• 약학회지
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• 제59권2호
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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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• 제40권2호
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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.

• 한국식품영양학회지
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• 제25권4호
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• pp.1027-1032
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• 2012

본 연구에서는 혈액 내에서의 오메가-3 지방산의 함량 변화를 측정하여 연질 캡슐과 장용성 캡슐의 차이를 검토하였다. Fish oil 중의 EPA와 DHA의 총합의 함량이 62.87 g/100 g으로 대부분을 차지하고 있다. 연질 캡슐의 경우, 제 1시험액(위액)에서는 내부의 지방이 70% 용출된 반면, 장용성의 경우 10% 정도만이 용출되었다. 제 2액(소장액)에서도 6시간까지 50% 정도 용출되어 90분에 50%가 용출된 일반 연질 캡슐과 대조적이었다. 기존에 사용하였던 연질 캡슐의 EPA 및 DHA는 흡수 초기에 장용성 캡슐에 비하여 다소 높은 비율을 보인 반면, 8시간 이후 장용성 캡슐 섭취한 경우 EPA와 DHA의 혈액내 함량이 비율이 증가하는 경향을 보였다. 경구 투여 48시간 후 지방산 조성은 장용성 캡슐에서는 mono-, poly-unsaturated fatty acid 혈액 내의 함량이 다소 높은 경향을 보였으며, saturated fatty acid 함량 역시 다소 높은 경향을 보였다. EPA와 DHA의 함량은 혈액 내에서 각 지방 분획에서의 함량 차이를 정확하게 측정하기 힘들었다. 이상의 결과에 의하면 장용성 캡슐은 위장관을 통과하여 장에서 용출되는 특성 때문에 지속적인 효과를 기대할 수 있을 것으로 추정된다.

• 한국포장학회지
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• 제22권1호
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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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• 제37권4호
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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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• 제24권1호
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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.

• 약학회지
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• 제48권6호
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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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• 제22권1호
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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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• 제34권1호
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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.

• 한국식품영양과학회지
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• 제44권2호
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• pp.260-267
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• 2015

본 연구에서는 장용성 연질캡슐 코팅가소제로서 PEG(polyethylene glycol)의 활용가능성에 대하여 알아보고자 PEG의 분자량 및 첨가 농도에 따른 코팅 품질을 확인하였으며, 기존에 보고된 가소제인 AMG(acetylated monoglyceride)와 triacetin을 사용하여 코팅된 장용성 연질캡슐의 품질 특성을 비교하였다. PEG 분자량(400, 4,000, 6,000)에 따른 코팅 품질에는 큰 차이가 없었으나 PEG 첨가 농도의 경우 고형분 대비 5% PEG를 사용한 코팅에서는 연질캡슐 피막 접착부에서 코팅 필름 갈라짐이 발생하였으며, PEG 첨가량이 낮을수록 인공장액에서의 붕해시간이 연장되고 백색도가 증가하는 결과를 나타내었다. 용출시험에서 용출의 초기 구간(30~90분)에서는 PEG의 용출 속도가 상대적으로 빠른 모습을 나타내었으며, PEG, AMG 및 triacetin 간의 유의적 차이가 일부 시점에서 관찰되었으나 전체적인 용출 양상은 큰 차이를 보이지 않았다. 또한 PEG 코팅에 비해 AMG와 triacetin 코팅의 경우 백색도가 유의적으로 높았고 가속조건인 고온다습한 환경에서 2개월간 보관 후에 코팅 필름이 갈라졌으며, 붕해시험에서 부적합한 결과를 확인하였다. 결론적으로 우수한 물리 화학적 특성으로 의약품 등에 널리 사용되는 첨가제인 PEG는 장용성 연질캡슐 코팅 가소제로서 활용가능성이 충분하다고 판단하였다.