• Journal of Pharmaceutical Investigation
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• 제40권spc호
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• pp.1-7
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• 2010

Since the introduction of the biopharmaceutics classification system (BCS) in 1995, it has viewed as an effective tool to categorize drugs in terms of prediction for bioavailability (BA) and bioequivalence (BE). The BCS consist of four drug categories: class I (highly soluble and highly permeable), class II (low soluble and highly permeable), class III (highly soluble and low permeable) and class IV (low soluble and low permeable), and almost all drugs belong to one of these categories. Likewise, classifying drugs into four categories according to their solubility and permeability is simple and relatively not controversial, and thus the FDA adopted the BCS as a science-based approach in establishing a series of regulatory guidance for the industry. Actually, many pharmaceutical companies have gained a lot of benefits, which directly connect to cost loss and failure decrease in the early stage of drug development. Recently, instead of solubility, using dissolution characteristics (e.g. intrinsic dissolution rate) have provided an improvement in the classification in correlating more closely with in vivo drug dissolution rather than solubility by itself. Furthermore, a newly modified-version of BCS, biopharmaceutics drug disposition classification system (BDDCS), which classify drugs into four categories according to solubility and metabolism, has been introduced and gained much attention as a new insight in respect with the drug classification. This report gives a brief overview of the BCS and its implication, and also introduces the recent new trend of drug classification.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.151-157
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• 2002

• Journal of Pharmaceutical Investigation
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• 제36권3호
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• pp.161-167
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• 2006

The objective of this study was to investigate the dissolution patterns of variety of orally administered drug products available on the market. It aimed to understand their dissolution behaviors on the basis of the biopharmaceutics classification system (BCS) concept. On the tenets of BCS, several active pharmaceutical ingredients were selected: fluoxetine hydrochloride (class I), naproxen sodium (class ll), pyridostigmine bromide (class III), furosemide (class IV) and simvastatin (class IV). Typical dissolution media used in this study were pH 1.2, pH 4 & 6.8 phosphate buffers, and water. In cases, particular dissolution media specified in the KP and/or USP were used. Dissolution patterns of fluoxetine hydrochloride and pyridostigmine bromide products were characterized by their rapid release In addition, their dissolution characteristics were relatively unaffected by the type of a dissolution medium. Similar dissolution patterns were observed with pH 1.2, pH 4 & 6.8 phosphate buffers and water. By sharp contrast, poor dissolution patterns were noticed with naproxen sodium products, when pH 1.2 and pH 4 phosphate buffer were used. Improvements in its dissolution were achieved by switching the dissolution media to pH 6.8 phosphate buffer or water. Unsatisfactory dissolution data also were observed with a simvastatin product, when it was subject to dissolution tests by use of a surfactant-free pH 1.2, pH 4 & 6.8 phosphate buffers and water. All the release patterns reported in this study were best understood when BCS concepts were implemented. Our results demonstrated that a BCS-based drug classification should be considered first to choose a dissolution test/method and set up dissolution specification.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.411.3-412
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• 2002

On the basis of recognizing that physicochemical properties (lipophilic/hydrophilic), intestinal absorption clearance and pharmacokinetic characteristics of drug are the fundamental parameters controlling the rate and the extent of drug absorption, the biopharmaceutics classification system for the correlation between drug lipid- solubility and intestinal absorption clearance is proposed. (omitted)

• 약학회지
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• 제44권5호
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• pp.424-431
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• 2000

A biopharmaceutics drug classification system for correlation between in vitro dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling the rate and extent of drug absorption. The objective of this study was to assess whether in vitro dissolution profiles of immediate-release beta-blocker tablets can be correlated with intestinal membrane permeability and/or in vivo bioavailability In vitro dissolution of the beta-blocker tablets was examined using KP VII Apparatus II methods at various pH. Intestinal membrane permeability was determined in vitro using the diffusion chamber method. Bioavailablity parameters were cited from literatures. The dissolution profiles did not accurately represent the in vivo bioavailablity However there were good correlations between intestinal membrane permeability and log P (noctanol/buffer). The correlations obtained in this study indicated that in vitro diffusion chamber method could be used to predict intestinal absorption in vivo.

• Journal of Pharmaceutical Investigation
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• 제38권3호
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• pp.183-189
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• 2008

The present study compared the feasibility of Caco-2 and MDCK cells as an efficient in-vitro model for the drug classification based on Biopharmaceutics Classification System (BCS) as well as an in-vitro model for drug interactions mediated by P-gp inhibition or P-gp induction. Thirteen model drugs were selected to cover BCS Class I{\sim}IV$ and their membrane permeability values were evaluated in both Caco-2 and MDCK cells. P-gp inhibition studies were conducted by using vinblastine and verapamil in MDCK cells. P-gp induction studies were also performed in MDCK cells using rifampin and the P-gp expression level was determined by western blot analysis. Compared to Caco-2 cells, MDCK cells required shorter period of time to culture cells before running the transport study. Both Caco-2 and MDCK cells exhibited the same rank order relationship between in-vitro permeability values and human permeability values of all tested model compounds, implying that those in-vitro models may be useful in the prediction of human permeability (rank order) of new chemical entities at the early drug discovery stage. However, in the case of BCS drug classification, Caco-2 cells appeared to be more suitable than MDCK cells. P-gp induction by rifampin was negligible in MDCK-cells while MDCK cells appeared to be feasible for P-gp inhibition studies. Taken all together, the present study suggests that Caco-2 cells might be more applicable to the BCS drug classification than MDCK-cells, although MDCK cells may provide some advantage in terms of capacity and speed in early ADME screening process.

• Journal of Pharmaceutical Investigation
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• 제39권6호
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• pp.417-422
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• 2009

Budesonide belongs to Class II in the Biopharmaceutics Classification System (BCS) for its high permeability and poor aqueous solubility. The purpose of this study was to improve the solubility and dissolution rate of budesonide using an o/w microemulsion system in order to develop a nasal formulation. Based on the results of the solubility study and pseudo ternary phase diagrams, microemulsions of about 80 nm in mean diameter were formulated using isopropyl myristate and Labrasol$^{(R)}$ as an oil phase and a surfactant, respectively. Solubility of budesonide in the microemulsions increased up to 6.50 mg/mL, which is high enough for a nasal formulation. In vitro release profiles of budesonide significantly increased from the microemulsions compared to that of the budesonide powder. These results suggest that the microemulsions of budesonide could further be developed into a clinically useful nasal formulation.

• 대한화학회지
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• 제62권5호
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• pp.352-357
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• 2018

Celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide) is a cyclooxygenase-2 inhibitor used in the treatment of arthritis, acute pain, and dysmenorrhoea. Celecoxib is a Biopharmaceutics Classification System (BCS) class II compound whose oral bioavailability is highly limited owing to its poor aqueous solubility. Several polymorphs of celecoxib have been identified as Form I, Form II, and Form III with melting points of about $162.8^{\circ}C$, $161.5^{\circ}C$, and $160.8^{\circ}C$, respectively. Form IV was generated from the precipitated suspension in the presence of HPMC (Hydroxypropyl methylcellulose) and Polysorbate 80. A rapid rate of dissolution is useful because the rate of dissolution of a drug typically increases its bioavailability. The aim of this study was to investigate the possibility of production of new crystal form of celecoxib that has higher solubility than Form III. New crystal form of celecoxib (Form A) has been isolated by recrystallization and characterized by differential scanning calorimetry (DSC), thermogravimetric (TG) analysis and powder X-ray diffractometry (PXRD). Form A was dissolved faster than Form III. At 30 minutes, the dissolution of Form A was 97.3%, whereas the dissolution of Form III was 82.2% (p < 0.1). After storage of three months at $20^{\circ}C$, in 24% RH (Relative Humidity), the crystal form was not transformed.

• 폴리머
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• 제39권1호
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• pp.33-39
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• 2015

올메사탄은 BCS 2단계에 해당하는 약물로 물에 잘 녹지 않는 난용성 약물이다. 이런 약물이 낮은 생체이용률과 제형을 설계하는 과정에서 어려움을 주는 원인이 된다. 본 연구에서는 올메사탄을 분무건조법 및 회전용매증 발법을 이용해 고체분산체를 제조하여 제법에 따른 난용성약물의 용출률을 확인하였다. 수용성 고분자로 PVP를 사용하여 약물과 고분자의 비율별로 고체분산체를 제조하였다. SEM을 이용하여 고체분산체의 형태학적인 특성을 분석하였고, 고체분산체의 결정학적 성질은 XRD와 DSC를 통하여 확인하였다. 또한 FTIR을 통해 화학적인 변화를 확인하고, 생체 외 용출거동 실험을 통하여 변화된 용출률을 확인하였다. 제조된 고체분산체는 pH 1.2에서 용출을 확인하였으며, 올메텍과 용출률을 비교하였으며, 분무건조를 통해 약물의 용출률을 향상시킬 수 있다는 것을 확인할 수 있다.