• 약학회지
• /
• 제58권3호
• /
• pp.190-199
• /
• 2014

The Korean Pharmaceutical Codex (KPC) analytical method of ambroxol hydrochloride and clenbuterol hydrochloride formulation is complicated and needed to carry out multiple processes during the test. To improve the low efficiency of analytical procedure that makes pharmaceutical laboratory consume much time and high cost to conduct the test of this formulation, this study was performed for simplifying the pretreatment process and optimizing conditions of the HPLC assay. The analytical procedure using HPLC was developed to establish analytical specification for ambroxol hydrochloride and clenbuterol hydrochloride formulations. The newly developed analytical method has good linearity ($R^2$ >0.999), specificity, precision (RSD<1.0%) and the recovery ranges of 98.50~101.84% for ambroxol, 98.29~101.35% for clenbuterol syrup and 98.66~101.71% for clenbuterol tablets. The LOQs were 0.204 ${\mu}g/ml$ for ambroxol, 0.021 ${\mu}g/ml$ for clenbuterol syrup and 0.073 ${\mu}g/ml$ for clenbuterol tablets. The new method was performed with commercially available samples to confirm analytical conditions and validated to be suitable for saving time and cost to control the quality of routine manufactured products. This analytical method will be used for revising the monograph of ambroxol hydrochloride and clenbuterol hydrochloride formulation in next supplement of KPC.

• 약학회지
• /
• 제48권1호
• /
• pp.60-64
• /
• 2004

Near-infrared (NIR) spectroscopy was used to determine rapidly and nondestructively the content of ambroxol in intact ambroxol tablets containing 30 mg (12.5％ m/m nominal concentration) by collecting NIR spectra in range 1100-1750 nm. The laboratory-made samples had 10.3∼15.9％ m/m nominal ambroxol concentration. The measurements were made by reflection using a fiber-optic probe and calibration was carried out by partial least square regression (PLSR) with autoscaling. Model validation was performed by randomly splitting the data set into calibration and validation data set (7 samples as a calibration data set and 5 samples as a validation data set). The developed NIR method gave results comparable to the known values of tablets in a laboratorial manufacturing Process, standard error of calibration (SEC) and standard error of prediction (SEP) being 0.49％ and 0.49％ m/m respectively. The method showed good accuracy and repeatability NIR spectroscopic determination in intact tablets allowed the potential use of real time monitoring for a running production process.

• Tuberculosis and Respiratory Diseases
• /
• 제44권6호
• /
• pp.1296-1307
• /
• 1997

연구배경 : Erdosteine은 만성 기관지염 급성 악화시는 물론 만성 폐색성 기관지염 치료제로 개발된 Thiol 유도체로서 점액조절작용, 항산화작용이 있으며, 특히 위장관 부작용이 거의 없다. 본 연구에서는 현재 유효성 및 안전성이 입증되어 임상에서 많이 처방되고 있는 Ambroxol과의 비교임상연구를 통해 급성 및 만성 기관지염 환자에서 Erdosteine의 임상적 유용성을 알아보고자 하였다. 방 법 : 본 연구는 무작위 이중맹검 비교시험으로서 전향적 연구방법으로 수행되었다. 급 만성 기관지염으로 다량의 객담배출 혹은 객담배출곤란을 주증상으로 하는 80명을 무작위로 할당하여 Erdosteine 투여군에는 1일 2회, 1회 300mg, Ambroxol 투여군에는 1일 2회, 1회 30mg을 총 7일간 투여하였다. 1차 효과평가기준으로는 객담배출횟수, 객담량, 객담배출용이도, 객담점도, 기침정도, 호흡곤란을 포함한 자각증상이 평가되었고, 2차 효과평가기준으로는 동맥혈가스검사, 폐기능검사가 평가되었다. 안전성은 부작용과 임상병리검사로 평가하였다. 총 80명의 환자 중 61명(Erdosteine군 : 31명, Ambroxol군 : 30명)이 본 연구를 종료하였고 19명은 중도 탈락되었다. 결과의 분석은 paired t-test, ANOVA test, multivariate t2-test, Repeated measures analysis of covariance, two sample t-test, Loglinear-Logit model analysis, Fisher's exact test를 이 용하여 유의성을 검정하였다. 결 과 : 1) 두 군간의 환자배정에 있어서 인구학적, 임상적 특징은 차이가 없었다. 2) 동맥혈가스검사, 폐기능검사에서는 두 군간의 차이는 없었고, 자각증상에서는 Erdosteine군은 객담 배출횟수, 객담량, 객담배출용이도, 객담점도, 기침정도, 호흡곤란에서, Ambroxol군은 객담배출횟수, 객담량, 객담배출용이도, 객담점도, 기침정도에서 유의하게 호전을 보였다. 통계적으로 유의하지 않았으나 Erdosteine군이 Ambroxol군에 비해 더 유의하게 호전되는 경향을 보였다($\alpha$=0.05). 3) 혈액학적검사, 혈액화학적검사 및 소변검사에서는 각 군 모두 임상적으로 의미있는 변화는 없었고 두 군간의 차이도 없었으며, 자각증상에서는 Ambroxol군에서만 4명이 연구 종료시까지 부작용이 소실되지 않았고 2명은 연구를 중단하였으나 두 군간의 차이는 없었다. 4) 각 약제의 최종효과평가에서 Erdosteine군은 31명 중 아주좋은효과 11명, 좋은효과 12명, 경도효과 6명, 무효과 2명, 악화 0명이었고 Ambroxol군은 30명 중 아주좋은효과 6명, 좋은효과 14명, 경도 효과 5명, 무효과 4명, 악화 1명이었으며 Erdosteine군이 Ambroxol군에 비해 증상이 개선될 확률이 약 2.5배만큼 높았다 (p<0.05). 결 론 : Erdosteine은 급성 및 만성 기관지염 환자의 치료에 있어 그 효과와 안전성에 있어서 우수한 약물이라고 할 수 있다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제9권6호
• /
• pp.323-326
• /
• 2005

In the present study, we investigated whether ambroxol, S-carboxymethyl-L-cysteine, dextromethorphan and noscapine affect mucin release from airway goblet cells. Confluent primary hamster tracheal surface epithelial cells were metabolically radiolabeled and chased for 30 min in the presence of varying concentrations of the above agents to assess the effects on $^3H$-mucin release. Noscapine stimulated mucin release during 30 min of treatment period in a dose-dependent manner. However, ambroxol, S-carboxymethyl-L-cysteine and dextromethorphan showed no significant effect on mucin release during 30 min of treatment period. We conclude that noscapine can affect mucin release by acting on airway mucin-secreting cells.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.213.2-213.2
• /
• 2003

A simple analytical procedure using FT-NIR for the rapid determination of individual ingredients was evaluated. Direct measurements were made by reflection using a reflectance accessory, by transmittance using tablet accessory and turn table. FT-NIR spectral data were transformed to the first derivative. Partial Least Square Regression(PLSR) was applied to quantify near-infrared (NIR) spectra of 2 ingredients. These calibration models were cross-validated (leave-one-out approach). The prediction ability of the models was evaluated on ambroxol tablets and compared with the real values in manufacturing procedure. (omitted)

• Journal of Pharmaceutical Investigation
• /
• 제41권5호
• /
• pp.309-315
• /
• 2011

A sensitive and specific liquid chromatographic method coupled with tandem mass spectrometry (LC-MS/MS) was developed for the analysis of ambroxol (active moiety of acebrophylline). After acetonitrile precipitation of proteins from plasma samples, ambroxol and the domperidone (internal standard, IS) were eluted on a C18 column. The isocratic mobile phase was consisted of 10 mM ammonium acetate and methanol (10 : 90, v/v), with flow rate at 0.2 mL/min. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z 379.2${\rightarrow}$264.0 and the m/z 426.2${\rightarrow}$175.1 transitions for ambroxol and the IS, respectively. Twenty four healthy Korean male subjects received two capsules (100 mg ${\times}$ 2) of either the test or the reference formulation of acebrophylline HCl in a 2 ${\times}$ 2 crossover study, this was followed by a 1week washout period between either formulation. $AUC_{0-t}$ (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. The 90% confidence intervals for the log transformed data were acceptable range of log 0.8 to log 1.25 (e.g., log 0.8964 - log 0.9910 for $AUC_{0-t}$ log 0.8690 - log 1.0750 for $C_{max}$). The major parameters, $AUC_{0-t}$ and $C_{max}$ met the criteria of Korea Food and Drug Administration for bioequivalence indicating that Acephyll$^{(R)}$ capsule (test) is bioequivalent to Surfolase$^{(R)}$ capsule (reference).

• Journal of Pharmaceutical Investigation
• /
• 제33권3호
• /
• pp.215-221
• /
• 2003

A bioequivalence study of $Ambrect^{TM}$ tablets (Dong Wha Pharm. Ind. Co., Ltd.) to $Mucopect^{TM}$ tablets (Boehringer Ingelheim Korea, Ltd.) was conducted according to the guideline of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korea volunteers received each medicine at the ambroxol hydrochloride dose of 30 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of ambroxol were monitored by a high-performance liquid chromatography for over a period of 24 hours after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 24 hr) was calulated 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 $Ambrect^{TM}/Mucopect^{TM}$ were 0.89-1.01 and 0.89-1.02, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Ambrect^{TM}\;and\;Mucopect^{TM}$ with respect to the rate and extent of absorption.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.213.3-214
• /
• 2002

• Journal of Pharmaceutical Investigation
• /
• 제35권3호
• /
• pp.179-185
• /
• 2005

Acebrophylline is a compound produced by salifying ambroxol with theophylline-7 -acetic acid. After acebrophylline administration, the salt splits into these two components which feature a peculiar pharmacokinetic behavior, an adequate ambroxol and a low theophylline-7-acetic acid serum levels. The purpose of the present study was to evaluate the bioequivalence of two acebrophylline capsules, Surfolase (Hyundai Pharm. lnd. Co., Ltd.) and Burophil (Kuhnil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of ambroxol from the two acebrophylline formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight healthy male subjects, $23.25{\pm}1.43$ years in age and $64.82{\pm}6.77$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two capsules containing 100 mg as acebrophylline were orally administered, blood was taken at predetermined time intervals and the concentrations of ambroxol in serum were determined using HPLC with electrochemical detector (ECD). The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug Surfolase, were -1.64, -3.33 and -0.92% for $AUC_t$, $C_{max}$ and $T_{max}$, 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 1.25 $(e.g., \;log\;0.93{\sim}log\;1.05\;and\;log\;0.88{\sim}log\;1.05$ for $AUC_t$, and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Burophil capsule was bioequivalent to Surfolase capsule.

• 대한유전성대사질환학회지
• /
• 제13권1호
• /
• pp.37-42
• /
• 2013

Gaucher disease is a lysosomal storage disease caused by deficiency of glucocerebrosidase (GBA). This condition is characterized by accumulation of glucocerebrosidase in liver, spleen, lung, skeletal system, and central nervous system. Gaucher disease is the prototype of disease in which efficacy of enzyme replacement therapy has been established. However, because recombinant enzyme is not able to enter the central nervous system, its efficacy is limited to the non-neurological manifestations of Gaucher disease. Importantly, approximately a half of Korean patients with Gaucher disease suffer from neurological manifestations. In addition, Korean Gaucher disease patients exhibit distinct mutation spectrum from those in other populations. Common mutations in Korean patients with Gaucher disease are also associated with neurological phenotype. Therefore, therapeutic strategies tailored to Korean patients were necessary. Interestingly, a chemical chaperone, ambroxol, has been known to increase residual enzymatic activities of the select mutant GBAs encoded by mutations prevalent in Korean patients. One promising aspect of this drug is that it can cross blood-brain barrier, and enhance the enzyme activity in the brain. In vitro study suggested this chemical chaperone as one of new therapeutic agents in Gaucher disease, and a well-designed human trial is required to confirm its efficacy.