• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.167-172
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• 2001

All-trans retinoic acid (ATRA), vitamin A acid, has been shown to exert anticancer activity in a number of types of cancers, particularly in acute promyelocytic leukaemia (APL). Due to its highly variable bioavailability and induction of its own metabolism after oral treatment, development of parenteral dosage forms are required. However, its poor aqueous solubility and chemical unstability give major drawbacks in parenteral administration. This study was undertaken to investigate a possibility to develop a parenteral formulation of ATRA by employing solid lipid nanoparticle (SLN) as a carrier. By optimizing the production parameters and the composition of SLNs, SLNs with desired mean particle size (<100 nm) as a parenteral dosage form could be produced from trimyristin (as solid lipid), Egg phosphatidylcholine and Tween 80 (as SLN stabilizer). The mean particle size of SLN formulation of ATRA was not changed during storage, suggesting its physical stability. Thermal analysis confirmed that the inner lipid core of SLNs exist at solid state. The mean particle size of ATRA-loaded SLNs was not significantly changed by the lyophilization process. ATRA could be efficiently loaded in SLNs, while maintaining its anticancer activity against HL-60, a well-known APL cell line. Furthermore, by lyophilization, ATRA loaded in SLN could be retained chemically stable during storage. Taken together, our present study demonstrates that physically and chemically stable ATRA formulation adequate for parenteral administration could be obtained by employing SLN technology.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.14 no.12
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• pp.6324-6329
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• 2013

The aim of this study was to prepare and evaluate tablets containing liquid choline alphoscerate, which is capable of being formulated as a solid dosage form by the adsorption of magnesium aluminum silicate. The tablets were prepared with various absorbent to choine alphoscerate ratios. The physical properties and the dissolution rate were investigated. Considering the tabletting and dissolution rate, the formula scontaining 50-75% absorbent were adequate in the tested formulations. The 62.5% absorbent formula showed superior results with the tests of hardness, friability, disintegration time, and the ratio of dissolution area under the curve. Overall, magnesium aluminum silicate can be an alternative additive to a liquid drug.

• Korean Journal of Clinical Pharmacy
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• v.15 no.1
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• pp.27-33
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• 2005

This study was intended to contribute towards the development of proper drug use system for pediatric patients by investigationg problems related to their medication and identifying drugs that need to be developed into low dosage tab-lets or syrups for pediatric use based on our analysis on the prescriptions for pediatric inpatients from 22 hospitals in South Korea on a day of Feb. 2003. The usage rates in the proportion of less than 0.5 and 1 per unit of oral solid formulation were $29.9{\%}$ and $54.3{\%}$ in hospitals with 1000 beds or more, 36.5 and $60.6{\%}$ in hospitals with 500 to less than 1000 beds, $60.8{\%}$ and $81.6{\%}$ in hospitals with less than 500 beds. Of the 63 oral solid formulation products that were used two or more times in the proportion oi less than 0.5 units, 34 products ($54.0{\%}$) were used as such despite the fact that syrups and lower dosage tablets or capsules were available in the market, and 24 products ($38.1{\%}$) so even when syrup formulations were available. Therefore, it would be desirable that pharmacist communities in charge of dispensing identify the most frequently crushed drugs or those that require special attention in choosing dispensing powders or solutions and develop dispensing guidelines that can be adopted by pharmacists in practice. Moreover government-led policies are needed to encourage development and manufacture of the formulations for pediatrics and to correct unsound prescription and dispensing practices such as using crushed forms of certain oral solid formulations although alternative formulations are available in the market.

• Journal of Pharmaceutical Investigation
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• v.34 no.1
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• pp.57-71
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• 2004

The objective of this study was to provide a better understanding of SUPAC-IR and its application in handling postapproval changes to immediate release solid oral dosage forms. Originally, SUPAC-IR was aimed at reducing the regulator burdern of the industry when they were making postapproval changes, but still at maintaining the formulation quality and performance of a drug product. The postapproval changes that were covered under SUPAC-IR included variations in the components ad composition of formulation, the site of manufacturing, batch size, manufacturing equipment, and manufacturing process. The guidance defined levels of changes, based on the likelihood of risk ocurrence and potential impact of postapproval changes upon the safety and efficacy of a drug product I suggested what a type of fing report should be submitted to the FDA for each level of change. Chemist, manufacturing, and control tests to be executed were also recommended for each change level The important tests specified in the guidance included batch release, stability, in vitro dissolution, and in vivo bioequivalence tests. However, there have been strong demands on revising the current SUPAC-IR in order to resolve some issues and to improve its usefulness in evaluating postapproval changes to immediate release solid oral dosage forms. In particular, the rigorous requirement of case C dissolution test and the definition of batch size were challenged by both academia and the industry. A revision work was in progress to reflect these inputs and to expand the utility of SUPAC-IR. As a result of these concerted efforts, an updated 2nd version of SPAC-IR would be likely to be issued ver soon to the public.

• Journal of Pharmaceutical Investigation
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• v.22 no.4
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• pp.281-287
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• 1992

Omeprazole (OMZ) is very unstable in acidic solution, which selectively inhibit the release of the gastric juice in the gastric mucosa, In order to stabilize (OMZ) in oral solid dosage form, the enteric-coated microcapsules and compression-coated OMZ tablets containing lysine or arginine as stabilizer were prepared and their dissolution and stability test were performed. The haif life of OMZ microcapsules containing arginine was 194 days at $30^{\circ}C$ and OMZ was completely released in 60 min. The half-lives of enteric coated and non-coated compression-coated OMZ tablets with lysine were 292 and 95 days at $30^{\circ}C$, respectively. The half-lives of enteric coated and non-coated compression-coated tablets with arginine were 1752 and 293 days at $30^{\circ}C$, respectively, and OMZ were released completely in 20 min in the 2nd fluid of K.P.VI. Consequently, the enteric-coated compression-coated OMZ tablets with arginine as stabilizer provided a good formulation for oral solid dosage form.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.236.1-236.1
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• 2003

Evaluation of solid surface properties is very important for formulation of solid dosage form, specially insoluble drugs. The contact angle of insoluble drugs was measured by the penetration rate into powder bed using Washburn equation and wicking method. From the measured contact angle data, the surface free energy value of pharmaceutical powders ${\gamma}$s was divided and analysized into the polar component, ${\gamma}$s$\^$p/ and the dispersion component, ${\gamma}$s$\^$d/. Furthermore, the data was interpreted for acid part, ${\gamma}$s$\^$+/ and base part, ${\gamma}$s$\^$$\square$/ of surface free energy. (omitted)

• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.75-82
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• 2011

LB71350 is an HIV protease inhibitor with poor aqueous solubility and extensive first pass effect. The purpose of the present study was to test the feasibility of solid dosage form of LB71350 with improved bioavailability utilizing solid dispersion. Three different compositions with varying ratio of (LB71350: Gelucire 44/14: Tween 20) were studied. Capsule filling of these solid dispersion compositions was tested using a semi-automatic capsule filling system. Oral bioavailability in dog was tested. Chemical and physical stability at 4, 25 and $40^{\circ}C$ was monitored by HPLC assay, dissolution test, powder XRD and microscopy. The capsule filling system yielded uniform products of drug loading up to 10%. Oral bioavailability in dog was improved compared to the aqueous suspension of crystalline LB71350. Capsules were chemically stable for up to 6 months at $40^{\circ}C$. However, there were temperature and composition dependent physical changes. Decrease in dissolution rates after storage at $40^{\circ}C$ was due to the polymorphic change. In conclusion, manufacturing process, bioavailability, and physico-chemical stability have been considered to propose a solid dispersion capsule formulation for the HIV protease inhibitor with poor physico-chemical properties. A new less soluble crystalline form identified during the physical stability test warrants further study.

• YAKHAK HOEJI
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• v.39 no.2
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• pp.185-192
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• 1995

Flurbiprofen, one of potent nonsteroidal antiinflammatory drugs, has several systemic side effects due to dose dumping effect following oral administration of its conventional solid dosage forms. To reduce these side effects and to sustain therapeutic concentration of the drug, matrix tablets of flurbiprofen were prepared and evaluated for sustained release from the tablets. The matrix tablets of flurbiprofen were prepared with Eudragit, Pluronic, (anhydrous) lactose and colloidal silicon dioxide employing two different preparation methods, wet granulation and direct compression. The dissolution rates of the tablets were evaluated using KP 2 method. Formulation factors that affected dissolution rates of flurbiprofen were the type and content of Eudragit, the type and content of Pluronic, and the tablet preparation method. Several formulations of the matrix tablets showed dissolution patterns close to the simulated profile using pharmacokinetic parameters of flurbiprofen.

• Korean Journal of Plant Resources
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• v.21 no.1
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• pp.103-109
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• 2008

Nelumbo nucifera root(NNR) is used to clear summerheat(暑熱), bear Yang(陽) upwards and stop bleeding as mentioned in traditional Korean medicine. Also, it has been known that NNR is effective for lowering blood pressure and hyperlipidemia. The rhizome is considered to be nutritive, demulcent, diuretic and cholagogue and is used to treat piles, dyspepsia and diarrhea. An increasingly growing market for nutraceuticals and functional foods has triggered the study on natural sources for nutraceuticals, health foods and functional foods. But rhizome was inconvenient to formulate liquid dosage form(extract) by way of hot water because of its limited storage. Also the majority of the consumers have a complaint against the dosage. The purpose of this study was to develop the functional materials from NNR without side effects. We formulated the solid dosage form viz tablet and granule from the lotus root. Sensory evaluation was performed in terms of smell, taste, color and overall of lotus root and all colored forms(brown, dark brown, light green and yellow) of tablet and granule to evaluate the acceptability of the formulated tablets and granules. In sensory evaluation, among the formulated tablets and granules, light green granules obtained best score overall and yellow tablets showed the overall improved acceptability. In conclusion, lotus rhizome could be recommended as functional food. Further studies to clarify bioactive functions of Nelumbo nucifera in experimental animal model on atopic dermatitis are in progress.

• Journal of Pharmaceutical Investigation
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• v.32 no.4
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• pp.299-303
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• 2002

The oral bioavailability of itraconazole is variable and low in fasting state. This is mainly due to the low solubility of this drug. Bioavailability can be improved by changing the formulation and it is general that the liquid preparations show greater bioavailability than the solid dosage forms such as tablets and capsules do. Benzyl alcohol-water binary mixture showed the excellent solubilizing capacity for itraconazole but the release of the drug from the preparation needs to be enhanced. In this study, various nonionic surfactants and hydrophilic polymers, poloxamers, were screened to investigate their effects on the releasε of itraconazole from the liquid preparations. Poloxamer 407 showed the most enhancing effect on the drug release and the release rate was proportional to thε amount of poloxamer 407 added. A liquid preparation of itraconazole, consisting of benzyl alcohol/water/poloxamer 407 ternary solvent system, releasεd more than 80% of the total drug amount at 5 min and showεd the possibility of a new formulation development.