Haase Mark R, Khan Mansoor A, Bonilla Jeremiah
Texas Tech University Health Sciences, Center School of Pharmacy.
Int J Pharm Compd. 2003 Nov-Dec;7(6):485-9.
The short-term stability of two different concentrations of extemporaneously compounded tiagabine suspensions was studied. Six bottles each of 6-mg/mL and 2-mg/mL suspensions were compounded using commercially available 16-mg tiagabine tablets in a 1:1 mixture of Ora-Sweet and Ora-Plus. For each concentration, three bottles were stored in the dark in a stability chamber at 23 to 25 deg C, and three were stored in the dark in a refrigerator at 3 to 5 deg C, for 61 days. The stability of tiagabine in each of the concentrations and environmental conditions was determined after preparation and at 7, 14, 28, 42, and 61 days by means of a high-performance liquid chromatographic method, which involved a reverse-phase column, a gradient mobile phase containing acetonitrile and aqueous phosphoric acid at a flow rate of 2.75mL/minute. Detection was carried out by an ultravioldet spetrophotometer at 254 nm. The drug tiagabine, the internal standard (propylparaben) and degradant eluted at 8.4, 8.6, and 9.9 minutes, respectively. The high-performance liquid chromatographic validation involved limit of detection, limit of quantitation, accuracy and precision and interday and intraday variation. There was no appearance of degradation products in eiher concentration at any time. The suspensions stored at 23 to 25 deg C became slightly discolord after day 30 , turning slightly gray from blue. However, this change could not be attributed to tiagabine degradation. The refrigerated suspensions were found to be stable (retention of 90% potency) up to 40 days. The 6-mg/mL suspensions were stable up to the study period of 61 days; however, the 2-mg/mL suspension at 3 to 5 deg C showed a potency of 87.7% on day 61 of the study. Extemporaneously compounded liquid oral preparations of tiagabine 6mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet were stable for 61 days at 23 to 25 deg C and 3 to 5 deg C. The extemporaneously compounded liquid oral preparations of tiagabine 2mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet were stable for 61 days at 23 to 25 deg C and for 40 days at 3 to 5 deg C.
研究了两种不同浓度的临时配制的替加宾混悬液的短期稳定性。使用市售的16毫克替加宾片剂，以Ora-Sweet和Ora-Plus 1:1的混合物配制6毫克/毫升和2毫克/毫升的混悬液各6瓶。对于每种浓度，3瓶在23至25摄氏度的稳定性试验箱中避光保存，3瓶在3至5摄氏度的冰箱中避光保存，为期61天。在制备后以及第7、14、28、42和61天，通过高效液相色谱法测定每种浓度和环境条件下替加宾的稳定性，该方法使用反相柱、含有乙腈和磷酸水溶液的梯度流动相，流速为2.75毫升/分钟。通过紫外分光光度计在254纳米处进行检测。替加宾药物、内标（对羟基苯甲酸丙酯）和降解产物的洗脱时间分别为8.4分钟、8.6分钟和9.9分钟。高效液相色谱验证包括检测限、定量限、准确度和精密度以及日间和日内变化。在任何时候，两种浓度下均未出现降解产物。在23至25摄氏度下保存的混悬液在第30天后略有变色，从蓝色变为浅灰色。然而，这种变化不能归因于替加宾的降解。发现冷藏的混悬液在40天内稳定（效价保持在90%）。6毫克/毫升的混悬液在61天的研究期内均稳定；然而，在研究的第61天，3至5摄氏度下的2毫克/毫升混悬液的效价为87.7%。在Ora-Plus和Ora-Sweet 1:1的混合物中临时配制的6毫克/毫升替加宾液体口服制剂在23至25摄氏度和3至5摄氏度下稳定61天。在Ora-Plus和Ora-Sweet 1:1的混合物中临时配制的2毫克/毫升替加宾液体口服制剂在23至25摄氏度下稳定61天，在3至5摄氏度下稳定40天。
