• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.67-73
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• 2011

Ion exchange resins can be one of the good carriers for sustained drug release. However, the sustained release may not be enough only with themselves and hence film coating with rate controlling polymers can be applied to have a further effect on the drug release. Due to the environmental and economic issues of organic solvent for the polymer coating, aqueous polymeric systems were selected to develop dosage forms. Among the many aqueous polymeric dispersions for the film coating, EC (ethylcellulose) based polymers such as Aquacoat$^{(R)}$ ECD and Surelease$^{(R)}$ were evaluated.A fluid-bed coating was applied as a processing method. The drug release rate was quite dependent on the coating level so the release rate could be modified easily by changing different levels of the coating. The drug release rate in the Aquacoat$^{(R)}$ coated resin particles was strongly dependent on curing, which is a thermal treatment to make homogeneous films and circumvent drug release changes during storage. After dissolution test using the compressed tablets in which the coated resin particles are contained, inhomogeneous coating and even pores could be observed showing that the mechanical properties of EC were not resistant to granulation and compaction process. However, when tablets were prepared in different batches, the release profiles were almost identical showing the feasibility of the coated resin particle as incorporated into the tablet formulation.

• Journal of Pharmaceutical Investigation
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• v.36 no.4
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• pp.271-276
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• 2006

Felodipine, a calcium-antagonist of dihydropyridine type, is a poorly water soluble drug and has very low bioavailability. As preceding studies, use of solid dispersion systems and surfactants(solubilizers) has been suggested to increase dissolution and to improve bioavailability of felodipine. But in case of solid dispersion systems, large amount of toxic organic solvents should be used and manufacturing process time become longer than conventional process. In case of using surfactants, as time elapsed, decreasing of dissolution rate of felodipine due to crystallization has been reported. In this study, Copovidon as a hydrophilic polymer and $Transcutol^{\circledR}$ as a surfactant were combined to formulations if order to increase dissolution of felodipine and conventional wet granulation process were applied to manufacturing of formulations. The effect of Copovidon and $Transcutol^{\circledR}$ on the dissolution oi felodipine was investigated in-vitro. When Copovidon and $Transcutol^{\circledR}$ used simultaneously, the dissolution rate of felodipine was prominently increased compared with when used separately and the maximum increase in the dissolution of felodipine was 5.8 fold compared to control. This is most probably due to synergy effect by combination of Copovidon and $Transcutol^{\circledR}$. Felodipine sustained release tablets were successfully formulated using several grades of HPMC as a release retarding agent. The stability of felodipine sustained release tablet was evaluated after storage at accelerated condition($40^{\circ}C/75%\;RH$) for 6months in HDPE(High density polyethylene) bottle. Neither significant degradation nor change of dissolution rate for felodipine was observed after 6months. In conclusion, felodipine sustained release tablet was successfully formulated and dissolution of felodipine, poorly water soluble drug, was prominently increased and also stability was guaranteed by using combination system of hydrophilic polymer and surfactant.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.179-189
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• 2000

Clebopride malate(Cm) is a new benzamide drug which has a potent central antidopaminergic activity possessing antiemetic and anxiolytic properties. A purpose of this study was to assess the feasibility of formulating sustained release preparation by dispersing a drug in hydrophilic polymeric matrices and double layered tablets(DLT), using HPMC, carbopol, PEO, PVP/VA and other polymers as a rate controlling barrier. The matrix and DLT showed optimum dissolution pattern up to 8 hours and the contents of polymer were optimized at 30% level in this preparation. After an oral administration in beagle dog, Cm concentration was determined by use of GC-ECD and pharmacokinetic parameters were calculated by Vallner's method. The AUC of DLT showed similar results and the duration of action was increased 55% compared to that of regular release dosage form. The calculated absorption rate effectiveness(ARE) and controlled release effectiveness(CRE) for DLT increased 50% compared to that of matrix, the overall effectiveness(E) of this product appears to be about 70%. in vivo effectiveness test, DLT showed significant differences from control on antiemetic action of Cm. In consequence, it was possible to conclude that double layered tablet might be a good candidate for the sustained release dosage forms.

• Analytical Science and Technology
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• v.30 no.3
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• pp.154-158
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• 2017

The Korean Pharmacopoeia (KP XI), British Pharmacopoeia (BP 2013) and Japanese Pharmacopoeia contain monographs for the quality control of raw fusidate sodium and its formulations using high performance liquid chromatography (HPLC). However, the assay method for the determination of fusidate sodium in commercial tablets is titration which is less specific than HPLC. In this study, we present an alternative HPLC method for quantitation of fusidate sodium in tablets. Method validation was performed to determine linearity, precision, accuracy, system suitability, and robustness. The linearity of calibration curves in the desired concentration range was high ($r^2=0.9999$), while the RSDs for intra- and inter-day precision were 0.25-0.37 % and 0.11-0.60 %, respectively. Accuracies ranged from 99.46-100.85 %. Since the system suitability, intermediate-precision and robustness of the assay were satisfactory, this method will be a valuable addition to the Korean Pharmacopoeia (KP XI).

• Analytical Science and Technology
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• v.30 no.5
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• pp.221-225
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• 2017

Thioctic acid is a vitamin-like antioxidant which is prepared as tablets and injection. The Korean Pharmacopoeia (KP XI) contains monograph for the quality control of raw thioctic acid using ultra-violet visible spectrophotometry and its formulations using high performance liquid chromatography (HPLC). In British Pharmacopoeia 2013 (BP2013), another HPLC method is used for the assay test of thioctic acid material. For the international harmonization, we present an HPLC method for quantitation of thioctic acid in both raw material and tablets. Method validation was performed to determine linearity, precision, accuracy, system suitability, and robustness. The linearity of calibration curves in the desired concentration range was high ($r^2=0.9995$), while the RSDs for intra- and inter-day precision were 0.93 ~ 1.26 % and 1.40 ~ 1.76 %, respectively. Accuracies ranged from 98.13-100.00 %. Since the system suitability, intermediate-precision and robustness of the assay were satisfactory, this method will be a valuable addition to the Korean Pharmacopoeia (KP XI).

• 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 Pharmaceutical Investigation
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• v.23 no.3
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• pp.145-153
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• 1993

Retaining a drug in the stomach by some means is sometimes necessary to extend the G1 absorption time of the drug more than 6-8 hrs. Hydrogel has often been examined for its feasibility as a dosage form, so called platform, that could be retained in the stomach due to its excellent swelling properties in the gastric fluid. In this study, polyvinylpyrrolidone (PVP) hydrogel crosslinked by albumin or acrylated albumin was synthesized in a tablet form and evaluated for its possibility as the platform. The synthesis of the hydrogel was performed by $^{60}Co\;{\gamma}-ray$ irradiation of N-vinyl-2-pyrrolidone (monomer) in the presence of a crosslinking agent: aqueous solution of albumin or acrylated albumin. Synthetic conditions such as radiation dose, dose rate and concentration of crosslinking agent were varied in order to optimize the swelling and mechanical properties of the hydrogels. Degree of swelling of albumin-crosslinked PVP (Al-PVP) was highly dependent on radiation dose, dose rate and albumin concentration: it was decreased as they increased. On the other hand, that of acrylated albumin-crosslinked PVP (Acryl-PVP) was almost independent on them except dose rate: it was decreased as the radiation dose rate increased. The compressive strength of the two hydrogels was decreased as the dose rate increased. Digestion of both PVP in artificial gastric fluid containing pepsin was delayed by the ${\gamma}-ray$ irradiation. In conclusion, Al-PVP and Acry-PVP with diverse swelling and mechanical properties could be obtained by controlling synthetic conditions, mainly the irradiation dose rate.

• YAKHAK HOEJI
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• v.42 no.2
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• pp.187-195
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• 1998

In order to ameliorate disadvantages of buccal ointments and mucoadhesive tablets used for the treatment of aphthosis, a thin mucoadhesive patch containing triamcinolone acetoni de was designed and evaluated for the pharmaceutical properties. The adhesive gel layer consisting of Noveon AA-1, hydroxypropylcellulose-M and ethylcellulose N 100, and the protective gel layer of ethylcellulose N 100, Eudragit RSPO and castor oil have been formulated and various properties such as viscosity of drug gel layer, thickness, in vitro adhesion time, adhesive strength, surface pH, content uniformity and drug release are tested. The mean viscosity of drug-containing gel layer was found to increase with increasing amount of Noveon OAA-1 or hydroxypropylcellulose-M. The optimum formulation showed the thickness of 171 ${\mu}$m, surface pH of 4.6, in vitro adhesion time of 8 hours and adhesive strength of 272.7g/sheet. The drug content of each patch was relatively homogeneous with the value of 273${\pm}$6.77g. Drug release study showed that compared to mucoadhesive tablet, the patch showed a faster drug release. Drug release was delayed by hydroxypropylcellulose-M, but not by ethylcellulose N 100. The patches prepared were nonirritant and the muco adhesion was better than the commercial product (AftachR) on the market. Based on these results, this mucoadhesive patch is expected to be an effective dosage form for the treatment of aphthosis.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.185-190
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• 2002

To improve the solubility of poorly water-soluble drug and to develop a sustained release tablets, the need for the technique, the formation of solid dispersion with polymeric materials that can potentially enhance the dissolution rate and extent of drug absorption was considered in this study. The 1:1, 1:4, and 1:5 solid dispersions were prepared by spray drying method using PVP K30, ethanol and methylene chloride. The dissolution test was carried out at in phosphate buffer solution at $37^{\circ}C$ in 100 rpm. Solid dispersed drugs were examined using differential scanning calorimetry and scanning electron microscopy, wherein it was found that felodipine is amorphous in the PVP K30 solid dispersion. Felodifine SR tablets were prepared by direct compressing the powder mixture composed of solid dispersed felodipine, lactose, Eudragit and magnesium stearate using a single punch press. In order to develop a sustained-release preparation containing solid dispersed felodipine, a comparative dissolution study was done using commercially existing product as control. The dissolution rate of intact felodipine, solid dispersed felodipine and its physical mixture, respectively, were compared by the dissolution rates for 30 minutes. The dissolution rates of felodipine for 30 minutes from 1:1, 1:4, 1:5 PVP K30 solid dispersion were 70%, 78% and 90%. However, dissolution rate offelodipine from the physical mixture was 5% of drug for 30 minutes. Our developed product Felodipine SR Tablet showed dissolution of 17%, 50% and 89% for 1, 4, and 7 hours. This designed oral delivery system is easy to manufacture, and drug releases behavior is highly reproducible and offers advantages over the existing commercial product. The dissolution rate of felodipine was significantly enhanced, following the formation of solid dispersion. The solid dispersion technique with water-soluble polymer could be used to develop a solid dispersed felodipine SR tablet.

• YAKHAK HOEJI
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• v.37 no.5
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• pp.511-519
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• 1993

The short and variabke transit of drug throught GI tracj and the inter-and intra-subject variations of the transit restrict the sustained drug absorption after oral adminstration. These restrictions may be solved by retaining the dosage forms in the stomach. Then the dosage form will act as a platform which releases the drug slowly and makes the GI absorption occur for a long time. In this study, as the platforms, PVP hydrogels were synthesized by chemical and y-irradiation method in the cylindrical test tube. The chemical method means the synthesis of the hydrogel by heating the mixed solution of N-vinyl-2-pyrrolidone [monomer], acrylated albumin [crosslinking agent], 2, 2'-agobis(2-methylpropionitrile) [initiator] and proxyphylline [drug] at $65^{\circ}C$ for 5 hr. The $\gamma$-irradiation method means the synthesis of the hydrogel by irradiation with $^{60}$ Co $\gamma$-ray of the mixed solution of the monomer, acrylated albumin, and flurbiprofen [drug] at room temperature with total 0.2 Mrad for 3 hr. Our intention is to design the hydrogel tablet (diameter : 1.20 cm, thickness : 0.60 cm) which swells in the gastric fluid after oral administration to such a size that passing through the pylorus could be inhibited during the period of drug release. After releasing drug, the hydrogel should be degraded by the enzymeatic digestion in the stomach, or by hydrolysis and eventually solubilized. Thus, in votro tests were performed to examine the factors that affect swelling and drug release from the PVP hydrogels. Experimental results show that the hydrogels swell to a size larger than the diameter of the pylorus(l.3$\pm$0.7 cm) and the hydrogel prepared by the chemical method is digested by pepsin. But the hydrogel prepared by the $\gamma$-irradiation method was not digested by the pepsin and just collapsed with time. Thus, the swelling of the hydrogel synthesized by $\gamma$-irradiation was independent albumin acrylation time and pepsin concentration. But drug content and radiation dose affected the swelling and drug release kinetics of the hydrogel. Drug release from the hydrigels was prolonged up to about 24 hr. Therefore, it was concluded that by adjusting these factors, the albumin-crosslinked PVP hydrogel synthesized by $\gamma$-irradiation method is expected to be retained in the stomach for up to 60hr and be a potential platform of drugs for long-term GI absorption.