer and characterized by Malvern particle size analysis, scanning electron microscopy (SEM), size exclusion chromatography (SEC), reverse phase-high-performance chromatography (RP-HPLC), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). After in vitro Release test, pharmacokinetic and pharmacodynamic studies were carried out in beagle dogs. SR-hGH was dispersed in medium-chain triglyceride (MCT) and administered at a dose of 1.0 mg hGH/kg subcutaneously. Results. SR-hGH microparticles were successfully produced with a mean particle size of 5.6 ± 1.0 μm. Physicochemical analysis with SEC, RP-HPLC, and SDS-PAGE showed that hGH extracted from SR-hGH was intact and comparable to that of hGH bulk standard indicating no structural change in hGH during the Formulation processes. Monomeric content of hGH recovered from SR-hGH was 97.4% by SEC analysis, and its purity was 96% by RP-HPLC analysis. In vitro Release test showed the sustained-Release characteristics of SR-hGH up to 48 h with the complete Release of hGH loaded. The continuous and monotonous Release profile observed in in vitro Release test was supported by pharmacokinetic study in beagle dogs. Delayed absorption of hGH was observed with C_max of 69.5 ± 8.0 ng/ml and T_max between 10 and 12 h. The administration of SR-hGH induced elevation of serum insulin-like growth factor-I (IGF-I) level for 6 days with a maximum value higher than the predose level by ca. 350 ng/ml. After 6 days, IGF-I level returned to the initial baseline level. Conclusions. Sustained-Release Formulation of hGH for once-a-week injection was successfully developed using high-molecular-weight sodium hyaluronate. No adverse effect was observed during and after the in vivo test using beagle dogs.
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Characterization and in vivo study of sustained-Release Formulation of human growth hormone using sodium hyaluronate.
Pharmaceutical research, 2004Co-Authors: Sei Kwang Hahn, Sun Jin Kim, Myung Jin Kim, Duk Hee KimAbstract:Purpose. Aiming at once-a-week injection, a novel sustained Release Formulation of recombinant human growth hormone (SR-hGH) using sodium hyaluronate was developed for the treatment of children who have growth failure due to the lack of adequate secretion of endogenous growth hormone.
W. M. Zeng - One of the best experts on this subject based on the ideXlab platform.
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Oral controlled Release Formulation for highly water-soluble drugs: drug--sodium alginate--xanthan gum--zinc acetate matrix.
Drug Development and Industrial Pharmacy, 2004Co-Authors: W. M. ZengAbstract:An oral controlled Release Formulation matrix for highly water‐soluble drugs was designed and developed to achieve a 24‐hour Release profile. Using ranitidine HCl as a model drug, sodium alginate Formulation matrices containing xanthan gum or zinc acetate or both were investigated. The caplets for these Formulations were prepared by direct compression and the in vitro Release tests were carried out in simulated intestinal fluid (SIF, pH7.5) and simulated gastric fluid (SGF, pH1.2). The Release of the drug in the sodium alginate Formulation containing only xanthan gum completed within 12 hours in the SIF, while the drug Release in the sodium alginate Formulation containing only zinc acetate finished almost within 2 hours in the same medium. Only the sodium alginate Formulation containing both xanthan gum and zinc acetate achieved a 24‐hour Release profile, either in the SIF or in the pH change medium. In the latter case, the caplet Released in the SGF for 2 hours was immediately transferred into the SIF to...
Duk Hee Kim - One of the best experts on this subject based on the ideXlab platform.
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Characterization and in vivo study of sustained-Release Formulation of human growth hormone using sodium hyaluronate.
Pharmaceutical research, 2004Co-Authors: Sei Kwang Hahn, Sun Jin Kim, Myung Jin Kim, Duk Hee KimAbstract:Purpose. Aiming at once-a-week injection, a novel sustained Release Formulation of recombinant human growth hormone (SR-hGH) using sodium hyaluronate was developed for the treatment of children who have growth failure due to the lack of adequate secretion of endogenous growth hormone.
Greg L Plosker - One of the best experts on this subject based on the ideXlab platform.
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glipizide a review of the pharmacoeconomic implications of the extended Release Formulation in type 2 diabetes mellitus
PharmacoEconomics, 2000Co-Authors: Rachel H Foster, Greg L PloskerAbstract:Glipizide is a second generation sulphonylurea agent that is available in a Gastrointestinal Therapeutic System (GITS) extended-Release Formulation. Glipizide GITS provides more stable plasma drug concentrations than the immediate-Release Formulation and the once-daily regimen may optimise patient compliance. In patients with type 2 diabetes mellitus, glipizide GITS is at least as effective as the immediate-Release Formulation of glipizide in providing glycaemic control, and may have a greater effect on fasting plasma glucose levels. Any therapeutic advantage over other antidiabetic agents remains to be established, but in a preliminary report (n = 40) glipizide GITS provided better glycaemic control and produced less fasting insulinaemia than glibenclamide (glyburide). The incidence of hypoglycaemic symptoms with glipizide GITS is low (
J. Moncrieff - One of the best experts on this subject based on the ideXlab platform.
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The effects of omeprazole-induced hypochlorhydria on absorption of theophylline from a sustained-Release Formulation
European Journal of Clinical Pharmacology, 1992Co-Authors: K. Sommers, J. R. Snyman, J. MoncrieffAbstract:The present study was designed to investigate the effects of raised intragastric pH on the absorption of theophylline from a sustained-Release Formulation. Six healthy male volunteers participated in the cross-over randomised study and on one of two occasions were pretreated with 240 mg omeprazole, administered in three divided doses over the 22 h preceding the test. The sulphasalazine/sulphapyridine method of assessing oral-caecal transit time was implemented in order to assess upper bowel and colonic absorption. The mean fraction absorbed — time profile was calculated from serial serum theophylline concentration measurements by a modification of the Wagner-Nelson equation. During hypochlorhydria the mean oral-caecal transit time was 4.6 h, mean time to 90% absorption 6.8 h, and the percentage theophylline presumably to be absorbed from the colon 32.3. The corresponding values with normochlorhydria were, respectively, 3.8 h, 8.5 h, and 57.5%. The shorter oral-caecal transit time and lesser upper bowel absorption during normochlorhydria is postulated to result from motilin Release due to duodenal acidification. Gastric hypoacidity resulted in significantly increased cumulative fractions of theophylline absorbed during a 3.5 h period, starting 0.5 h after breakfast. Possibly hypochlorhydria amplifies the increased motility which follows the intake of a meal, resulting in increased peristalsis and antiperistalsis, with more rapid drug absorption.
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The influence of codeine, propantheline and metoclopramide on small bowel transit and theophylline absorption from a sustained-Release Formulation.
British journal of clinical pharmacology, 1992Co-Authors: D. K. Sommers, J. Moncrieff, E. C. Meyer, M. Van Wyk, Jacques Rene Snyman, R J GrimbeekAbstract:1. The effects of the anticholinergic agent, propantheline, the opiate, codeine, and the prokinetic agent, metoclopramide, on oral-caecal transit time and on the absorption of theophylline from a sustained-Release Formulation were examined in six healthy male volunteers. 2. A cross-over randomised sequence design was followed, allowing at least 2 weeks interval between studies. On each occasion 500 mg theophylline in a sustained-Release Formulation was taken simultaneously with 2 g sulphasalazine at zero time. On three of the four occasions one of the following treatments was given concurrently at -0.5 h, +3.5 h, and +7.5 h: 30 mg codeine phosphate, 30 mg propantheline bromide, or 10 mg metoclopramide monohydrochloride. 3. The appearance of sulphapyridine in the plasma was used to assess oral-caecal transit time and the mean fraction absorbed-time profile of theophylline was calculated from serial serum theophylline concentration measurements using the Wagner-Nelson method. 4. Codeine increased the mean (s.d.) oral-caecal time (h) significantly (5.14 +/- 0.94) compared with the control value (3.78 +/- 0.34). Propantheline inhibited peristaltic contractions to such an extent that the oral-caecal transit time in five of the volunteers was between 9 and 25 h, while sulphapyridine appeared in the 9 h serum sample of the sixth. Metoclopramide did not significantly alter the oral-caecal transit time. 5. Despite the observed changes in oral-caecal transit time the rate and extent of theophylline absorption was similar with all regimens.
