Carlson J A, Mann H J, Canafax D M
Am J Hosp Pharm. 1983 Aug;40(8):1334-6.
The effect of pH on the in vitro disintegration, dissolution, and solubility of ketoconazole tablets was studied. One 200-mg ketoconazole tablet was added to each of five different buffer solutions having pH values of 2 to 6;900 ml of each solution containing the ketoconazole was placed in a stationary basket dissolution device and stirred at 500 rpm at 37 degrees C for 60 minutes. Single 1-ml samples of each solution were obtained at 1,3, and 5 minutes after addition of the drug, and then every 5 minutes for the duration of the sampling period. This same procedure was repeated using two 200-mg tablets in the buffer solution at pH 3. The effect of pH on ketoconazole solubility was studied by gradually increasing the pH of a ketoconazole solution at pH 3 to pH 10. Samples of this solution were analyzed periodically after allowing a short period for equilibration of pH. All samples were assayed spectrophotometrically against blanks, and concentrations were determined by comparison with a standard curve. Disintegration of ketoconazole tablets occurred within 5 minutes in each buffer solution and was unaffected by pH. At pH 2 and 3, dissolution of ketoconazole was greater than 85% complete after five minutes, and all ketoconazole had dissolved after 30 minutes. As pH increased, the rate and extent of dissolution slowed; only 10% of ketoconazole was dissolved after 60 minutes at pH 6. Ketoconazole precipitated rapidly from solution as the pH of the dissolution medium exceeded 5.5. There was no difference in the rate or extent of dissolution of ketoconazole for the two doses studied at pH 3. In the buffer solutions tested, dissolution but not disintegration of ketoconazole tablets is pH-dependent. Dissolution characteristics of 200- and 400-mg doses of ketoconazole are similar at pH 3.
研究了pH值对酮康唑片体外崩解、溶出和溶解度的影响。将1片200毫克的酮康唑片分别加入到5种pH值为2至6的不同缓冲溶液中；将900毫升含有酮康唑的每种溶液置于固定篮式溶出装置中，在37℃下以500转/分钟搅拌60分钟。在加入药物后1、3和5分钟时，从每种溶液中取1毫升单一样品，然后在采样期内每隔5分钟取样一次。在pH值为3的缓冲溶液中使用2片200毫克的片剂重复相同的程序。通过将pH值为3的酮康唑溶液的pH值逐渐提高到10来研究pH值对酮康唑溶解度的影响。在允许pH值短暂平衡后，定期分析该溶液的样品。所有样品均与空白对照进行分光光度测定，并通过与标准曲线比较来确定浓度。酮康唑片在每种缓冲溶液中5分钟内发生崩解，且不受pH值影响。在pH值为2和3时，5分钟后酮康唑的溶出度超过85%，30分钟后所有酮康唑均已溶解。随着pH值升高，溶出速率和程度减慢；在pH值为6时，60分钟后只有10%的酮康唑溶解。当溶出介质的pH值超过5.5时，酮康唑迅速从溶液中沉淀出来。在pH值为3时，所研究的两种剂量的酮康唑的溶出速率或程度没有差异。在所测试的缓冲溶液中，酮康唑片的溶出而非崩解依赖于pH值。在pH值为3时，200毫克和400毫克剂量的酮康唑的溶出特性相似。
