Agilent Vacuum-Formed (VF) Molded Dissolution Vessels

1 Agilent Vacuum-Formed (VF) Molded Dissolution Vessels Technical Overview Introducing a Premium Dissolution Vessel for Optimal Reproducibility Dissolution is a technique used in the pharmaceutical industry to determine the rate at which pure active pharmaceutical ingredients enter into a solvent to yield a solution. The newly introduced VF Molded Vessels are vacuum formed around a set of Agilent mandrels, rather than through traditional hand-blown manufacturing, to maintain consistency and ensure exact speci cations. This process guarantees proper geometry and eliminates warps and aws, all with the intent to avoid possible interference from the Vessels being used.

2 The results should be indicative of the dosage form itself, not the equipment.. Allan Little, Director of Marketing, Dissolution As the transition to enhanced Mechanical Quali cation (MQ) continues to gain traction throughout the industry, these Vessels ll a void created by not performing the USP. Figure 1. An Agilent VF Molded Vessel. Performance Veri cation Test (PVT) using Prednisone tablets. The Vessels are available in standard and veri ed versions of TruAlign for the 708-DS Dissolution apparatus, as well as the legacy EaseAlign for the 7000/7010 apparatus and TruCenter for the legacy 7025 apparatus.

3 The veri ed versions include individual Certi cates of Conformance (COCs) a requirement for enhanced MQs. These Vessels provide users of Agilent Dissolution instrumentation a way to acquire premium accessories and continue to not just meet but exceed current regulatory requirements. What makes this process through a Certi cate of Conformance of the Dissolution media surrounding unique? (COC) or Certi cate of Analysis (COA) the paddle6. This study found that not was mandated in the FDA3 and ASTM4 only do Vessels vary between vendors, Dissolution Vessels are traditionally mechanical quali cation procedures.

4 But differences among Dissolution manufactured by hand-blowing and Vessels from the same source were also shaping standard stock glass tubing. Vessel inconsistency can also be a key observed6. In addition to differences in This can cause variability in height, source of variability, especially in the USP volume below the paddle, differences diameter, and speci c geometry of the PVT. In fact, vessel irregularities were were found in the distance between the inner vessel among vendors and even identi ed as the second highest potential paddle tip and vessel wall leading to: from the same vendor.

5 While hand- cause of variability in Prednisone blown Vessels produced today generally testing, with the rst being dissolved heterogeneous shear rates in the meet the speci cations in USP <711> gasses5. A key nding of this USP study hemispheric region of the Dissolution Dissolution1, the quality of the Vessels was that switching from one set of vessel. Given the differences in both the varies tremendously around the world. Vessels to another, similar set of Vessels paddle-vessel wall clearance and in the This variability can lead to signi cant leads to signi cant differences in both volume of Dissolution media surrounding differences in the hydrodynamics of the mean percent dissolved and standard the paddle, hydrodynamics in the Dissolution environment, which, in turn, is deviation, suggesting that the current hemispheric region of the vessel could be re ected in the Dissolution rates.

6 Geometric acceptance ranges may not be in uenced by variability of the dimensions appropriate5. of this critical region of the Dissolution Vacuum-Formed (VF) Molded Vessels vessel6.. are made using a different process than Vessel dimensions are critical in conventional hand-blown glass Vessels , Dissolution testing because they are Changes in the diameter between offering tighter control over vessel directly correlated with differences the Vessels are also important as dimensions that are critical to ensure in hydrodynamic mixing patterns and inconsistent diameters will result in a reproducible Dissolution test.

7 The the volume present below the shaft. differing angular momentum7.. Vessels are manufactured by forming Analysis of multiple vessel vendors the glass around a mandrel, which found high levels of variability between Of additional concern are aberrations maintains consistency and eliminates vessel suppliers resulting in as in the vessel which can occur as spurs, warps and other aws which can much as an 18% change in the volume fans, draws, depressions, and plains. occur with traditionally made Vessels . Though the manufacturing process is time consuming, Agilent invested in a Standard versus VF Molded Vessels Comparison proprietary set of mandrels to ensure the tightest speci cation possible to provide Standard far better control over the key parameters.

8 VF ( Molded ). Geometric error (mm). Why replace standard Vessels with VF Vessels ? A key objective when performing Dissolution testing is controlling external sources of energy and variability. The Dissolution test should be indicative of le ity ty y o . cit ici the dosage form, not the apparatus or ar Pr tri dr ul en rc lin accessories. At Agilent , we go to great Ci nc Cy Co lengths to eliminate or minimize every De nitions: source of variability. Circularity (Roundness) Pro le The measure of the sharpness of a A three-dimensional pro le tolerance that Vessel dimensions are one of the highest particle's edges and corners.

9 Describes the allowable variability in the contour of a surface. areas of risk and can create potential Cylindricity sources of variability in the suitability A three-dimensional geometric Concentricity of a Dissolution apparatus2. Because of tolerance that controls how much a A three-dimensional locational tolerance that feature can deviate from a perfect describes the location of opposing points in this risk, guidance for documentation cylinder. cylidrical features with respect to a datum of individually measured components reference.

10 Figure 1. Shape comparisons between standard Vessels and Agilent VF Molded Vessels . 2. These various deformations will also lead the tightest speci cations possible to Conclusion to increased variability versus a Molded eliminate the variability often seen with Molded Vessels provide a high level of vessel. Further discussion of these hand-blown Vessels . These Vessels have con dence in vessel geometry and better deformations are found in Peter Scott's tolerances that, for certain parameters, consistency in hydrodynamics within the article Geometric Irregularities Common are more than 10 times tighter than Dissolution vessel.