【正文】 be investigated to identifythe lowest concentration neededto achieve sink conditions. Typically,the surfactant concentration is above its critical micellar concentration(CMC). Table 1 shows a list of some of the surfactants used indissolution media. Approximate CMC values are provided with referenceswhenavailable. The list is not prehensive and is not intended to exclude surfactantsthat are not listed. Other substances, such ashydroxypropyl b cyclodextrin,have been used as dissolution media additives to enhance dissolution of poorlysoluble . Food and Drug Administration (FDA) maintains adatabase of dissolution methods, including information on dissolution mediathat have been used (1). Typically, the amount of surfactant added issufficient to achieve sink conditions in the desired volume of dissolutionmedium.有時候水溶性介質中（酸性水溶液或緩沖溶液）可能添加一定比例的表面活性劑（如十二烷基硫酸鈉（SDS），聚山梨醇酯，或十二烷基二甲基氧化胺）以提高藥物的溶解度。在使用HPLC方法進行分析時，不同來源的聚山梨酯（吐溫）80會影響它的適用性。Investigations of the stability of thedrug substance should be carried out, when needed, in the selected dissolutionmedium with excipients present, at 37176。溶解介質的組成和體積應根據(jù)溶解度的試驗結果進行調整。同時，緩沖液的離子強度或體積摩爾濃度是可以控制的。根據(jù)具體情況進行解決，可能的解決方案包括：酸性介質中添加表面活性劑或者調整質量標準）During selection of the dissolutionmedium, care should be taken to ensure that the drug substance is suitablystable throughout the analysis. In some cases, antioxidants such as ascorbicacid may be used in the dissolution medium to stabilize the drug. There areoccasions where such actions are not sufficient. For pounds that rapidlydegrade to form a stable degradant, monitoring the degradant alone or inbination with a drug substance may be more suitable than analyzing only thedrug substance. In situ spectroscopic techniques tend to be less affected bydegradation when pared with HPLC analysis (including UHPLC and other liquidchromatographic approaches).在選擇溶解介質時，應注意采取措施確保原料藥在整個分析過程中的穩(wěn)定性。在某些情況下，根據(jù)藥物的濃度和漏槽條件，可使用較大的溶出杯，體積可以增加至2～4升（這種方法必須有充分的理由）。當儀器1或儀器2不適用時，可以使用其他官方儀器。 for example, a basket mesh size other than the typical40mesh basket (., 10, 20, or 80mesh) may be used when the need isclearly documented by supporting data. Care must be taken that baskets areuniform and meet the dimensional requirements specified in 711.對藥典儀器配件也可以進行一些調整；例如，除了藥典儀器40目以外的其他規(guī)格的溶出籃（例如：10，20或者80目），通過充足的數(shù)據(jù)進行詳細的闡明后也可以使用。如果在10分鐘 12個樣本的相對標準偏差（RSD）不得過20%或者后續(xù)取樣點的RSD值大于10%。根據(jù)不同的問題，通常的調節(jié)方法包括下列任何一個因素的改變：儀器，轉速，脫氣程度，沉降籃類型，或者溶出介質的組成。在711部分附錄中描述了脫氣方法。如果檢測結果表明脫氣對溶出結果沒有影響，該試驗就可以作為不需要進行脫氣的理由進行說明。有幾種可用的商業(yè)類型的沉降籃。評估沉降籃的不同類型，同時要認識到沉降籃能夠顯著影響溶出曲線。Media containing surfactants usuallyare not deaerated because the process results in excessive foaming, and usuallythe effect of dissolved air on the dissolution process is mitigated by thereduced surface tension of the medium. Sometimes, deaerating the medium beforeadding surfactants can be effective.含有表面活性劑的溶出介質由于脫氣過程會產生過多氣泡通常不容易脫氣，通常采用減少溶出介質中的表面張力，來減輕溶解的空氣對溶解過程產生的影響，有時，在加入表面活性劑之前對溶出介質進行脫氣是有效的。劑量單位上的氣泡可能會增加浮力，導致溶解速率增加，或者也有可能會減少可接觸的表面積導致溶出率下降。試驗過程的觀察往往有助于查找產生變異的原因或者溶出度測定方法本身是否會產生變異性。結果的高變異難以確定處方變化的趨勢和處方變化對溶出度結果的影響。半固態(tài)劑型，常用的儀器包括立式擴散池，浸入細胞，流通單元儀器適用局部制劑（see Semisolid DrugProducts—Performance Tests 1724）。一般來說，首選藥典儀器。 justification for this approach is expected. Inpractice, the volume of the dissolution medium is usuallymaintained within the pendial rangegiven above. Alternatively, it may be preferable to switch to other pendialapparatus, such as a reciprocating cylinder (Apparatus 3), reciprocating holder(Apparatus 7), or flowthrough cell (Apparatus 4).Certain applications may require lowvolumes of dissolution media (., 100–200 mL) when the use of a paddle orbasket is preferred. In these cases, an alternative, nonpendial apparatus(., smallvolume apparatus) may be used.對于藥典儀器1（籃法）和儀器2（槳法），溶出介質的體積可以從500到1000毫升不同。An acid stage is part of the testing ofdelayedrelease products by Method A or Method B in 711. For drugs with acid solubility less than 10% of the labelclaim or drugs that degrade in acid the usefulness of the acid stage indetecting a coating failure is promised. This would be handled on acasebycase basis. Possible resolutions include the addition of surfactant tothe acid stage, or adjustment of the specifications.對于腸溶制劑，酸中釋放度是溶出度的一部分（711方法A或者方法B）。這些溶出介質可以含有生理表面活性成分，如牛黃膽酸。當滿足漏槽條件后，溶出度結果能夠更好的反映藥物制劑的質量。不推薦使用純化水作為溶出介質的原因：水的質量變化取決于它的來源，而水的pH值不像緩沖溶液能夠嚴格控制；此外，若藥物和輔料的溶出對pH值敏感時需要考慮使用緩沖液。It is important to control thegrade and purity of surfactants because use of different grades could affectthe solubility of the drug. For example, SDS is available in both a technicalgrade and a highpurity grade. Obtaining polysorbate 80 from different sourcescan affect its suitability when performing highperformance liquidchromatography (HPLC) analysis.由于使用不同級別的表面活性劑會影響藥物的溶解度，因此要控制表面活性劑的級別和純度。對于一些藥物，與藥物不相容的特定緩沖液或鹽可能會影響緩沖劑的選擇。). The pHof the clear supernatant should be checked to determine whether the pH changesduring the solubility test. Alternative approaches for solubility determinationmay also be used.在選擇合適溶出介質的過程中，需要確定原料藥的物理化學特性。通過試驗比較過濾和未過濾的標準溶液和樣品溶液的含量差別，驗證該過濾器是合適的。此外，過濾后的溶出物不干擾分析檢測也是非常重要的，這可以通過過濾后的溶出介質過濾與未過濾的溶出介質進行比較，評估濾膜是否干擾分析測定。如果原料藥的粒度很?。ɡ?，微分化顆粒或納米顆粒），找到一個合適的過濾器過濾這些小顆粒至今仍具有挑戰(zhàn)性。如果不把未溶解的藥物和輔料從樣品溶液中除去，那么未溶解的藥物顆粒將會繼續(xù)溶解使試驗結果出現(xiàn)偏差，因此，如果取樣管中沒有過濾器，應立即對溶出度樣品進行過濾。同時它還涉及對普通制劑和緩釋制劑所生成的數(shù)據(jù)和接受標準進行說明。關于設備和方法的修改部分在USP通則中給出了合理的說明。在選擇濾膜時有必要重點考慮濾膜的材料、型號和孔徑大小。不同的過濾材料表現(xiàn)出與藥物結合的不同特性。使用大孔徑濾膜過濾小體積溶液，能夠導致樣品溶液損失量過大而收集不到所用樣品量；使用小孔徑濾膜過濾，需要更高的壓力和較長的時間，并且溶液迅速堵塞濾膜。對于標準溶液，比較過濾溶液（棄去的適當體積后）和未過濾溶液的含量測定結果；對于樣品溶液，比較過濾（棄去適當體積后）、離心、未過濾樣品溶液的含量測定結果。為了消除溶出介質中藥物和緩沖液之間離子的潛在影響，使用鹽酸和氫氧化鈉的混合物對溶解度進行研究，這是一種典型的緩沖溶液。選擇用于溶解度研究的表面活性劑時應涵蓋所有常用種類的表面活性劑，比如陰離子、非離子型和陽離子，當已經(jīng)確定一個合適的表面活性劑時，應對表面活性劑的不同濃度進行研究，以確定達到漏槽條件所需的最低濃度。There may be effects of counterions orpH on the solubility or solution stability of the surfactant solutions. Forexample, a precipitate forms when the potassium salt for the phosphate bufferis used at a concentration of M in bination with SDS. This can beavoided by using the sodium phosphate salt when preparing media with SDS.反離子或pH值