| 摘要: | 崩散劑常常被拿來促進錠劑的崩散，進而提高有效成分的溶離。當錠劑與水分接觸時會分別發生以下的現象：濕潤、水分穿透行為、錠劑膨脹並崩散開來。測量錠劑崩散的動態行為須由錠劑吸水產生膨脹並崩散為止。本研究嘗試將物性測定儀結合吸水系統去測量崩散劑的膨脹力與吸水能力，並為模擬其在口腔內環境，因此限制其供水行為僅由錠劑下方吸取水分。研究中是難溶於水之以利尿劑氫氯苯嗪(Hydrochlorothiazide)當作模式藥物。賦形劑方面選用水不溶性的磷酸二鈣，而實驗用的錠劑皆採直接壓錠法壓製成錠。以Ac-Di-Sol、Primojel和Polyplasdone XL作為本試驗的崩散劑。取錠劑分別在pH 1.2的鹽酸和pH 6.8的磷酸緩衝液，利用物性測定儀搭配吸水裝置來測量對崩散劑濃度的影響和評估崩散劑功效。而研究中並將崩散試驗與溶離試驗做對照。結果顯示，濃度8%Ac-Di-Sol和8%Primojel可以克服酸鹼之間的影響，Polyplasdone XL膨脹力是不受酸鹼影響。但含量高的崩散劑促進崩散的效果不是隨著濃度高而有效，因為水分在穿透錠劑內部受阻，則使得膨脹力增加速率緩慢，不利於促進完整錠劑的崩散作用。另外，供水對於產生膨脹力是一樣很重要的因素，在高濃度時常成為膨脹力產生的決定因素。結論，傳統藥典的崩散溶離規範是無法區別崩散劑的功效與機轉，本研究利用物性測定儀搭配吸水裝置可以分析並區別崩散劑的效果。
The efficiency of disintegrants be in promoting tablet disintegration and increase drug release rate. When the tablet comes in contact with water, the following phenomena, respectively, occur, wetting, water penetration, and tablet disintegration with significant swelling. However, the dynamic approach to tablet disintegration, which is based on the measurement of the force that develops inside the compact upon water entrance, is basically taken up. Therefore, this study try to combine a texture analyzer, which is capable of measuring virtually any physical product characteristic, with a water uptake apparatus to measure the swelling force and liquid uptake of a tablet containing a disintegrant. To mimic the tablet disintegrate in the patient’s mouth without plenty of water, the tablet were evaluated for their behavior in a limited water-providing environment.Hydrochlorothiazide was chosen as a model drug because it has poor solubility in water and its dissolution is largely dependent on the disintegration of tablets. Dicalcium phosphate dehydrate was used as an insoluble excipient and all tablets were prepared by direct compression. The disintegration and dissolution test were conducted in pH 1.2 HCl and pH 6.8 phosphate buffers according to USP XXX edition. Besides, simultaneously measuring the swelling force and water uptake of the tablet containing disinetgrants with a texture analyzer were studied to understand concentration effect and efficient for disintegrants, individually. The results show the efficiency of various disintegrants and the effect of pH was reduced as the 8% Ac-Di-Sol and 8% Primojel concentration was increased. Unlike Ac-Di-Sol and Primojel, polyplasdone XL was unaffected by pH changes. The efficiency of a disintegrant in a tablet does not proportionally increase with its concentration in the tablet because the liquid penetration inside the tablets was obstructed. Then, the swelling force generation rate was slow, which made the disintegrant less efficient. Anywhere, water-providing is a very important factor for the generation of swelling force and it usually becomes the decisive factor for the generation for swelling force at high concentrations.In conclusion, the standard compendia test may have limitations in discriminating between disintegration efficiency and mechanism, so this study combined texture analyzer and a water uptake apparatus to analyze superdisintegrants efficiency. |
