Intestinal Absorption Characteristics of Promethazine Hydrochloride in Rat Single-pass Intestinal Perfusion Model / 医药导报

Objective To study the absorption characteristics of promethazine hydrochloride in different parts of rat intestine, provide evidence for the development of new preparation. Methods Rat single-pass intestinal perfusion model was established. By using high performance liquid chromatography (HPLC), 25, 50, 100 μgmL-1 promethazine hydrochloride concentration changing in different parts of the intestine was detected. Through the relevant calculation, the absorption rate constant ( Ka ) , and the apparent absorption coefficient ( Papp ) were obtained. Results With the concentration increase of promethazine hydrochloride in duodenal and ileal segments, the Ka and Papp increased significantly in the same part. Ka was (28.00±0.02)×10-2min-1 and Papp was (9.64±0.22) in the jejunum were the highest when the promethazine hydrochloride concentration was 50 μgmL-1 . As the concentration increased in colon, there were no significant changes in Ka and Papp . Conclusion Promethazine hydrochloride is absorbed in various intestinal segments, most obviously in duodenum and ileum, the absorption order is duodenum>ileum>jejunum>colon. Promethazine hydrochloride is absorbed most in the small intestine, in line with the intestinal absorption characteristics.

Intestinal Absorption Characteristics of Promethazine Hydrochloride in Rat Single-pass Intestinal Perfusion Model / 医药导报

Objective To study the absorption characteristics of promethazine hydrochloride in different parts of rat intestine, provide evidence for the development of new preparation. Methods Rat single-pass intestinal perfusion model was established. By using high performance liquid chromatography (HPLC), 25, 50, 100 μgmL-1 promethazine hydrochloride concentration changing in different parts of the intestine was detected. Through the relevant calculation, the absorption rate constant ( Ka ) , and the apparent absorption coefficient ( Papp ) were obtained. Results With the concentration increase of promethazine hydrochloride in duodenal and ileal segments, the Ka and Papp increased significantly in the same part. Ka was (28.00±0.02)×10-2min-1 and Papp was (9.64±0.22) in the jejunum were the highest when the promethazine hydrochloride concentration was 50 μgmL-1 . As the concentration increased in colon, there were no significant changes in Ka and Papp . Conclusion Promethazine hydrochloride is absorbed in various intestinal segments, most obviously in duodenum and ileum, the absorption order is duodenum>ileum>jejunum>colon. Promethazine hydrochloride is absorbed most in the small intestine, in line with the intestinal absorption characteristics.

Simultaneous determination of four constituents in Compound Kendir Leaves Tablets Ⅰ by HPLC-DAD / 中成药

AIM To establish an HPLC-DAD method for the simultaneous content determination of four constituents in Compound Kendir Leaves Tablets Ⅰ (Apocyni veneti Folium,Chrysanthemi indici Flos,Stephaniae tetrandrae Radix,etc.).METHODS The analysis of 50％ methanol extract of this drug was performed on a 35 ℃ thermostatic Shimadzu VP-ODS column (250 mm × 4.6 mm,5 μm),with the mobile phase comprising of methanol-0.5％ phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 260 nm and 325 nm.RESULTS Chlorogenic acid,hydrochlorothiazide,buddleodide and promethazine hydrochloride showed good linear relationships within the ranges of 24.91-498.2 ng (r =0.999 9),286.33-5 726.7 ng (r =0.999 9),10.04-200.9 ng (r =0.999 9) and 154.80-3 096.1 ng (r =0.999 9),whose average recoveries were 98.3％ (RSD =1.3％),99.1％ (RSD =0.6％),98.5％ (RSD =1.0％) and 99.3％ (RSD =1.2％),respectively.CONCLUSION This simple,accurate and reliable method can be used for the quality control of Compound Kendir Leaves Tablets Ⅰ.

Determination and dissolution of promethazine hydrochloride and caffeine tablets by HPLC / 国际药学研究杂志

Objective To develop a high performance liquid chromatography (HPLC) method for determining the content and dissolution of promethazine hydrochloride and caffeine tablets. Methods Agilent TC C18 column (250 mm×4.6 mm, 5 μm) was used. The mobile phase was methanol-3‰ triethylamine solution (adjusted to pH2.3 with phosphoric acid) (50: 50, v/v) with a flow rate 1.0 ml/min, and the detection wavelengths were set at 250 nm and 272 nm, respectively. The column temperature was 30°C and the injection volume was 20 μl (injection volume of 10 μl for dissolution). Dissolution of tablets was determined by paddle method and the temperature was 37°C, 900 ml pH 1.2 hydrochloric acid solution, acetic acid buffer (pH 4.5), phosphoric acid buffer (pH 6.8) and water were used as dissolution medie at the rotation speed of 50, 75 r/min for selecting dissolution condition. Results The calibration curves were linear within the range of 0.5-100 μg/ml (r=1) for promethazine hydrochloride, and forcaffeine 4-400 μg/ml (r=0.9999), respectively. The detection limit and quantification limit of promethazine hydrochloride were 15 and 40 ng/ml, and caffeine 2 and 10 ng/ ml, respectively. The recoveries of promethazine hydrochloridum and caffeine were (100.04±1.39) % (n=9) and (99.42±1.07) % (n= 9), respectively. And the stability of working solutions was acceptable in 12 h. The method of dissolution tests for the tablet was established with 900 ml pH 1.2 hydrochloric acid solution as dissolution medium, paddle rotation speed of 50 r/min, and dissolution time 30 min. Conclusion The method is convenient, fast, sensitive and reproducible, with good precision, specificity and accuracy. So it can be used for simultaneous determination and dissolution of promethazine hydrochloride and caffeine tablet.

Determination of Promethazine Hydrochloride and Glycyrrhizic Acid in Compound Promethazine and Gly-cyrrhizae Oral solution by HPLC / 中国药师

Objective:To establish an HPLC method for the determination of promethazine hydrochloride and glycyrrhizic acid in compound promethazine and glycyrrhizae oral solution. Methods:A Thermo BDS C18 column(250 mm × 4. 6 mm,5μm)was used with methanol-glacial acetic acid-0. 2 mol·L-1 ammonium acetate solution (58: 1: 41)as the mobile phase. The flow rate was 1. 0 ml· min-1 and the detection wavelength was 250 nm. The column temperature was ambient and the injection volume was 10 μl. Results:There was a good linear relationship within the concentration range of 0. 079 4-0. 317 6 mg · ml-1 ( r =0. 999 9 ) for promethazine hydrochloride and 0. 060 3-0. 241 1 mg · ml-1 ( r =0. 999 9 ) for glycyrrhizic acid. The average recovery was 99. 61% ( RSD =0. 32%, n=9) and 99. 30% (RSD=0. 59%, n=9), respectively. Conclusion: The method is simple, accurate and repeatable, which can be used to control the quality of the preparation.

Simultaneous Determination of Content and Uniformity of Hydrochlorothiazide and Promethazine Hydro-chloride in Compound Kendir Leaves Tablets Ⅰ by HPLC / 中国药师

Objective:To establish a method for the simultaneous determination of content and uniformity of hydrochlorothiazide and promethazine hydrochloride in compound kendir leaves tablets I. Methods:An HPLC-UV wavelength switching method was adopt-ed. The separation was carried out on a YMC-Pack Pro-C18(250 mm × 4. 6 mm,5 μm)column with 0. 06 mol·L-1 potassium phos-phate monobasic solution(adjusting pH to 3. 0 with phosphoric acid )-methanol as the mobile phase with gradient elution. The flow rate was 1. 0 ml·min-1 , the column temperature was set at 35℃. During 0 to13 min, the detection wavelength was 271 nm, and during 13 to 25 min, the detection wavelength was 251nm. The injection volume was 10μl for content determination and 20μl for content uni-formity. Results:The linear range of hydrochlorothiazide and promethazine hydrochloride was 0. 255 9 ~2. 558 9 μg (r=0. 999 9) and 0. 175 1~1. 751 4 μg (r=0. 999 9) with the average recovery of 98. 06%(RSD=0. 64%, n=9)and 99. 61%(RSD=0. 53%, n=9), respectively. Conclusion:The method is simple, rapid, accurate and reproducible, which can provide a scientific basis for the quality control of compound kendir leaves tablets I.

Extended release promethazine HCl using acrylic polymers by freeze-drying and spray-drying techniques: formulation considerations / Liberação prolongada prometazina HCl utilizando polímeros acrílicos por liofilização e técnicas de secagem por aspersão: consideração de formulação

The present study investigated a novel extended release system of promethazine hydrochloride (PHC) with acrylic polymers Eudragit RL100 and Eudragit S100 in different weight ratios (1:1 and 1: 5), and in combination (0.5+1.5), using freeze-drying and spray-drying techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM), as well as solubility and in vitro dissolution studies in 0.1 N HCl (pH 1.2), double-distilled water and phosphate buffer (pH 7.4). Adsorption tests from drug solution to solid polymers were also performed. A selected solid dispersion system was developed into capsule dosage form and evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of spray-dried dispersions were related to increasing amount of polymers, while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RL100 had a greater adsorptive capacity than Eudragit S100, and thus its combination in (0.5+1.5) for S100 and RL 100 exhibited a higher dissolution rate with 97.14 percent drug release for twelve hours. Among different formulations, capsules prepared by combination of acrylic polymers using spray-drying (1:0.5 + 1.5) displayed extended release of drug for twelve hours with 96.87 percent release followed by zero order kinetics (r²= 0.9986).

O presente trabalho compreendeu estudo de um novo sistema de liberação prolongada de cloridrato de prometazina (PHC) com polímeros acrílicos Eudragit RL100 e Eudragit S100 em diferentes proporções em massa (1:1 e 1:5) e em combinação (0,5+1,5), utilizando técnicas de liofilização e de secagem por aspersão As dispersões sólidas foram caracterizadas por espectrofotometria no infravermelho por transformada de Fourier (FT-IR), calorimetria diferencial de varredura (DSC), difratometria de raios X (PXRD), Ressonância Magnética Nuclear (RMN), microscopia eletrônica de varredura (SEM) e, também, por estudos de solubilidade e de dissolução in vitro em HCl 0,1 N (pH 1,2), água bidestilada e tampão fosfato (pH 7,4). Realizaram-se, também, testes de adsorção da solução do fármaco nos polímeros sólidos. Desenvolveu-se sistema de dispersão sólida exclusiva dentro das cápsulas, que foi avaliado por meio de estudos de dissolução in vitro. Relacionou-se o desaparecimento progressivo de picos do fármaco em perfis termotrópicos de dispersões secas por spray à quantidade aumentada de polímero, enquanto os estudos de SEM sugeriram dispersão homogênea do fármaco no polímero. O Eudragit RL100 apresentou maior capacidade de adsorção do que o Eudragit S100 e, dessa forma, a combinação de (0,5+1,5) para S100 e para RL100 mostrou taxa de dissolução maior, com liberação de 94,17 por cento de fármaco em 12 horas. Entre as várias formulações, as cápsulas preparadas pela combinação de polímeros acrílicos utilizando secagem por aspersão (0,5+1,5) apresentou liberação prolongada do fármaco em 12 horas, com 96,78 por cento de liberação, seguindo cinética de ordem zero (r² = 0,9986).