Biomedical subjects

Seong Hoon Jeong

Publications and source records attributed to Seong Hoon Jeong.

11 recordsLinked to original sources

PubMed2007

Drug release properties of polymer coated ion-exchange resin complexes: experimental and theoretical evaluation.

Although ion-exchange resins have been used widely as drug delivery systems, their exact release kinetics has not been reported yet. Usually only the rate-limiting step has been taken into account and the rest of the steps have been ignored as instantaneous processes. To investigate the exact release kinetics of polymer-coated drug/ion-exchange resin complexes for sustained drug delivery, the results of new mathematical modeling were compared with experimental results. Drug/resin complexes with a model drug, dextromethorphan, were prepared and used as cores for fluid-bed coating. An aqueous colloidal dispersion of poly(vinyl acetate) was applied for the coating. A comprehensive mathematical model was developed using a mechanistic approach by considering diffusion, swelling, and ion-exchange processes solved by numerical techniques. The rate-limiting factor of the uncoated resin particles was diffusion through the core matrix. Similarly, in the coated particles the rate-limiting factor was diffusion through the coating membrane. The mathematical model has captured the phenomena observed during experimental evaluations and the release dynamics from uncoated and coated (at different coat levels) particles were predicted accurately (maximum RMSE 2.4%). The mathematical model is a useful tool to theoretically evaluate the drug release properties from coated ion-exchange complexes thus can be used for design purposes.

Anion Exchange Resins↗

PubMed2006

The dysbindin gene (DTNBP1) and schizophrenia: no support for an association in the Korean population.

The dysbindin gene (DTNBP1) is located in chromosome 6p22.3, one of the regions of positive linkage for schizophrenia. A strong genetic association between DTNBP1 and schizophrenia has been replicated through many recent studies. In particular, dysbindin protein has been found to play a role in the glutamate neural transmission in the brain. In this study, we attempted to replicate the previously reported positive association between DTNBP1 and schizophrenia in the Korean population. Our sample included 194 patients with schizophrenia based on DSM-IV and 351 normal controls. We genotyped five SNPs including SNP A in promoter region of DTNBP1. The allele and genotype association were analyzed and the simulated haplotype was investigated as well. As the result, we could not find a significant association of DTNBP1 with schizophrenia in this Korean sample. Additional analysis of the subgroup of schizophrenia having familial loading of major psychiatric disorders did not show association, either. In summary, DTNBP1 is not likely to be a major susceptibility gene for schizophrenia in this Korean population. This result of no association also implies possible genetic heterogeneity of schizophrenia. Further studies with more dense SNPs of the whole gene sequence for various populations will be necessary to understand the genetic contribution of DTNBP1 for the development of schizophrenia.

Adult↗

PubMed2006

Modeling film-coat non-uniformity in polymer coated pellets: a stochastic approach.

The objective of the present study is to include coating thickness non-uniformity in the development of a drug release model using coated ion-exchange pellets through the use of stochastic approaches. Drug release from ion-exchange resins was described using a Nernst-Plank model. Complexes of a model drug (dextromethorphan) and Dowex 50WX4-200 were prepared using a modified batch method and coated with Kollicoat SR 30D polymer. The deterministic model, validated using experimental drug release profiles for different coating thicknesses at 0%, 10%, 15%, 20% (w/w), was in agreement with the experimental data with a maximum root mean square error (RMSE) of 2.4%. An arbitrary Lagrangian-Eulerian approach was pursued to develop models of spherical pellets with non-uniform coating thicknesses. The Monte Carlo method was used to simulate the effect of the level of coating deformity on the cumulative drug release profile. Considering the co-existence of equal percentages of deformed and undeformed pellets in a batch, the cumulative release profile can vary by approximately +/-6% as a result of coating non-uniformity. The release profile obtained for a model of an arbitrary pellet with an actual non-uniform coating profile was in good agreement with the average release profile for the models of the theoretical randomly deformed pellets. The developed mathematical model is a useful tool to evaluate and predict release profiles of polymer coated ion-exchange resin complexes.

Algorithms↗

PubMed2006

Investigation of genetic association between human Frizzled homolog 3 gene (FZD3) and schizophrenia: results in a Korean population and evidence from meta-analysis.

The neurodevelopmental hypothesis offers a promising approach through which to explore the pathogenesis of schizophrenia. Human Frizzled-3 protein is one of the major components of the Wnt signaling pathway and plays a crucial role in regulating early neurodevelopmental processes. Therefore, the human Frizzled homolog 3 (FZD3) gene, which encodes this protein, may be an excellent candidate gene for association studies of schizophrenia. To replicate the previously reported positive association between FZD3 and schizophrenia in Han Chinese and Japanese populations, we genotyped two single nucleotide polymorphism (SNP) markers of FZD3 in 241 unrelated schizophrenic patients and 192 control subjects. Fisher's exact test was used to compare the genotypic and allelic frequencies in the two groups. In addition, to integrate and evaluate the accumulated evidence published to date, we performed a meta-analysis on the published data, including our own. No evidence was found to support the association between either of the investigated SNP markers and schizophrenia in a Korean population. Moreover, the meta-analytic result did not support the association between several commonly investigated markers in FZD3 and schizophrenia. Failure to replicate previous positive association results could reflect various theoretical factors. Therefore, other sources of error have to be ruled out before coming to a conclusion. In the case of FZD3, it seems that repeated failures to replicate the original results by several independent research groups combine to provide evidence against an association between FZD3 and schizophrenia. Other candidate genes involved in early neurodevelopmental processes may deserve further investigation.

Alleles↗

PubMed2005

Fast-melting tablets based on highly plastic granules.

Highly plastic granules that can be compressed into tablets at low pressure were developed to make fast-melting tablets (FMTs) by compression method. The highly plastic granules are composed of three components: a plastic material, a material enhancing water penetration, and a wet binder. One of the unique properties of the highly plastic granules is that they maintain a porous structure even after compression into tablets. The porous and plastic nature of the granules allows fast absorption of water into the compressed tablet for fast melting/dissolution of the tablet. The prepared tablets possess tablet strength and friability that are suitable for multi-tablet packages. The three-component highly plastic granules provide an effective way of making FMTs by compression.

Chemistry, Pharmaceutical↗

PubMed2005

Frosta: a new technology for making fast-melting tablets.

The fast-melting tablet (FMT) technology, which is known to be one of the most innovated methods in oral drug delivery systems, is a rapidly growing area of drug delivery. The initial success of the FMT formulation led to the development of various technologies. These technologies, however, still have some limitations. Recently, a new technology called Frosta (Akina) was developed for making FMTs. The Frosta technology utilises the conventional wet granulation process and tablet press for cost-effective production of tablets. The Frosta tablets are mechanically strong with friability of < 1% and are stable in accelerated stability conditions when packaged into a bottle container. They are robust enough to be packaged in multi-tablet vials. Conventional rotary tablet presses can be used for the production of the tablets and no other special instruments are required. Thus, the cost of making FMTs is lower than that of other existing technologies. Depending on the size, Frosta tablets can melt in < 10 s after placing them in the oral cavity for easy swallowing. The Frosta technology is ideal for wide application of FMTs technology to various drug and nutritional formulations.

Administration, Oral↗

PubMed2004

Association study of dopamine transporter gene and schizophrenia in Korean population using multiple single nucleotide polymorphism markers.

Inherited or acquired dysfunction of the dopamine system is believed to underlie the core symptoms of schizophrenia, and there are some evidences that dopamine transporter activity may be altered in schizophrenic patients. Therefore, dopamine transporter gene (DAT1) has been traditionally considered a probable candidate gene for the association study of schizophrenia. Until now, association studies of the dopamine transporter gene (DAT1) with schizophrenia have yielded largely negative results. However, these results cannot be regarded as conclusive in that they were all obtained from just a single marker, that is, 3' untranslated region variable number of tandem repeat (VNTR). We have therefore tried to find other single nucleotide polymorphisms (SNPs) in DAT1 gene and to use them as additional markers for the association study of schizophrenia. Searching for the SNPs had been done with 50 Korean schizophrenic patients. DNA sequences encompassing the whole exon and flanking exon-intron junctions were amplified and searched for the presence of SNPs. Total of five SNPs were found. Among these, three SNPs (1215A>G, 1398C>T, IVS11+14G>A) as well as the 3' untranslated region VNTR were selected as the markers to be genotyped. The allelic and genotypic frequencies of these markers were determined in 252 schizophrenic patients and 271 controls and compared between them. The frequencies of algorithmically derived haplotypes were also compared. No evidence of association was found between any of these markers and schizophrenia. The result using haplotypes was also negative. However, when the patient subgroup with verified familial history and the subgroup with early age of onset were re-analyzed, weak trend of association between 1398C>T SNP marker with schizophrenia was found in both cases. In accordance with the previous literature, we could not find any evidence of association between DAT1 gene and schizophrenia. This result acquired more certainty because not only the VNTR but several SNPs present in DAT1 gene and newly constructed haplotypes were also used as additional markers. However, the finding of weak association between one of the SNP markers (1398C>T) and the specific subgroups of schizophrenia patients added further support to the importance of defining more homogenous subgroups in association studies.

3' Untranslated Regions↗

PubMed2004

Experience of maintaining clozapine medication in patients with 'red-alert zone' neutropenia: long-term follow-up results.

According to the recommended guidelines by Novartis, neutropenia in the range of a white blood cell count less than 3000 per mm, or an absolute neutrophil count (ANC) less than 1500 per mm, is classified as being in the 'red-alert zone' during clozapine treatment. If a patient's blood test result falls into this zone, immediate discontinuation of clozapine is recommended, and reinstitution is prohibited. However, in some patients, it is not entirely feasible to implement this standard guideline because of the lack of effective alternatives to clozapine treatment. Through retrospective chart reviews, five patients who had been maintained on clozapine treatment despite red-alert zone neutropenia were selected. The haematological and clinical courses of these patients were followed for more than 600 days and were compared with those of two control patients who discontinued clozapine due to neutropenia. In all five patients, no additional episodes of neutropenia occurred during the observation period despite continued clozapine treatment. However, three of them maintained a lower neutrophil count for the remaining observation period. Four patients responded favourably to clozapine treatment as judged by Clinical Global Impression score. Given the limitations of a retrospective chart review and the small number of patients, we cannot draw any definite conclusions. However, while the guidelines for the prevention of agranulocytosis should be generally followed, it may be that judicious continuation of clozapine treatment is less risk-prone than previously considered in selected cases where only a few feasible alternatives to clozapine are available. Moreover, there is an apparent necessity to develop new measures or methods that can differentiate between benign neutropenia and that leading to fatal agranulocytosis.

Adult↗

PubMed2004

Application of poly(acrylic acid) superporous hydrogel microparticles as a super-disintegrant in fast-disintegrating tablets.

Poly(acrylic acid) superporous hydrogel (SPH) microparticles possessing a unique porous structure were used as a wicking agent to decrease disintegration time of fast-disintegrating tablets (FDTs). The compression behaviour of poly(acrylic acid) SPH microparticles was evaluated using the Kawakita equation. Effects of various SPH microparticle sizes and a 19-run fractional factorial design were evaluated. The factorial design was based on four factors consisting of ketoprofen, SPH microparticle, filler, and tableting pressure, and each factor contained three levels on the disintegration time and tensile strength of the prepared FDTs. The poly(acrylic acid) SPH microparticles existed in an amorphous state and swelled approximately 80-times in distilled water and 50-times in pH 6.8 0.2 M phosphate buffer. The compressibility of SPH microparticles increased significantly as the microparticle size increased. The FDTs made of SPH microparticles in the range of 75-106 microm showed the fastest disintegration time and higher tensile strength. SPH microparticle, tableting pressure and ketoprofen had significant effects on disintegration time and tensile strength of ketoprofen FDTs. The FDTs that were prepared with 2.5% w/w SPH microparticles of 75-106 microm at 63 MPa pressure possessed a tensile strength of 84.4 +/- 4.1 N cm(-2) and disintegrated in 15.0 +/- 2.0 s. It was concluded that the poly(acrylic acid) SPH microparticles could serve as a good super-disintegrant decreasing the disintegration time of FDTs.

Acrylic Resins↗

PubMed2004

Orally fast disintegrating tablets: developments, technologies, taste-masking and clinical studies.

Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. This review describes various formulations and technologies developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhancing the FDT properties, such as spray-drying, moisture treatment, sintering, and use of sugar-based disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and clinical studies are also discussed.

Chemistry, Pharmaceutical↗

PubMed2002

Metric characteristics of the drug-induced extrapyramidal symptoms scale (DIEPSS): a practical combined rating scale for drug-induced movement disorders.

The metric properties of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) were examined in 182 subjects treated with antipsychotics. Inter-rater reliability, test-retest reliability, and concurrent validity with other rating scales for EPS were high. Four factors were identified and the optimal diagnostic cut-off scores were obtained. These results suggest that the DIEPSS is a reliable and valid multidimensional rating scale.

Adult↗