• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.308-308
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• 1994

열분석 (DSC, TG/DTA)을 통해 Q-35는 A, B, C의 세가지 다형이 존재함을 알수 있었으며 이중 상대습도에 따른 흡습성의 변화가 적고, 가습에 의해 다형전환이 일어나지 않는 C형이 제제에 유리하다고 사료된다. 또한C형은 분쇄, 연합 및 타정에 의한 다형의 전환이 없었다. Q-35의 용해도는 물, 메탄올, 에탄올에 각각 0.30.3.55,6.31mg/m1 이었으며 PH5이상에서는 급격히 용해도가 감소하고 산성에서는 용해도가 크게 증가하는 양상을 나타냈다. 적층시험, 배합시험을 통해 선정한부형제의 표준 처방 혼합물로 정제를 저조한 결과Q-35의 성형성은 양호하였고 Q-35의 함량이 증가함에 따라 붕해시간이 다소 지 연됨을 알수 있었다. 그러나 Q-35원료는 유동성이 적어 직타법이 적합하지 않았으며, 습식 과립압축법에 따라 저조한 정제의 붕해시간은 5-9분, 15분 후 용출은 91.$\pm$5.0% 이었다. Q-35정제를 4$0^{\circ}C$, 4$0^{\circ}C$ ㆍ 75%RH에서 6개월, 6$0^{\circ}C$에서 3개월 보존후 함량을 측정한 결과 각각 100.0, 98.7, 98.9%이었으며 그밖의 항목에서도 안정한 결과를 얻어 Q-35정제는 온도 및 습도어 안정한 것으로 사료된다. 대량생산 연구결과 Q-35의 결정수가 이탈되지 않도록 건조, 코팅 공정 중 정제의 온도를 5$0^{\circ}C$ 이하로 유지시켰다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.132-132
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• 1995

OMPED의 결합비는 1:1 몰비로 복합체가 형성됨을 확인하였다. 수용액중(pH 7.0)에서 OMP는 분해속도 k=1.542$\times$$10^{-2}$$hr^{-1}$, shelf life=6.81hr 이었고 OMPED는 k=2.088$\times$$10^{-4}$$hr^{-1}$, shelf life=502.8hr이며 중성은 물론 약산성에서 안정하였다. HPMCP로 장용피한 OMPED pellet은 산저항성이 완벽하고 용출속도가 양호하였으며, OMPED 정제에서는 CAP로 코팅한 정제가 가장 큰 AUC값을 나타내었다. Witepsol H-15 기제를 사용한 각 좌제의 생체이용율은 OMPED 좌제가 86.53 $\mu\textrm{g}$ㆍmin/$m\ell$ 로서 OMP 좌제 61.9 $\mu\textrm{g}$ㆍmin/$m\ell$ 및 OMP-$\beta$-CD 좌제 68.8 $\mu\textrm{g}$ㆍmin/$m\ell$이다.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.21 no.3
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• pp.215-222
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• 2020

Metformin is a recommended first-line therapy drug for type 2 diabetes patients. However, compared to other oral antidiabetic drugs (OAD), metformin has a large unit dosage, with bioavailability of 40-60%. This limiting bioavailability is because metformin is absorbed only in the upper gastrointestinal tract as a BCS class 3 drug. Hence, we propose that applying the Gastroretentive Drug Delivery System (GRDDS) and extending drug release time in the stomach will result in improved bioavailability. We selected the swelling type delivery system, as it is considered the most stable gastroretention technology compared to other GRDDSs. We modified the swelling excipient by using a natural swelling excipient to form a swelling tablet made of carrageenan and hydroxypropyl methylcellulose (HPMC). Our results indicate that the swelling complex tablet made of carrageenan and HPMC has a good swelling ability and shows required sustained release in a dissolution pattern. In addition, the carrageenan complex has a better swelling ability than the marketed metformin tablet, as determined by the ratio, (swelling ability)/(excipient weight). Taken together, our results indicate that the carrageenan complex can be developed as a good swelling excipient. Further optimizations are required for the commercialization of the carrageenan complex.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.16 no.11
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• pp.7549-7554
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• 2015

The aim of this study was to develop gastric retentive bi-layered tablet using floating drug delivery technique. Metformin was selected as a model drug due to its narrow absorption window as well as very highly water solubility. These properties of metformin led to be difficult controlling the drug release. The bi-layered tablet was prepared with bi-layered compression machine to minimize interference between floating part and controlling part. The tablet weight, appearance and hardness were evaluated after compression process. The times of 'time to floating' and 'Floating duration' were tested for floating ability and drug release study was also carried out to understand drug release behavior. Furthermore, the drug release of bi-layered tablet was compared with marketed metformin tablet with sustained release pattern (Glucopharge XR$^{(R)}$).The floating ability and drug release behaviors were well controlled by changing amounts of $NaHCO_3$ (floating substance) and hydroxypropyl methylcellulose (HPMC; release control material). Bi-layered tablet had 13s of time to float, over 10h of floating duration and very similar drug release behavior compared with Glucopharge XR$^{(R)}$($f_2$: 89.6). Consequently, the bi-layered tablet with floating ability was successfully prepared and these properties can maximize the efficacy of metformin.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.16 no.11
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• pp.7838-7843
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• 2015

In this study, metformin hydrochloride for first choice of type 2 diabetes patient is administered relatively high dose, 1000 to 2000 mg orally once a day, and had very high water solubility, so it make difficult to swallow tablet to requires high amount of sustained release agent. To overcome these challenges, we used novel metformin salts had relatively low water solubility to minimize sustaining excipient for small size of dosage form. six novel metformin salts were synthesized by making metformin free form under reaction with NaOH and adding acid salts. we confirmed metformin stearate had the lowest water solubility and showed half drug release in dissolution study at 12hour. In conclusion, novel metformin salts had low water solubility can be used to reduce the size of sustained metformin tablet for improving patient compliance.

• KSBB Journal
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• v.19 no.4
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• pp.321-326
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• 2004

Microparticles of an inclusion complex between itraconazole and 2-hydroxypropyl-${\beta}$-cyclodextrin (HP-${\beta}$-CD) were prepared using an environmentally-benign supercritical anti-solvent (SAS) process. In order to evaluate the degree of complexation, the thermal behavior of solid micro particulate complexes was investigated using differential scanning calorimetry. The experimental results obatined for the solubility and dissolution rate of the microparticulate inclusion complexes in a buffer solution of pH 1.2 showed that the complexation of itraconazole with HP-${\beta}$-CD results in a significant increase in the solubility and dissolution rate of itraconazole. For the microparticulate itraconazole/Hp-${\beta}$-CD inclusion complexes prepared by the SAS process, about 80% of itraconazole was found to dissolve in the buffer solution. Our experimental results confirmed that the SAS process is a promising method for the preparation of microparticles of water-insoluble drug/cyclodextrin inclusion complexes.

• Journal of Pharmaceutical Investigation
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• v.18 no.2
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• pp.55-59
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• 1988

The size of furosemide was reduced by the recrystallization method in order to increase the dissolution rate of the drug. Surfactants or hydrophilic polymers were used to suppress the aggregation in the crystal formation-growth process of microparticles by dispersing action. Dissolution rate of microparticles increased remarkably due to the size reduction of microparticle. The particle size decreased with increasing the concentration of the drug and the dispersing agents, i.e., surfactants or hydrophilic polymers. No polymorphic transition occurred during the microcrystallization process, but the habit of crystal formation was altered in the case of anionic surfactant.

• Journal of Pharmaceutical Investigation
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• v.18 no.4
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• pp.181-186
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• 1988

Inclusion complex of sulfamethoxazole with ${\beta}-cyclodextrin$ was prepared by freeze-drying method in molar ratios of 1:1, 1:1.25, 1:1.5 and 1:1.75, and the complex formation was identified by ultraviolet and infrared spectroscopies, powder X-ray diffractometry and differential scanning calorimetry. Dissolution rate and solid state stability of the complex were investigated in comparison with those of sulfamethoxazole powder and the physical mixture of sulfamethoxazole with ${\beta}-cyclodextrin$. As a result, the dissolution rate and the stability of solid complexes in various relative humidity conditions increased more remarkably than those of sulfamethoxazole powder and physical mixture. But the difference according to molar ratio of the complex was not recognized.

• KSBB Journal
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• v.24 no.6
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• pp.533-540
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• 2009

In this work, 5'-nitroindirubinoxime (5'-NIO) has been prepared as solid dispersions using a supercritical aerosol solvent extraction system (ASES) process in order to enhance its water solubility and dissolution rate. Solid dispersions of 5'-NIO and poly(vinyl pyrrolidone) (PVP) were prepared in various weight percent ratios. Three-component solid dispersions consisting of 5'-NIO, PVP, and poloxamer 188 (P188) were also prepared to study the influence of P188 level on their morphology, crystallinity, and dissolution behavior. All samples were prepared at $35^{\circ}C$ and 180 bar using supercritical carbon dioxide. The particle morphology and size of the two-component solid dispersions were found to be nearly spherical and much smaller (100-200 nm) compared with the original 5'-NIO. The morphology of three-component solid dispersions became more agglomerated as the level of P188 increased. The crystallinity of the original 5'-NIO was not observed in the solid dispersions prepared by the ASES process. Faster dissolution rates were observed for the three-componet solid dispersions because the arrangement of ethylene oxide and propylene oxide blocks of the poloxamer 188 enabled the formation of micelles in an aqueous phase.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.187-187
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• 1996

세포질에 존재하는 100 kDa Phospholipase $A_2$(cPLA$_2$)는 인지질의 sn-2 위치의 에스테르결합을 가수분해함으로서 Prostaglandin과 Leukotriene등 Eicosanoids 생합성의 전구체인 아라키돈산과 Platelet activating factor(PAF)를 생합성하는 전구체를 동시에 생성시키는 효소로 염증과 세포손상등에 중요한 역할이 기대된다. 본 효소의 활성화 기전을 규명하고자 하는 최근의 활발한 연구에도 불구하고 불명확한 점이 많은 것이 현실이다. 특히 세포를 자극하였을 때 유리되는 아라키돈산의 증가율과 세포를 파괴한 후 조제한 가용성분획에서 측정한 활성의 증가율과는 많은 차이를 나타냈다. 이러한 결과부터 cPLA$_2$ 효소 자체를 활성화시키는 어떤 인자를 가정하였다. 최근, PLA$_2$의 또다른 형태인 14 kDa의 분비성 PLA$_2$의 in vitro 활성을 증가시키는 인자가 동정되어 그 생화학적 특성이 규명되고 있으나 이 인자는 cPLA$_2$의 활성에는 아무런 증가효과를 나타내지 않았다. 본 연구자들은 소의 뇌조직에서 cPLA$_2$의 활성을 증가시키는 인자를 발견하고 그의 생화학적인 특성을 규명하였다. 돼지 비장에서 정제한 cPLA$_2$를 사용하였으며 소의 뇌 조직의 가용성 분획으로부터 본 활성화 인자를 동정하였으며 그 활성분획을 양이온 크로마토그라피로서 Mono S EPLC와 Superose 12 Sepharose gel filtration 크로마토그라피를 이용하여 더욱 분리한 결과 약 70 kDa과 25 kDa에서 각각 용출되었다. 이렇게 부분정제한 활성은 췌장에서 분리한 group I과 흰주의 group I과 흰주의 혈소판에서 분리한 group II PLA$_2$에 대해서는 아무런 증가효과를 나타내지 않는 반면, cPLA$_2$의 활성만을 약 5배 증가시켰다. 본 활성은 cPLA$_2$ 효소량의 증가에 따라 활성의 증가효과가 정차 감소하므로 화학량적인 반응(Stoichiometric reaction)일 것으로 예상되었다.