• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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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.

• Journal of Pharmaceutical Investigation
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• v.36 no.3
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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.

• Journal of Pharmaceutical Investigation
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• v.38 no.3
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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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• v.39 no.6
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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.

• Journal of the Korean Chemical Society
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• v.62 no.5
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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.

• Polymer(Korea)
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• v.39 no.1
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• pp.33-39
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• 2015

Olmesartan affiliated to biopharmaceutics classification system class 2 is a poorly water soluble drug. For this reason, olmesartan showed a low bioavailability and a lot of difficulties in the process of designing the pharmaceutical formulation. We prepared the solid dispersions of olmesartan. We confirmed the dissolution rate of drug which was prepared by manufacturing. The pharmaceutical formulation of solid dispersions was designed by using PVP as water soluble polymer. We analyzed morphological feature of solid dispersion by employing a scanning electron microscope. Then, the crystalline property of solid dispersion was confirmed through X-ray diffraction and differential scanning calorimeter. Also, the chemical change of solid dispersion was confirmed by the Fourier transform infrared spectroscopy. In vitro dissolution test was used to analyze the dissolution rate of solid dispersion. The prepared solid dissolution olmesartan confirmed the dissolution rate in the pH 1.2. It was compared with olmetec and improved dissolution rate through solid dispersion.