Robotic dissolution

Aloba, O. T, Bergman, D. E., Miller, R., and Daly, R. E. Enhanced robotic dissolution system with concurrent off-line analysis. J. Pharm. Biomed. Ana 11 (10) 861—869, 1993. 

Functions to validate on automated dissolution systems may include bath operation, balance operation, media dispensing operations, media removal, sampling operations, media replacement, thermistor operation, robot operation, sample timing, sequence, and dilution. 

IV. HPLC IN AUTOMATED AND ROBOT-ASSISTED DISSOLUTION TESTING... 

A validated robotic system for dissolution assay of an immediate-release/ 186... 

Both microwave closed-vessel dissolution and laboratory robotics are relatively new to the analytical laboratory. However, it is this marriage of new methods which provides useful combinations of flexible laboratory automation to meet a variety of individualized needs. Because of the large number of biological samples which are prepared for analysis each day, it is reasonable to assume that this type of innovative automation wiU be of great benefit. It should be evaluated for its ability to improve the preparation technology for trace element analysis of biological materials. 

A VALIDATED ROBOTIC SYSTEM EOR DISSOLUTION ASSAY OE AN IMMEDIATE-RELEASE/SUSTAINED-RELEASE TABLET... 

A Zymate XP dissolution robot equipped with a balance and a six-spindle dissolution tester with remote interface was used. This equipment is shown in Fig. 6.10. 

The dissolution method for the immediate-release/sustained-release tablet requires the following parameters USP paddle method, 900 ml of water, SO rpm paddle speed, 37°C, and samphng points at 20 minutes, 40 minutes, 1, 2, 4, 6, 8 and 10 hours. Robotically, ahquots (8 ml) were removed, filtered through a 10 jm polyethylene filter and transferred to the storage rack. The volume (8 ml) was replaced with heated media. The samples were assayed hy HPLC using the external standard method. 

Fig. 6.10 Dissolution bench layout showing orientation of robot [30]. Reproduced with permission of Zymark Corporation.

Buegelsdijk et al. described a fully automated system for preparation of dissolved Pu metal samples using the Zymate II (Zymark Corporation) laboratory robot.67 The sample preparation steps included bar-code label reading, weighing the sample, and transfer to the dissolution vessel. 

The various applications of the analysis of tablets for dissolution testing, content uniformity, stability-indicating assays, and routine quality control assays have all been targets of automation using a robot system. 

The amino acid module performs the dissolution, activation, and delivery of amino adds to the synthesis cabinet. This is accomplished via a robotic arm with a probe attachment. Liquids can be dispensed or withdrawn from amino acid vials through the probe. In addition, nitrogen can be bubbled to aid in the dissolution of the amino acid. After each amino acid coupling the probe is thoroughly washed, both internally and externally, to eliminate cross contamination. The amino acid module can hold up to 72 anoino acids in three 24-position racks. A rack can be assigned to each colunm or all 72 can be used for single column synthesis. 

Additional modules not always required in a robotic station include a cappinguncapping module, used to remove and replace screw caps a bar-code reader, which is usually a laser bar-code scanner combined with a turntable assembly capable of reading a label positioned anywhere around the circumference of a vial and an ultrasonic hath, which is required for sonic mixing or cleaning, but also, occasionally, to facilitate dissolution or leaching. 

Three approaches to the automation process can be distinguished, taking into account the criterion of the flexibility of the automation device [2], The first, denoted as flexible, is characterized by the possibility of adaptation of the instruments to new and varying demands required from the laboratory examples of these instruments are robots. The second approach, denoted as semiflexible, involves some restrictions for the tasks executed by the instrument the tasks are controlled by a computer program and its menu. As examples, autosamplers or robots of limited moves can be given. In the third approach, the instruments can execute one or two tasks, without feasibility of new requirements as examples, supercritical fluid extractors or equipment for dissolution of samples can be given. 

A short discussion of new high-throughput applications of methodologies for solid dosage forms is presented in Chapter 6. Examples include fiber-optic dissolution technology, flow injection analysis, NIR analysis, and robotics. These techniques provide data with less analyst involvement and allow a more thorough batch quality assessment. 

The second focus of this chapter will be on high-throughput techniques for the assessment of product quality. These techniques—NIR analysis, fiberoptic dissolution, robotics, and flow injection analysis (FIA)—promise to allow the analyst more time for problem solving, invention, and interaction with the analytical department s multiple customers. 

Almost all aspects of manual analyses have been automated, ranging from sample handling to measurement with automated calculation and report generation. -96 yhgjjg automated analyses have been applied to many types of tests, including assay, content uniformity, dissolution, and moisture, and are routinely used for product release and stability testing. Some companies have constructed complete robotic laboratories in a centralized or decentralized manner to generate tens of thousands of assay results per year. 

It is the first stage of laboratory analytical methodologies which poses the greatest problems for automation (see Chapter 2). Operations such as weighing, dissolution, grinding and centrifugation are difficult to incorporate on-line in automatic analysers (whether batch or continuous). It is therefore here that robotic systems cover a field inaccessible to the remainder of automatic methodologies. 

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