• 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.

• Journal of Pharmaceutical Investigation
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• v.40 no.2
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• pp.109-115
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• 2010

The purpose of the present study was to evaluate the bioequivalence of two choline alphoscerate soft capsules, Gliatilin soft capsule (Daewoong Pharmaceuticals Co., Ltd.) and Cholicerin soft capsule (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Serum concentrations of choline after oral administration of choline alphoscerate were determined using a validated LC/MS/MS method. This method showed linear response over the concentration range of 0.5-20 ${\mu}g$/mL with correlation coefficient of 0.9999. The lower limit of quantitation using 100 ${\mu}L$ of serum was 0.5 ${\mu}g$/mL which was sensitive enough for pharmacokinetic studies. Thirty six healthy male Korean volunteers received each medicine at the choline alphoscerate dose of 1200 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Blood samples were taken at predetermined time intervals up to 8 hr. $AUC_t$ (the area under the serum concentration-time curve from time 0 to 8 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (the maximum serum drug concentration) and $T_{max}$ (the time to reach $C_{max}$) were compiled from the serum concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters, indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Cholicerin/Gliatilin were log0.9998-log1.1172 and log0.9938-1.0944, respectively. These values were within the acceptable bioequivalence intervals of log0.80-log1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Cholicerin soft capsule and Gliatilin soft capsule are bioequivalent.

• The Korean Journal of Food And Nutrition
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• v.25 no.4
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• pp.1027-1032
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• 2012

We investigate the changes of fatty acids in blood for an evaluation of the effects of soft and enteric coated capsules containing omega 3 fatty acids. Fish oil, which contained 62.87 g/100 g of sum of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), was used as nutracueticals for omega 3 fatty acids. Lipid releasing amount in soft capsule was 70% in stomach condition. However, there was 10% of releasing amount of lipid observed in enteric coated capsule in stomach condition. In intestinal condition, 50% of lipid releasing amount in enteric coated capsule showed until 6 hr, but soft capsule until 90 min. EPA and DHA contents in soft capsule administration showed higher level than those in enteric coated capsule until 8 hr. However, the administration of enteric coated capsule showed higher level of EPA and DHA in blood after 8 hr. After 24 hr, mono-, poly-unsaturated and saturated fatty acids contents with enteric coated capsule showed higher level than those with soft capsule. The enteric coated capsule containing omega 3 fatty acids was expected to sustain omega 3 fatty acids.

• KOREAN JOURNAL OF PACKAGING SCIENCE & TECHNOLOGY
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• v.22 no.1
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• pp.15-23
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• 2016

Gelatin soft capsules, manufactured by the press through package(PTP) process, are widely used in the production of multivitamin dietary supplements and other health functional foods. Gelatin capsules can prevent light and air from having a direct contact with the contents in the capsule, and the nutrients inside the capsules are preserved without any loss. In the present study, on the basis of the results on the safety of gelatin capsules. The parameters investigated included degradation of the capsules before their shelf life, capsule deformation, and changes in specific nutrients. Moisture and heat in the production and storage environments of the capsules caused the gelatin to swell and attach some of the inorganic salts in the vitamin contents. Nutritional component analysis showed that B1, B5, B9, and B12 contents were decreased, while mineral elemental analysis shown calcium, chloride, and zinc compound were found to be infused into the gelatin of the capsule shell.

• Journal of Pharmaceutical Investigation
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• v.37 no.4
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• pp.255-261
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• 2007

A bioequivalence study of $Nimegen^{TM}$ soft capsule (Medica Korea Pharma. Co., Ltd.) to $RoAccutane^{(R)}$ soft capsule (Roche Korea Ind. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Thirty healthy male Korean volunteers received each medicine at the isotretinoin dose of 60 mg in a $2{\times}2$ crossover study. There was one week wash-out period between the doses. Plasma concentrations of isotretinoin were monitored by a high performance liquid chromatography (HPLC) for over a period of 48 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 48 hr) was calculated by the linear trapezoidal rule method. $C_{MAX}$ (maximum plasma drug concentration) and $T_{MAX}$ (time to reach $C_{MAX}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t\;and\;C_{MAX}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{MAX}$ ratio for $Nimegen^{TM}/RoAccutane^{(R)}$ were $log0.860{\sim}log0.98\;and\;log0.85{\sim}log1.00$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. Thus, our study demonstrated the bioequivalence of $Nimegen^{TM}\;and\;RoAccutane^{(R)}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.24 no.1
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• pp.25-28
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• 1994

The previous vitamin assays in soft capsules have been performed only with capsule contents. Since some vitamins, however, could migrate into gelatin layer of the soft capsules, each vitamin of multivitamin soft capsules in the market was analyzed simultaneously in both capsule content and gelatin layer. The results showed that migrations of nicotinamide and pyridoxine hydrochloride into gelatin layer were pronounced, while those of other vitamins were negligible.

• YAKHAK HOEJI
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• v.48 no.6
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• pp.379-383
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• 2004

Biphenyl dimethyl dicarboxylate (DDB) has been used for the treatment of chronic viral hepatitis B and drug-induced hepatitis through the inhibition of lipid peroxidation and c ovalent binding of drug metabolites to lipids of microsomes. The bioequivalence of two DDB products was evaluated according to the guidelines of KFDA. The test product was Hepaphil soft capsule(R) made by KMS Pharm. Co. Containing 3 mg DDB and the reference product was Nissel tablet(R) made by Taerim Pharm. Co. Containing 25 mg DDB. Twenty healthy male subjects, 25.4(22~30) years old and 66.7(54~77)kg, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets or two capsules were orally administered, blood was taken at predetermined time intervals and the concentration of DDB in plasma was determined using a validated HPLC method with UV detector. Two pharmacokinetic parameters, $AUC_t$ and $C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t$ and $C_{max}$ were log 0.91~log1.00 and log 1.05~log 1.15, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Hepaphil soft capsule is bioequivalent to Nissel tablet.

• Journal of Pharmaceutical Investigation
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• v.22 no.1
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• pp.49-54
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• 1992

This study was carried out for the purpose of developing an effective temazepam soft elastic gelatin capsule (softgel) which exhibits an excellent bioavailability and of comparing the rate and extent of absorption of temazepam from the marked elixir and prepared softgel using hydrophilic liquid such as polyethylene glycol 400 as a suspending agent by rotary die method. Both softgel and elixir containing 3 mg of temazepam were given to 7 healthy male New Zealand White rabbits in a single oral dose cross-over study. Plasma temazepam concentrations were measured by HPLC. The mean peak concentrations of temazepam following a single oral dosing as softgel and elixir dosage form were 13.84 and 13.25 ng/ml, respectively. And the mean time to peak concentration was 1.29 hr for the softgel and 1.07 hr for the elixir. There was no significant difference in the extent of drug absorption (AUC) for the two different dosage froms (p>0.05). While the softgel exhibited mean lag time of 0.63 hr, the elixir did not show any lag time. Statistical moment parameters such as the mean residence time and variance of the mean residence time did not differ significantly for the two formulations.

• Journal of Pharmaceutical Investigation
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• v.34 no.1
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• pp.49-55
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• 2004

To develop a aceclofenac soft capsule, four preparations with various solubilizers were prepared and their dissolution test was carried out. Among four preparations tested, a preparation with ethanolamine was selected as a formula of aceclofenac soft capsule (Clanza $S^{TM}$), since it showed the fastεst dissolution rate. Bioequivalence of aceclofenac tablet, $Airtal^{TM}$ (Dae-Woong Pharmaceutical Co., Ltd.) and aceclofenac soft capsule, Clanza $S^{TM}$ (Korea United Pharmaceutical Co., Ltd.) was evaluated according to the guideline of KA Fourteen normal male volunteers (age 20 - 25 years old) were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After oral administration of one tablet or capsule containing 100 mg of aceclofenac, blood was taken at predetermined time intervals and the concentration of aceclofenac in plasma was determined with an HPLC method under UV detector The pharmacokinetic parameters ($C_{max}$ and $AUC_t$) were calculated and ANOVA was utilized for the statistical analysis of parameters using logarithmetically transformed $AUC_t$, $C_{max}$ and $T_{max}$. The results showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between Aral tablet and Clanza soft capsule were 2.89%, 0.18% and 43.0%, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(15) (e.g. log(0.81) -log(1.23) ad log(0.89) -log(1.4)) fo $AUC_t$ and $C_{max}$, respectively. Thus, the criteria of the KFDA guidelines for the equivalence was satisfied, indicating that Clanza $S^{TM}$ soft capsule is bioequivalent to$Airtal^{TM}$ tablet.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.2
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• pp.260-267
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• 2015

We investigated the applicability of polyethylene glycol (PEG) as a plasticizer in enteric-coated soft capsules based on determination of quality characteristics according to molecular weight and concentration of enteric-coating PEG solution. There was no difference according to molecular weight of PEG, whereas a low PEG concentration in the enteric-coating solution was associated with higher whiteness index and slower disintegration time in pH 6.8 media. Brittleness was observed in the coating film at seam areas in 5% PEG enteric-coating solution after 2 weeks of storage at room temperature. The enteric-coating properties of PEG were compared with those of acetylated monoglyceride (AMG) and triacetin, which are enteric-coating plasticizers. Enteric-coated soft capsule containing PEG as a plasticizer showed a lower whiteness index and faster dissolution profile than AMG and triacetin. Moreover, enteric-coated soft capsule containing AMG and triacetin as plasticizers showed coating film brittleness at seam areas after 2 months of accelerated storage [$40^{\circ}C$, relative humidity (RH) 75%] but no difference at room temperature storage ($25^{\circ}C$, RH 60%). The present study suggests that concentration of PEG is important to determine enteric-coating quality, regardless of the molecular weight of PEG. In conclusion, PEG has potential as a plasticizer due to its transparency and storage stability in enteric-coated soft capsules.