目的建立匹伐他汀鈣片溶出度測(cè)定方法，評(píng)價(jià)國(guó)內(nèi)仿制藥與原研藥溶出曲線的相似性。方法建立高效液相色譜（HPLC）法測(cè)定匹伐他汀鈣片含量，并進(jìn)行專屬性、回收率、精密度、重復(fù)性、穩(wěn)定性等方法學(xué)考察。以原研藥為參比制劑，采用槳法，轉(zhuǎn)速50 r/min，測(cè)定仿制藥與原研藥在4種不同pH溶出介質(zhì)（pH 1.2鹽酸溶液、pH 4.5醋酸鹽緩沖液、pH 6.8磷酸鹽緩沖液、水）中的溶出度，繪制溶出曲線，采用相似因子（f₂）法分析溶出曲線相似性。結(jié)果色譜條件為：色譜柱Diamonsil C₁₈（250 mm×4.6 mm，5 μm），醋酸鹽緩沖液（冰醋酸500 μL、醋酸銨140.6 mg，加水至1 000 mL）-乙腈（15：85）為流動(dòng)相，波長(zhǎng)244 nm。方法學(xué)驗(yàn)證結(jié)果均符合檢測(cè)要求。其中3家仿制藥與原研藥溶出行為基本一致，另外1家仿制藥在水和pH 4.5醋酸鹽緩沖液中均與原研藥溶出曲線不相似。結(jié)論大部分廠家仿制藥體外溶出與原研藥一致。所建HPLC法適用于匹伐他汀鈣片的濃度測(cè)定，可為今后匹伐他汀鈣片溶出度一致性評(píng)價(jià)提供參考。

Objective To establish a method for determination of dissolution curve of pivastatin calcium tablets, and evaluate the similarity of dissolution curve of domestic generic drugs and the original drugs. Methods The concentrations of samples were detected by HPLC. The specificity, recovery, precision, repeatability, stability and other methodological studies were carried out. The paddle method was using for the dissolution process. The rotation speed of paddle was 50 r/min. To determine the dissolution profiles of generic pivastatin calcium tablets and the original product in four dissolution mediums (the pH 1.2 hydrochloric acid solution, the pH 4.5 acetate buffer solution, the pH 6.8 phosphate buffer solution and water). The f₂ factor method was used for analyze the similarity of dissolution curves. Results A Diamonsil C₁₈ column (250 mm×4.6 mm, 5 μm) was used. Mobile phase consisted of a mixture of acetate buffer(acetic acid 500 μL and ammonium acetate 140.6 mg were added to 1 000 mL water)-acetonitrile(15: 85), and UV detection wavelength was 244 nm. The results of methodology validation met the detection requirements. The dissolution profile of three generic tablet were similar to the original tablet in the four dissolution media. The dissolution of the other company's products was inconformity to the innovater drug in the water dissolution media and pH 4.5 acetate buffer solution. Conclusion The in vitro dissolution of some generic drugs was significantly different from the original drug. The HPLC method be appropriate for the determination of the concentration of pivastatin calcium tablets, which can provide a reference for further consistency evaluation of pivastatin calcium tablets.

R927

河北省衛(wèi)健委醫(yī)學(xué)科學(xué)研究課題計(jì)劃（20200916）