• Archives of Pharmacal Research
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• 제21권6호
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• pp.645-650
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• 1998

The dual drug-loaded alginate beads simultaneously containing drug in inner and outer layers were prepared by dropping plain (single-layered) alginate beads into $CaCl_2$ solution. The release characteristics were evaluated in simulated gastric fluid for 2 h followed by intestinal fluids thereafter for 12 h. The surface morphology and cross section of dual drug-loaded alginate beads was also investigated using scanning electron microscope (SEM). The poorlv water-soluble ibuprofen was chosen as a model drug. The surface of single-layered and dual drug-loaded alginate beads showed very crude and roughness, showing aggregated particles, surface cracks and rough crystals. The thickness of dual drug-loaded alginate beads surrounded by outer layer was ranged from about 57 to 329mcm. The distinct chasm between inner and outer layers was also observed. In case of single-layered alginate bead, the drug was not released in gastric fluid but was largely released in intestinal fluid. However, the release rate decreased as the reinforcing $Eudragit^{\circledR}$ polymer contents increased. When the plasticizers were added into polymer, the release rate largely decreased. The release rate of dual drug-loaded alginate beads was stable in gastric fluid for 2 h but largely increased when switched in intestinal fluid. The drug linearly released for 4 h followed by another linear release thereafter, showing a distinct biphasic release characteristics. There was a difference in the release profiles between single-layered and dual drug-loaded alginate beads due to their structural shape. However, this biphasic release profiles were modified by varying formulation compositions of inner and outer layer of alginate beads. The release rate of dual drug-loaded alginate beads slightly decreased when the outer layer was reinforced with $Eudragit^{\circledR}$ RS1OO polymers. In case of dual drug-loaded alginate beads with polymer-reinforced outer layer only, the initial amount of druc released was low but the initial release rate (slope) was higher due to more swellable inner cores when compared to polymer-reinforced inner cores. The current dual drug-loaded alginate beads may be used to deliver the drugs in a time dependent manner.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.292.1-292.1
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• 2003

Purpose. To develop a new heterodisperse 650mg acetaminophen HPMC matrix tablet with biphasic sustained release profiles. Methods. Hydroxypropylmethylcellulose(HPMC) matrix tablets were prepared by wet-granulating drug with other excipients, followed by direct compression of the dried granule mixtures into tablet using a rotary tablet machine. (omitted)

• Macromolecular Research
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• 제11권4호
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• pp.283-290
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• 2003

Organic drugs including aspirin, omeprazole, and naproxen with three different levels of octanol/water partition coefficient were examined for their release behavior from the amphiphilic PCL-b-PEO-b-PCL (PCEC) matrix. Scanning electron micrograph (SEM) of PCEC illustrated a well defined two-phase morphology consisted of dispersed poly(ethylene oxide) (PEO) domain and continuous polycaprolactone (PCL) phase. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) experiments veri tied that three model drugs are dissolved as a molecular dispersion in PCEC matrix. The release of hydrophilic aspirin closely followed the water absorption profile of the matrix indicating that its major fraction is present in PEO domain. However, substantial amount of aspirin present in less hydrophilic region displayed discontinuous biphasic release pattern. In the case of omeprazole with intermediate hydrophobicity consistent release behavior was observed for a period of 24 hrs after the rapid liberation of ca. 10% of the drug presumably partitioned in PEO phase. It was ascribed to the fact that the progressive hydration of PCEC matrix gradually increased the chance of drug/water exposure to compensate the exhaustion of device. Naproxen with the highest octanol/water distribution coefficient among three model drugs exhibited a limited release of 35% for 24 hrs. Finally, hydroxypropyl methylcellulose phthalate (HPMCP)/PCEC blend matrix demonstrated an accelerated and quantitative release of hydrophobic naproxen by generating high porosity and thereby expanding polymer/water interface.

• 폴리머
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• 제25권3호
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• pp.334-342
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• 2001

항생제의 서방형 전달을 위해 황산겐타마이신 gentamicin sulfate (GS)을 함유한 poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) 제형을 제조하였다. 본 연구에서는 제형의 두께, hydroxyvalerate (HV) 농도, 초기 약물함유량 및 첨가제의 함유에 따른 약물 방출거동의 변화를 조사하였다. 전자주사현미경을 이용하여 제형의 표면형태와 매트릭스 내부 약물의 조성을 관찰한 결과 약물방출 전과 후 모두 거칠고 다공성인 형태를 가짐을 알 수 있었다. 또한, HV와 첨가제의 함량이 증가할수록 약물이 고분자 매트릭스에 더 조밀하게 배열함을 관찰하였고, 이러한 구조가 약물의 방출에 영향을 미침을 알았다. HPLC를 이용하여 약물의 방출량을 측정한 결과, 모든 제형이 복합적인 방출 방향을 나타내었고, 일부 매트릭스는 30일 동안 거의 영차에 가까운 방출거동을 보였다. 이상의 결과에서 우리는 제형의 두께, 고분자 매트릭스의 조성, 첨가제의 함유량 등을 조절함으로 약물 방출을 제어할 수 있음을 확인하였다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.23-31
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• 2001

MBST at 4hr and SST at 3hr after oral administration remarkably inhibited histamine release from rat mast cells in a dose-dependent manner. MBST treated GPs failed to show biphasic phenomena which indicated to reduce nasal volume as leukotriene antagonists. Both groups of patients who took MBST and SST for 1 week or 2weeks showed significant decreased symptom severity index(SSI) from treatment week 2(p<0.05). The percent volume change after challenge of the antigen was decreased in patients took the extracts for tweets. We abstained longer suppression of the symptom than antihistamine.

• Macromolecular Research
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• 제10권5호
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• pp.246-252
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• 2002

In order to the development of the delivery device of long-acting local anesthetics for postoperative analgesia and control of chronic pain of cancer patient, fentnyl-loaded poly (L-lactide-co-glycolido) (PLGA, molecular weight, 5,000 g/mole; 50 : 50 mole ratio by lactide to glycolide) microspheres (FMS) were studied. FMS were prepared by an emulsion solvent-evaporation method. The influence of several preparation parameters such as initial drug loading, PLGA concentration, emulsifier concentration, oil phase volume, and fabrication temperature has been investigated on the fentanyl release profiles. Generally, the drug showed the biphasic release patterns, with an initial diffusion followed by a lag period before the onset of the degradation phase, but there was no lag time in our system. Fentanyl was slowly released from FMS over 10 days in vitro with a quasi-zero order property. The release rate increased with increasing drug loading as well as decreasing polymer concentration with relatively small initial burst effect. From the results, FMS may be a good formulation to deliver the anesthetic for the treatment of chronic pain.

• Macromolecular Research
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• 제17권7호
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• pp.464-468
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• 2009

Gelatin nanoparticles derived from bovine or porcine have been developed as various types of drug delivery system, and they need to be cross-linked to maintain their physicochemical properties in aqueous environments. Although gelatin is a widely used material in pharmaceutical industries, the safety issue of animal-origin gelatins, such as transmissible mad cow disease and anaphylaxis, remains to be solved. The purpose of this study was to prepare type A gelatin (GA) nanoparticles by modified, two-step, desolvation method and compare the toxicity of the resulting GA nanoparticles with recombinant human gelatin (rHG) nanoparticles. The GA nanoparticles were characterized, and drug loading and release pattern were measured. FITC-BSA, a model protein, was efficiently loaded in the nanoparticles and then released in a biphasic and sustained release pattern without an initial burst. In particular, the cell viability of the GA nanoparticles was less than that of the rHG nanoparticles. This finding suggests that rHG nanoparticles should be considered as an alternative to animal-origin gelatin nanoparticles in order to minimize the safety problems.

• 폴리머
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• 제25권6호
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• pp.884-892
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• 2001

고혈압 치료제로 사용되는 니페디핀을 지속적으로 방출하는 제형을 제조하기 위하여 poly(L-lactide-co-glycolide) 글리코리드와 랙티드의 몰비 50: 50, 분자량:5000 g/mole)를 이용하여 직접 압축성형 방법으로 생분해성 웨이퍼를 제조하였다. 약물과 고분자의 함량비, 웨이퍼의 두께, 하이드록실 메틸셀룰로오스 (HPMC) 함유량 등을 조절하여 PLGA 웨이퍼를 제조하였고, 이들의 형태학적 특성과 방출거동 및 분해거동을 조사하였다. 제조된 웨이퍼는 11일동안 영차의 안정한 방출거동을 보였고, HPMC를 첨가함으로써 초기 방출거동을 제어하는 등 조건을 달리함으로써 방출거동을 조절할 수 있었다. 수분흡수율과 무게변화를 조사한 결과, 방출 실험 4일부터 웨이퍼의 무게 감소가 현저하게 발생하였고, 방출이 완료된 후에는 무게가 약 40% 감소하였다. 이러한 약물전달 시스템은 압축성형방법에 의해 제조하므로 제조가 간단하고, 약물방출 속도를 정확하게 제어할 수 있으므로 이식을 위한 제형으로 제조시 유용하게 쓰일 것으로 예상되었다.

• International Journal of Oral Biology
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• 제31권4호
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• pp.127-133
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• 2006

[ $H_2O_2$ ], a member of reactive oxygen species (ROS), is known to be involved in the mediation of physiological functions in a variety of cell types. However, little has been known about the physiological role of $H_2O_2$ in exocrine cells. Therefore, in the present study, the effect of $H_2O_2$ on cholecystokinin (CCK)-evoked $Ca^{2+}$ mobilization and amylase release was investigated in rat pancreatic acinar cells. Stimulation of the acinar cells with sulfated octapeptide form of CCK (CCK-8S) induced biphasic increase in amylase release. Addition of $30\;{\mu}M\;H_2O_2$ enhanced amylase release caused by 10 pM CCK-8S, but inhibited the amylase release induced by CCK-8S at concentrations higher than 100 pM. An ROS scavenger, $10\;{\mu}M$ Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, increased amylase release caused by CCK-8S at concentrations higher than 100 pM, although lower concentrations of CCK-8S-induced amylase release was not affected. To examine whether the effect of $H_2O_2$ on CCK-8S-induced amylase release was exerted via modulation of intracellular $Ca^{2+}$ signaling, we measured the changes in intracellular $Ca^{2+}$ concentration $([Ca^{2+}]_i)$ in fura-2 loaded acinar cells. Although $30\;{\mu}M\;H_2O_2$ did not induce any increase in $[Ca^{2+}]_i$ by itself, it increased the frequency and amplitude of $[Ca^{2+}]_i$ oscillations caused by 10 pM CCK-8S. However, $30\;{\mu}M\;H_2O_2$ had little effect on 1 nM CCK-8S-induced increase in $[Ca^{2+}]_i$. ROS scavenger, 1 mM N-acetylcysteine, did not affect $[Ca^{2+}]_i$ changes induced by 10 pM or 1 nM CCK-8S. Therefore, it was concluded that $30\;{\mu}M\;H_2O_2$ enhanced low concentration of CCK-8S-induced amylase release probably by increasing $[Ca^{2+}]_i$ oscillations while it inhibited high concentration of CCK-8S-induced amylase release.

• Biomolecules & Therapeutics
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• 제19권4호
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• pp.445-450
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• 2011

Preciously, we demonstrated that a novel NHE-1 inhibitor, KR-33028 attenuated cortical neuronal apoptosis induced by glutamate. In the present study, we investigated the signaling mechanism of neuroprotective effect of KR-33028 against glutamate-induced neuronal apoptosis, especially focusing on mitochondrial death pathway. Our data showed that glutamate induces a biphasic rise in mitochondrial $Ca^{2+}$ and that KR-33028 significantly prevents the second phase increase, but not the first phase increase in mitochondrial $Ca^{2+}$. Furthermore, KR-33028 restored the ${\Delta}{\Psi}_m$ dissipation and cytochrome c release into cytoplasm induced by glutamate in a concentration-dependent manner. The inhibition of mitochondrial $Ca^{2+}$ overload by ruthenium red also inhibited glutamate-induced apoptotic cell death, mitochondrial membrane potential, ${\Delta}{\Psi}_m$ dissipation and cytochrome c release. These data suggest that inhibition of mitochondrial $Ca^{2+}$ overload is likely to be attributable to anti-apoptotic effect of KR-33028. Taken together, our results suggest that anti-apoptotic effects of NHE-1 inhibitor, KR-33028 may be mediated through maintenance of mitochondrial function.