Abstract
Background: Dissolution testing of the 25 mg dapivirine (DPV) vaginal ring has historically relied on a non-compendial shaking incubator method. Typically, individual rings in a sealed glass flask containing a defined volume of release medium are placed in a temperature-controlled shaking incubator. Flasks are regularly and periodically sampled (usually with medium replacement) over weeks or months. Here, we compare dissolution data for 25 mg DPV rings using the United States Pharmacopeia (USP) rotating paddle method (Apparatus 2) and the shaking incubator method.
Methods: 25 mg DPV, matrix-type, silicone elastomer vaginal rings were supplied by QPharma (Malmö, Sweden). Rotating paddle dissolution testing in both isopropanol+water (1:1 v/v; 300 mL) and simulated vaginal fluid (SVF) modified with 0.2% w/v Tween 80 (300 mL) was performed using a ERWEKA DT 126 Light Dissolution Tester (50 rpm, 37°C). Shaking incubator dissolution testing of the rings was also performed, as described in the literature (100/200 mL, 37°C, 25 mm orbital diameter). DPV concentrations were quantified by HPLC.
Results: Dissolution data obtained using the rotating paddle method were generally similar to those obtained with the shaking incubator method. Both methods showed a burst effect followed by gradually decreasing daily release rates, in compliance with t1⁄2 kinetics. A major limitation of the rotating paddle method was the significant loss of dissolution medium volume due to evaporation from the open glass vessels. On average, 6 and 26 mL per day was lost from the SVF+Tween and isopropanol+water volumes, respectively. Moreover, the volume losses were dependent upon the position of the glass vessels within the flow-through water bath of the dissolution apparatus and the environmental conditions.
Conclusions: The non-compendial shaking incubator method for dissolution testing of 25 mg dapivirine vaginal rings offers increased practicality and reproducibility compared with the USP rotating paddle method.
Methods: 25 mg DPV, matrix-type, silicone elastomer vaginal rings were supplied by QPharma (Malmö, Sweden). Rotating paddle dissolution testing in both isopropanol+water (1:1 v/v; 300 mL) and simulated vaginal fluid (SVF) modified with 0.2% w/v Tween 80 (300 mL) was performed using a ERWEKA DT 126 Light Dissolution Tester (50 rpm, 37°C). Shaking incubator dissolution testing of the rings was also performed, as described in the literature (100/200 mL, 37°C, 25 mm orbital diameter). DPV concentrations were quantified by HPLC.
Results: Dissolution data obtained using the rotating paddle method were generally similar to those obtained with the shaking incubator method. Both methods showed a burst effect followed by gradually decreasing daily release rates, in compliance with t1⁄2 kinetics. A major limitation of the rotating paddle method was the significant loss of dissolution medium volume due to evaporation from the open glass vessels. On average, 6 and 26 mL per day was lost from the SVF+Tween and isopropanol+water volumes, respectively. Moreover, the volume losses were dependent upon the position of the glass vessels within the flow-through water bath of the dissolution apparatus and the environmental conditions.
Conclusions: The non-compendial shaking incubator method for dissolution testing of 25 mg dapivirine vaginal rings offers increased practicality and reproducibility compared with the USP rotating paddle method.
| Original language | English |
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| Number of pages | 1 |
| Publication status | Published - 25 Oct 2018 |
| Event | HIV Research for Prevention 2018 - Madrid Marriott Auditorium Hotel, Madrid, Spain Duration: 21 Oct 2018 → 25 Oct 2018 http://www.hivr4p.org |
Conference
| Conference | HIV Research for Prevention 2018 |
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| Abbreviated title | HIVR4P 2018 |
| Country/Territory | Spain |
| City | Madrid |
| Period | 21/10/2018 → 25/10/2018 |
| Internet address |