• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.155-165
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• 1994

Some mucoadhesive polymers such as hydroxypropylcelluose (HPC) and carbopol-934 (CP) have been employed for the preparation of mucoadhesive polymeric systems, and their physical properties including mucoadhesion, swelling, and drug release were evaluated. A new simple experimental technique that can quantitatively measure the bioadhesive properties of various polymeric systems has been developed by the methods of detachment force test. As the polymeric systems, the discs of freeze-dried HPC/CP solid dispersions were prepared. The mucosa used in these tests were upper, middle, and lower parts of small intestine of male rats weighing $300{\sim}350\;g$. Detachment forces were increased as the mole fraction of CP increased in discs of HPC/CP solid dispersions. In the points of intestinal site dependence of mucoadhesion, the solid dispersions revealed non-specific mucoadhesion to the intestine. Swelling and drug release characteristics of mucoadhesive polymeric systems were studied extensively to find out the feasibility for the oral controlled delivery systems. Swelling ratio, expressed as the final height/initial height, has been determined in various pH buffer solutions. Hydrochlorothiazide (HCT) was employed as a model drug for release study. Apparent swelling and drug release rate constants, $K_s$ and $K_r$ respectively, were obtained from the square-root time plot of either swelling ratio or released amount of drug, particularly for the time periods before reaching the equilibrium. As a result, the swelling ratio of HPC/CP solid dispersions was increased as the weight percentage of CP increased. Similarly, the release of HCT from the solid dispersions was dependent on pH changes and CP contents, resulted in the slower release of HCT with the increases of pH and CP contents.

• Journal of Microbiology and Biotechnology
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• v.25 no.2
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• pp.234-237
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• 2015

In this study, we developed lysosome-alginate beads for application as an oral drug delivery system (ODDS). The beads harboring lysosomes, which have antimicrobial activity, and various concentrations of alginate were characterized and optimized. For application as an ODDS, pH-dependent lysosome-alginate beads were generated, and the level of lysosome release was investigated by using antimicrobial tests. At low pH, lysosomes were not released from the lysosome-alginate beads; however, at neutral pH, similar to the pH in the intestine, lysosome release was confirmed, as determined by a high antimicrobial activity. This study shows the potential of such an ODDS for the in vivo treatment of infection with pathogens.

• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.313-321
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• 1997

Ion exchange resin complexes of famotidine have been prepared by the reaction of famotidine solution with activated ion exchange resins. Complex formation efficiency between famotidine and ion exchange resin was about $80{\sim}90%$ in average, calculated by HPLC determination. Drug release characteristics from the resin complexes were evaluated by the modified percolation method. Famotidine release was dependent on the type of ion exchange resins. In the case of weakly acidic resin complexes, the cumulative released amount of famotidine was more than 90% for 1hr in pH 1.2 buffer solution. However, in the case of strongly acidic resin complexes, it was less than 5% for 3hr in the same medium. Strongly acidic resins revealed some advantages over weakly, acidic resins for overcoming instability of famotidine in gastric juice. In addition, strongly acidic resin complexes showed controlled release of famotidine in pH 6.8 buffer solution, showing the result of about 60 to 70% of drug release for 5hr. After oral administrations of famotidine-resin complexes to rats as dose of 40 mg equivalent/kg, the pharmacokinetic parameters of famotidine were obtained by model independent analysis and compared with those of famotidine solution or suspension. $C_{max}$ of famotidine-resin complex was lower than that of famotidine solution or suspension. MRT, MAT, and MDT of the complexes were greater than those of famotidine solution or suspension. From these results, it was expected that famotidine was released slowly from the complexes and absorbed continuously into systemic circulation. It was recognized that drug release from the complexes was the rate-limiting step in drug absorption, since there were close correlations between in vitro drug release and in vivo pharmacokinetic parameters.

• Carbon letters
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• v.13 no.3
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• pp.173-177
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• 2012

A drug delivery system (DDS) was prepared with a temperature and pH-responsive hydrogel. Poly(vinyl alcohol) (PVA)/poly(acrylic acid) (PAAc)/poly(N-isopropylacrylamide) (PNIPAAm)/multi-walled carbon nanotube (MWCNT) nanocomposites were prepared by radical polymerization for the temperature and pH-responsive hydrogels. MWCNTs were employed to improve both the thermal conductivity and mechanical properties of the PVA/PAAc/PNIPAAm/MWCNT nanocomposite hydrogels. Various amounts of MWCNTs (0, 0.5, 1 and 3 wt%) were added to the nanocomposite hydrogels. PVA/PAAc/PNIPAAm/MWCNT nanocomposite hydrogels were characterized with a scanning electron microscope. The mechanical properties were measured with a universal testing machine. Swelling and releasing properties of nanocomposite hydrogels were investigated at various temperatures and pHs. Temperature and pH-responsive release behavior was found to be dependent on the content of MWCNTs in nanocomposite hydrogels.

• Journal of Pharmaceutical Investigation
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• v.34 no.6
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• pp.471-475
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• 2004

Tamsulosin has been frequently used for the treatment of benign prostatic hyperplasia. To avoid dose-dependent side effects of tamsulosin upon oral administration, the development of sustained-release delivery system is required, that can maintain therapeutic drug levels for a longer period of time. The aim of this study was therefore to formulate sustained-release tamsulosin matrix tablets and assess their formulation variables. We designed enteric coated sustained-release tamsulosin matrices to fulfill above statement. Aqueous microchannels in the enteric film need to be formed in order to obtain tamsulosin release even in an acidic environment such as gastric region. In the sustained-release tamsulosin matrix, low viscosity hydroxypropylmethylcellulose was used as a rate controller. Povidone K30 was also added to the matrices to facilitate water uptake so that a decrease in the release rate of tamsulosin as time elapses was prevented, possibly leading to pseudo zero-order release of the drug. The matrices were enteric-coated with hydroxypropylmethylcellulose phthalate (HPMCP), along with povidone K30 as an aqueous microchannel former. With the aqueous microchannels formed within the enteric film, tamsulosin could be released in an acidic condition. The release of tamsulosin decreased with increasing thickness of HPMCP membrane while the release rates of tamsulosin from those having different HPMCP thickness in pH 7.2 aqueous media were not considerably different, indicating that the enteric film was promptly dissolved at pH 7.2. These results clearly suggest that the sustained-release oral delivery system for tamsulosin could be designed with satisfying drug release profile approved by the KFDA.

• Bulletin of the Korean Chemical Society
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• v.30 no.4
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• pp.931-934
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• 2009

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.1
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• pp.31-39
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• 1998

As it has been reported that the depolarization induced acetylcholine (ACh) release is modulated by activation of presynaptic $A_1$ adenosine heteroreceptor and various lines of evidence suggest the $A_2$ adenosine receptor is present in the hippocampus. The present study was undertaken to delineate the role of adenosine receptors on the hippocampal ACh release. Slices from the rat hippocampus were equilibrated with $[^3H]choline$ and then the release amount of the labelled product, $[^3H]ACh$, which was evoked by electrical stimulation (rectangular pulses, 3 Hz, 2 ms, 24 mA, $5\;V/cm^{-1}$, 2 min), was measured, and the influence of various adenosine receptor-related agents on the evoked tritium outflow was investigated. And also, the drug-receptor binding assay was performed in order to confirm the presence of $A_1$ and $A_2$ adenosine receptors in the rat hippocampus. N-ethylcarboxamidoadenosine (NECA), a potent adenosine receptor agonist with nearly equal affinity at $A_1$ and $A_2$ adenosine receptors, in concentrations ranging from $1{\sim}30\;{\mu}M$, decreased the electrically-evoked $[^3H]ACh$ release in a concentration-dependent manner without affecting the basal rate of release. And the effect of NECA was significantly inhibited by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 2 ${\mu}M$), a selective $A_1$ adenosine receptor antagonist, but was not influenced by 3,7-dimethyl-1-propargylxanthine (DMPX, 5 ${\mu}M$), a specific $A_2$ adenosine receptor antagonist. $N^6-cyclopentyladenosine$ (CPA), a selective $A_1$ adenosine receptor agonist, in doses ranging from 0.1 to 10 ${\mu}M$, reduced evoked $[^3H]ACh$ release in a dose-dependent manner without the change of the basal release. And the effect of CPA was significantly inhibited by 2 ${\mu}M$ DPCPX treatment. 2-P-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680C), a potent $A_2$ adenosine receptor agonist, in concentrations ranging from 0.1 to 10 ${\mu}M$, did not alter the evoked ACh release. In the drug-receptor binding assay, the binding of $[^3H]2-chloro-N^6-cyclopentyladenosine$ ($[^3H]$CCPA) to the $A_1$ adenosine receptor of rat hippocampal membranes was inhibited by CPA ($K_i$ = 1.22 nM), NECA ($K_i=10.17 nM$) and DPCPX ($K_i=161.86 nM$), but not by CGS-21680C ($K_i=2,380 nM$) and DMPX ($K_i=22,367 nM$). However, the specific binding of $[^3H]CGS-21680C$ to the $A_2$ adenosine receptor was not observed. These results suggest that the $A_1$ adenosine heteroreceptor play an important role in evoked ACh release, but the presence of $A_2$ adenosine receptor is not confirmed in this study.

• Journal of Pharmaceutical Investigation
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• v.18 no.1
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• pp.23-30
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• 1988

The sustained-release micropellets containing rifampicin were prepared by spray congealing micropelleting technique using gelatin as the embedding matrix, and hardened by treating with the formalin-isopropanol mixture. Dissolution of rifampicin from micropellets was significantly retarded, and greatly dependent on formalin concentration, hardening time and pH of the dissolution medium. It was found that this prolongation was more distinguished in pH 1.2 dissolution medium rather than pH 7.4, which might be attributed to the swelling characteristics of gelatin used in the dissolution medium. In-vitro dissolution kinetics indicated that the drug release followed the first-order process.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.977-982
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• 2005

The aim of this study was to compare two formulations of film-coated pellets containing c1arithromycin after single oral dose study in healthy male volunteers. Two formulations with different coating polymers were prepared: formulation-1 (F-1) was prepared by incorporating three kinds of pH-dependent gradient-release coated pellets into capsules and formulation-2 (F-2) was prepared by coated with an insoluble semiosmotic film. Release profiles of filmcoated pellets were evaluated using paddle method under different conditions. Pharmacokinetic profiles of these formulations were obtained in three healthy male volunteers and compared to commercially available immediate release (IR) tablets. The relative bioavailability based on the $AUC_{0-24h}$ was found to be $96.2\%\;and\;58.7\%$ for F-1 and F-2 compared with IR, and the $T_{max}$ was delayed.

• KSBB Journal
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• v.31 no.4
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• pp.219-227
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• 2016

Valsartan, a drug for the treatment of cardiovascular disease, exhibited low bioavailability which was caused by, at least in part, limited solubility at low pH. Present investigation deals with the preparation and characterization of gastro-retentive drug delivery system (GRDDS) using valsartan solid dispersion. We prepared solid dispersion using surfactants (Poloxamer 407) and alkalizer ($Na_2CO_3$) which may to be useful for improving solubility of valsartan at low pH and evaluated by saturated solubility of valsartan in distilled water. Valsartan gastro-retentive (GR) tablets containing solid dispersion prepared and evaluated by weight variation, floating time and dissolution rate. Compression at lower pressures resulted in the tablets floating over simulated gastric fluid (pH 1.2) for more than 17 h. In vitro release of valsartan from GR tablet was dependent on the amount of poloxamer 407 and hydroxypropyl methylcellulose. On the basis of evaluation parameter, formulation E-3 was selected as a final formulation. Therefore, it can be concluded that the GR tablets containing solid dispersion may be exploited successfully for the delivery of poorly drug such as valsartan.