• Proceedings of the Korean Society of Applied Pharmacology
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• 2002.07a
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• pp.205-205
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• 2002

Two formulations of tiropramide {(${\pm}$)${\alpha}$-(benzoylamino)-4-[2-(diethylamino)-ethoxy]-N,N-dipropyl-benzenepropanamide hydrochloride}, an antispasmodic agent, were orally administered to 16 healthy Korean male volunteers by Latin crossover design with the purpose of evaluating bioeqivalence and phamacokinetics of tiropramide. Tiropramide in human plasma was determined by a gas chromatography/nitrogen phosphorus detector. Detection limit of tiropramide was 5 ng/ml. C$\_$max/ values in test and reference formulations were 93.9 ${\pm}$ 54.3 and 96.4 ${\pm}$ 51.6 ng/ml, respectively. AUC$\_$0\longrightarrowlast/ and AUC$\_$0\longrightarrowinf/ were, respectively, 330.7 ${\pm}$ 193.9 and 349.5 ${\pm}$ 205.3 ng.hr/ml for test formulation, 348.9 ${\pm}$ 207.7 and 380.8 ${\pm}$ 239.0 ng.hr/ml for reference formulation. Terminal half-life was 2.3-2.6 hr. Bioavailability differences for C/aub max/ and AUC$\_$0\longrightarrowlast/ were 2.48% and 5.22%, respectively. Minimum detection differences were less than 20% in both C$\_$max/ AUC. Based on this results, two formulations of tiropramide were considered to be bioequivalent

• Archives of Pharmacal Research
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• v.26 no.5
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• pp.416-420
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• 2003

The analytical method of antispasmodic agent tiropramide {$(\pm)\alpha$-(benzoylamino)-4-[2-(diethylamino)ethoxy]-N,N-dipropylbenzenepropanamide hydrochloride} was developed by gas chromatography/nitrogen-phosphorus detector (GC/NPD) in human plasma. Two kinds of tiropramide tablets were orally administered to volunteers by Latin square crossover design, and blood was withdrawn as designed schedule. The plasma of 1 mL was loaded on Sep-pak $C_{18}$ cartridge and eluted with methanol after washing with 30% methanol. The residue dissolved in 100 $\mu$L of methanol after evaporation was analyzed by GC/NPD. Precision (CV%) of intra-day was located within 2.6% and accuracy was less than 9.7%. Inter-day precision was below 8.7% and accuracy was relatively good as less than 14%. Plasma samples obtained from human volunteers were analyzed for the determination of tiropramide concentration by using this method. The method was sensitive, rapid and suitable enough to be applied for pharmacokinetic and bioequivalence studies of tiropramide in human volunteers.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.420.1-420.1
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• 2002

The purposes of this study were to evaluate bioequivalence (BE) using In-transformed pharmacokinetic parameters obtained from two tiropramide HCI products and to develop the analytical methods for the quantitative determination of tiropramide in human serum. In addition. the in vitro dissolution profiles of the two tiropramide HCI products in various dissolution media: pH 1.2, 4.0. 6.8 and water (KP Ⅶ Apparatus II method) were assessed. BE was evaluated in 20 healthy male Korean volunteers in randomized crossover study. (omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.277.2-278
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• 2003

A liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for the determination of tiropramide in human plasma was developed. Tiropramide and internal standard, cisapride were extracted from human plasma with MTBE at basic pH. A reverse-phase LC separation was performed on Luna C8 column with the mixture of acetonitrile-ammonium formate (10 mM, pH 4.5) (5:5, v/v) as mobile phase. (omitted)

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.223.3-224
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• 2002

• Analytical Science and Technology
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• v.14 no.3
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• pp.221-229
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• 2001

The bioequivalence study of two tiropramide products was evaluated in 16 health male volunteers following intra-muscular injection. Test product was Tiram$^{(R)}$ injection (S Pharm. Co, Ltd.) and reference product was Tiropa$^{(R)}$ injection(D Pharm. Co., Ltd.). The drug concentration in plasma was determined by GC/MS for over a period of 8 hours after injection. Analysis of variance reveal that there are no differences in AUC (area under the plasma concentration-time curve from time zero to infinity), Cmax (maximum plasma concentration) and Tmax (time to reach Cmax). The differences of mean AUC, Cmax and Tmax between two products were 0.73, -1.385 and -12.994%, respectively. Minimum detectable differences (%) at ${\alpha}=0.05$ were all less than 20% given as a guideline (10.05, 17.90 and 19.01% for AUC, Cmax and Tmax, respectively). From these results, the two formulations of tiropramide are bioequivalent and thus, may be prescribed interchangeably.

• Biomolecules & Therapeutics
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• v.8 no.3
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• pp.262-268
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• 2000

The bioequivalence of two tiropramide products was evaluated in 18 health male volunteers following oral administration. Test product was Tira $m^{R}$ tablet (Shin Poong SP-102) (Shin Poong Pharm. Co., Ltd.) and reference product was Tirop $a^{R}$ tablet (Dae Woong Pharm. Co., Ltd.) One capsule of the test and reference product containing 100 mg of tropramide.hydrochloride was administered to the volunteers by randomized two period cross-over study (2 $\times$ 2 Latin square method). The drug concentration in plasma was determined by GC/MS for over a period of 12hours after administration. Analysis of variance reveal that there are no differences in AUC (area under the plasma concentration-time curve from time zero to infinity), Cmax (maximum plasma concentration) and Tmax (time to reach Cmax). The differences of mean AUC, Cmax and Tmax between two products were 3.85, 1.47 and -3.6%, respectively. Minimum detectable differences (%) at $\alpha$=0.1 were all less than 20% given as a guideline (18.07, 17.00 and 20.69% for AUC, Cmax and Tmax, respectively). From these results, the two products are bioequivalent.ent.

• YAKHAK HOEJI
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• v.57 no.3
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• pp.205-212
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• 2013

Dissolution test has been performed to control drug quality and to predict in vivo drug release profile of solid dosage forms, so there's a drift towards setting dissolution test instead of disintegration test. However, some solid dosage forms in Korea Pharmaceutical Codex (KPC) are not established the dissolution test yet, so these monographs are necessary to set the specification of dissolution test. In this study, we developed the specification and test method of dissolution test for itopride hydrochloride tablets and tiropramide hydrochloride tablets which are not established the dissolution test yet. According to the "Manual for Guideline Application for Validation of Analytical Procedures" and "Guidelines on Specification of Dissolution test for Oral dosage form" of Korean Pharmacopoeia (KP), we validated and established each development method. Based on the preliminary dissolution profile, we set the dissolution condition(paddle apparatus, pH 1.2 media, 50 rpm). For this condition, we performed the main dissolution test to determine the specification (45 min, 85%). Finally, we validated each analytical method by specificity, linearity, accuracy and precision. These developed methods will be included the next supplement of KPC and also contributed to the quality control of medicines.