• YAKHAK HOEJI
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• v.55 no.5
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• pp.411-418
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• 2011

The dissolution test method and an analytical procedure by HPLC were developed and validated for nafronyl oxalate capsules and tramadol hydrochloride capsules. These drugs were not yet characterized by the dissolution specifications in the Korean Pharmaceutical Codex. So, with each reference and test drugs, we did the preliminary and standard experiments based on the Korean Pharmacopeia Guideline of dissolution testing for solid oral dosage forms. The dissolution test for nafronyl oxalate capsules was carried out under sink conditions as follows: dissolution medium phosphate buffer pH 6.8, paddle rotation speed 100 rpm and vessel volume 900 ml. More than 80% of its label amount was released within 30 min in this method. Also the dissolution test for tramadol hydrochloride capsules was carried out under sink conditions as follows: dissolution medium water, paddle rotation speed 50 rpm and vessel volume 900 ml. More than 90% of its label amount was released within 15 min in this method. The dissolution samples were analyzed with a validated HPLC analytical procedure. The analytical methodology showed acceptable values in terms of specificity, linearity, precision and accuracy. The dissolution test methods described above were adequate for the purpose and may be proposed as a pharmacopeial standard to assess the performance of nafronyl oxalate capsules and tramadol hydrochloride capsules. Furthermore, the outcomes of this study were expected to help create an environment where safe and high quality drugs would be distributed on the domestic market making contributions to advancing public health.

• Korean Chemical Engineering Research
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• v.45 no.2
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• pp.166-171
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• 2007

The adsorption behavior of $Pb^{2+}$ was compared between calcium alginate beads and capsules, which have different structures of alginate-gel core beads and liquid core alginate-membrane capsules, respectively. In terms of adsorption kinetics and isotherms, adsorption characteristics depending on pH and hardening time were compared for both adsorbents and also released calcium ion during the adsorption process was monitored. The adsorption of $Pb^{2+}$ on both adsorbents was caused by surface complexation and ion exchange mechanisms, both of which have similar effects on adsorption process regardless of the amount of adsorbed $Pb^{2+}$. The dependence of $Pb^{2+}$ adsorption upon pH was also similar for both adsorbents indicating the existence of similar functional groups on the surface of adsorbents. However, a different $Pb^{2+}$ adsorption behavior was observed considering the adsorption kinetics. The adsorption kinetic of $Pb^{2+}$ on alginate beads was slower than on alginate capsules and the maximum adsorption loading ($Q_{max}$) onto alginate beads was also less than onto alginate capsules by 49%. This drawback of alginate beads compared to capsules were ascribed to a diffusion limitation due to solid gel-core structure of alginate beads.

• 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.

• Bulletin of the Korean Chemical Society
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• v.29 no.4
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• pp.749-754
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• 2008

To increase the solubility of sibutramine freebase, the solid dispersion was prepared using a fluid-bed granulator. The solid dispersion containing sibutramine freebase was characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). After filling the sibutramine solid dispersion in the gelatin hard capsule, we performed in vitro dissolution test, the stability test under accelerated conditions and pharmacokinetic study in beagle dogs. The DSC and XRD data showed that sibutramine solid dispersion would be amorphous state. The dissolution rate of sibutramine solid dispersion was significantly increased about 70% than sibutramine freebase. The stability of sibutramine solid dispersion capsules was equivalent or above to commercial product of sibutramine. In beagle dogs, the sibutramine solid dispersion showed equivalent pharmacokinetic behavior with commercial product of sibutramine hydrochloride. In conclusion, the solid dispersion system provided a possible way to overcome the low solubility of sibutramine freebase, and the sibutramine solid dispersion can be a bioequivalent with the commercial product in humans.

• YAKHAK HOEJI
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• v.54 no.5
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• pp.348-353
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• 2010

The dissolution test method and an analytical procedure by HPLC were developed and validated for viquidil hydrochloride capsules and alibendol tablets. These drugs were not yet characterized by the dissolution specifications in Korean Pharmaceutical Codex. So, with each reference and test drugs, we did the preliminary and standard experiments based on the Korean Pharmacopeia Guideline of dissolution testing for solid oral dosage forms. The dissolution test for viquidil hydrochloride capsules was carried out under sink conditions as follows: dissolution medium water, paddle rotation speed 50 rpm and vessel volume 900 ml. More than 90% of its label amount was released within 30 min in this method. Also the dissolution test for alibendol tablets was carried out under sink conditions as follows: dissolution medium water, paddle rotation speed 100 rpm and vessel volume 900 ml. More than 90% of its label amount was released within 45 min in this method. The dissolution samples were analyzed with a precise and accurate HPLC method. The developed dissolution test showed specificity, linearity, precision and accuracy within the acceptable range. The dissolution testing method described above was adequate for the purpose and may be proposed as a pharmacopeial standard to assess the performance of viquidil hydrochloride capsules and alibendol tablets.

• Journal of Pharmaceutical Investigation
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• v.37 no.2
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• pp.119-126
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• 2007

Tablet splitting is used in pharmacy practice to adjust the dose to be administered. However, it also causes several problems such as undesirable effect for sustained release or enteric-coated dosage form, inaccuracy of dose, and pharmacist's safety by splitting hazardous drugs. This study investigated the current status of oral dosage form splitting for patients older than 19 years by analyzing Korea National Health Insurance Claims Database. Out of oral solid drugs prescribed (N=1,486,584) 9.8% of them included tablets (or capsules) split. There were some splitting cases even in sustained release (4.9%), enteric-coated forms (1.3%) and hazardous drugs (2.7%) that were selected by NIOSH (The National Institute for Occupational Safety and Health). The most frequently split drugs were antihistamines, neuropsychotics and steroids. In case of digoxin and warfarin, unit doses in a domestic market were not diverse compared to foreign markets. Guidelines for splitting oral solid dosage forms, approval of diverse doses and conducting dose-response studies for the commonly splitting ingredients on Korean people are needed for the saff and effective use of oral solid drugs.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.191-197
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• 2002

Polymer based physical mixtures or solid dispersions containing solubilizing compositions[OA, tween80 and SLS] were prepared using a spray-dryer. Lovastatin(LOS), simvastatin(SIMS), aceclofenac(AFC) and cisapride(CSP) were selected as poorly water-soluble drugs. Dextrin, poly(vinylalcohol) (PVA), poly(vinylpyrrolidone)(PVP) and polyethylene glycol(PEG) were chosen as solubilizing carriers for solid dispersions. The solid dispersions containing solubilizing compositions without drug were prepared without using organic solvents or tedious changes of formulation compositions. This system could be used to quickly screen the dissolution profiles of poorly water-soluble drugs by simply mixing with drugs thereafter. In case of solid dispersion containing drug, organic solvent systems could be used to solubilize model drugs. The dissolution rates of the drugs were higher when mixed with drug and solid dispersions containing solubilizing compositions. However, solid dispersions of LOS, AFC, and CSP simultaneously containing drug and solubilizing compositions in organic solvent systems were more useful than physical mixtures of drug and solid dispersions without drug except SIMS. Based on solubilizing capability of polymer based physical mixtures in gelatin hard capsules, optimal solid dispersion system of poorly water-soluble drugs could be formulated. However, it should be noted that dissolution rate of poorly water-soluble drugs were highly dependent on drug properties, solubilizing compositions and polymeric carriers.

• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.125-142
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• 2011

Solid dispersion, defined as the dispersion of one or more active ingredient in a carrier or matrix at solid state, is an efficient strategy for improving dissolution of poorly water-soluble drugs for enhancement of their bioavailability. Compared to other conventional formulations such as tablets or capsules, solid dispersion which can be prepared by various methods has many advantages. However, despite numerous studies which have been carried out, limitations for commercializing these products remain to be solved. For example, during the manufacturing process or storage, amorphous form of solid dispersion can be converted into crystalline form. That is, the dissolution rate of solid dispersion would continuously decrease during storage, resulting in a product of no value. To resolve these problems, studies have been conducted on the effects of excipients. In fact, modification of the solid dispersions to overcome these disadvantages has progressed from the first generation to the recent third generation products. In this review, an overview on solid dispersions in general will be given with emphasis on the various manufacturing processes which include the use of polymers and on the stabilization strategies which include methods to prevent crystallization.

• Journal of Pharmaceutical Investigation
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• v.15 no.3
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• pp.130-139
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• 1985

Inclusion compounds of suprofen with ${\alpha}-$ and, ${\beta}-cyclodextrins\;({\alpha}-CyD,\;{\beta}-CyD)$ were studied in comparison with suprofen alone and commercial suprofen capsules. Inclusion compound formations of suprofen with ${\alpha}-$, and ${\beta}-CyDs$ in aqueous solution and in solid state were confirmed by UV absorption, circular dichroism spectroscopies, IR spectroscopy, differential scanning calorimetry and X-ray diffraction measurements. Solid inclusion complexes were prepared by freeze-drying method, and their molar ratios were found to be 1 : 1. The dissolution rate of inclusion complexes of suprofen with CyDs was notably higher than that of suprofen alone.

• YAKHAK HOEJI
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• v.59 no.2
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• pp.70-76
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• 2015

A Softgel is an oral dosage form for medicine similar to capsules and softgel dosage form offers several advantages over other oral dosage forms, such as delivering a liquid matrix designed to solubilize and improve the oral bioavailability of a poorly soluble compound as a unit dose solid dosage form, delivering low and ultra-low doses of a compound. This study aimed to qualify a proprietary vegetable soft capsule which contains modified starch and carrageenan as capsule shell components compare to the conventional gelatin softgel. Four kinds of samples were prepared with vegetable and gelatin capsule shell, respectively. Morphology of capsule shell, mechanical strength of capsule, and hygroscopic properties were studied for comparing the quality attributes of softgel. Short-term stability against heat and moisture was also investigated in this study. Vegetable capsule shell showed better mechanical strength, physical stability and disintegration time for temperature and humidity than those of conventional gelatin capsule shell with four different filling materials used frequently as soft capsule form. Conclusively, this vegetable capsule shell polymer system can replace easily gelatin-shell systems and additionally allows encapsulation of lipid fills at high temperatures that are semisolid or solid-like at room temperature.