• Journal of Pharmaceutical Investigation
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• v.38 no.5
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• pp.319-323
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• 2008

For transdermal delivery of ceramides, various liposomes formulations were studied and evaluated. Sodium deoxycholate (SDC), Tween 20 and Span 85 were used as edge activators. The skin permeation of ceramides was performed using a Franz cell apparatus with hairless mouse skin. Among edge activators, SDC showed the higher values of deformability index and skin permeation than did others. For optimization of formulations, we varied the ratios of lipids to edge activators and the compositions between phosphatidylcholine (PC) and ceramides. The optimal ratio of lipid to SDC was observed to be 6:1 (w:w) and that of PC and ceramide was 1:1. Our results suggest that the skin permeation of ceramides could be enhanced by optimized deformable formulations of liposomes containing SDC as a major edge activator.

• Journal of Pharmaceutical Investigation
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• v.40 no.4
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• pp.251-254
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• 2010

The formation of acylated peptide impurities in poly(lactide-co-glycolide) (PLGA) formulations is one of the major challenges to the development of successful sustained-release product. Octreotide, synthetic analogue of somatostatin, has been identified to be acylated in PLGA microsphere formulations. The purpose of this study was to investigate the pH effect on the formation of acylated octreotides by PLGA. In the incubation with PLGA in 0.1 M phosphate buffer at pH 7.4, approximately 98% of octreotide adsorbed to PLGA through 14 days and 66.3% of acylated octreotides were produced after 42 days, whereas the interaction of octreotide with PLGA was significantly inhibited in the incubation at pH 4, in which the acylated octreotides were observed to be 9.2% after 42 days. In the interaction study at pH 4.1-7.4, the production of acylated octreotides was demonstrated to be dependent on environmental pH. Below pH 5.0, the acylation of octreotide was significantly inhibited. This study indicates that the pH is the major factor for the formation of acylated octreotide in PLGA formulations.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.90-90
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• 2003

Sample size calculations play an important role in bioequivalence trials. In almost all clinical trials sample size is determined by considering power under the alternative hypothesis. The alternative hypothesis is the hypothesis that we wish to prove with experiments. Hence, in bioequivalence trials the alternative hypothesis is that two formulations are bioequivalent, while the null hypothesis is that the two formulations are not bioequivalent. (omitted)

• Journal of Pharmaceutical Investigation
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• v.37 no.5
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• pp.291-295
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• 2007

Prostaglandin $E_1\;(PGE_1)$ was formulated as two self-microemulsifying drug delivery systems (SMEDDS) composed of Cremophor $EL^{(R)}$ or Cremophor $ELP^{(R)}$ as a surfactant, ethanol as a cosurfactant and Labrafac $CC^{(R)}$ as an oil to develop liquid preparation for the treatment of erectile dysfunction. In pseudo-ternary phase diagram, viscous gel area and microemulsion area were defined. In the measurement of viscosity, the viscosity of two formulations increased gradually upon the addition of water and it decreased from the water contents over 40%. With excessive water, the present systems formed a microemulsion spontaneously. From these results, rte could expect that the present liquid $PGE_1$ SMEDDS formulations might stay within the urethra in the viscous state when contacting the moisture of the urethra and can be easily eliminated by urination. In long-term stability study, we could select one formulation more stable at the shelf storage condition of $4^{\circ}C$.

• Journal of Pharmaceutical Investigation
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• v.29 no.1
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• pp.67-72
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• 1999

A bioequivalence study of the $Kerola^{\circledR}$ intramuscular injections (Dongkwang Pharmaceutical Co., Korea) to the $Tarasyn^{\circledR}$ intramuscular injections (Roche Co., Korea), formulations of ketorolac tromethamine (KTR), was conducted. Sixteen healthy Korean male subjects were received each formulation at the dose of 30 mg as KTR in a $2{\times}2$ crossover study. There was an one-week washout period between the doses. Plasma concentrations of KTR were monitored by a HPLC method. AUC was calculated by the linear trapezoidal method. $C_{max}$ and $T_{max}$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The differences between the formulations in these parameters were all far less than 20% (i.e., 3.65, 2.59 and 4.35% for AUC, $C_{max}$ and $T_{max}$ respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were 12.87, 13.44, 20.62%, for AUC, $C_{max}$ and $T_{max}$, respectively. The 90% confidence intervals for these parameters were also within 20%. These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 1998-86). Therefore, these results indicate that the two formulations of KTR are bioequivalent.

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.226.2-227
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• 2001

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.278.3-279
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• 2000

• Journal of Pharmaceutical Investigation
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• v.39 no.1
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• pp.37-41
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• 2009

The purpose of this study was to compare the efficacy of Lorelin Depot $Injection^{(R)}$ (Dongkook Pharm. Co., LTD) with Lucrin Depot $Injection^{(R)}$ (Abbott) by measuring serum testosterone level in rats. Leuprorelin (leuprolide acetate), which is an active compound for the two formulations, is an LHRH analogue that is used for the treatment of a wide range of sex hormone-related disorders including advanced prostatic cancer, endometriosis and precocious puberty. Lorelin Depot $Injection^{(R)}$ is a micro-encapsulated formulation to suppress testosterone level by releasing leuprorelin continuously for four weeks with a single subcutaneous injection. The comparison study of the efficacy was performed during four weeks, and serum testosterone levels were monitored in the two formulations. The mean serum testosterone levels from the formulations were decreased to that of the castrate range (50 ng/dL or less) after three days after the initial depot injection, and the concentration were remained throughout four weeks' period. There were no significant differences in the $AUC_{0-3day}$ of testosterone and testosterone levels at 3, 7, 14, 21 and 28 days between the two formulations. These results indicate that the two formulations, Lorelin Depot $Injection^{(R)}$ and Lucrin Depot $Injection^{(R)}$, are bioequivalent in terms of the serum testosterone level in rats.

• Journal of Pharmaceutical Investigation
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• v.28 no.3
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• pp.185-191
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• 1998

A bioequivalence study of the Loxipen tablets (Dae Wha Pharmaceutical Co., Korea) to the Loxonin tablets (Dong Hwa Pharmaceutical Co., Korea), formulations of sodium loxoprofen anhydrous 60 mg, was conducted. Sixteen healthy Korean male subjects received each formulation at the dose of 60 mg as sodium loxoprofen anhydrous in a $2{\times}2$ crossover study. There was a 2-week washout period between the dose. Plasma concentrations of loxoprofen were monitored by an HPLC method for over a period of 6 h after each administration. AUC (area under the plasma concentration-time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ $(time\;to\;reach\;C_{max})$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 5.88, 7.81 and 6.09% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were all less than 20% difference in these parameters between the formulations were all over 0.8 (i.e., 15.81, 13.13 and 19.85 for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (i.e., $-16.52{\sim}4.77$, $-16.65{\sim}1,02$ and $-19.45{\sim}7.28%$ for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the 2 formulations of loxoprofen are bioequivalent and, thus, may be prescribed interchangeably.

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.283-288
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• 1998

Lovastatin, one of the potent cholesterol-lowering agents, is an inactive lactone prodrug which is metabolized to its active open acid, lovastatin acid (LVA). Bioequivalence study of two lovastatin preparations, the test drug ($Mevacor^{\circledR}$: Chungwae Pharmaceutical Co., Ltd.) and the reference drug ($Lovaload^{\circledR}$: Chong Kun Dang Pharmaceutical Co., Ltd.), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Fourteen healthy male volunteers, $23.9{\pm}3.9$ years old and $67.6{\pm}8.0$ kg of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 160 mg as lovastatin in a $2{\times}2$ crossover study. Plasma concentrations of lovastatin acid were analysed by HPLC method for 12 hr after administration. The extent of bioavailability was obtained from the plasma concentration-time profiles of total lovastatin acid after alkaline hydrolysis of the plasma samples. By alkaline hydrolysis, trace amounts of unmetabolized lovastatin were converted to lovastatin acid. The $AUC_{0-12hr}$ was calculated by the linear trapezoidal rule method. The $C_{max}$ and $T_{max}$ were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there were no differences in AUC, $C_{max}$, and $T_{max}$ between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 7.07, 5.77 and 1.18% for AUC, $C_{max}$, and $T_{max}$, respectively). Minimum detectable differences(%) between the formulations at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 17.2, 15.1, and 15.9% for AUC, Cmax, and Tmax, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (e.g.. $-5.20{\sim}19.3$, $-5.00{\sim}16.5$, and $-10.2{\sim}12.5%$ for AUC, $C_{max}$, and $T_{max}$, respectively). These results satisfied the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of lovastatin were bioequivalent.