Dosage automation

When performing dissolution testing, there are many ways that the test may generate erroneous results. The testing equipment and its environment, handling of the sample, formulation, in situ reactions, automation and analytical techniques can all be the cause of errors and variability. The physical dissolution of the dosage form should be unencumbered at all times. Certain aspects of the equipment calibration process may show these errors as well as close visual observation of the test. The essentials of the test are accuracy of results and robustness of the method. Aberrant and unexpected results do occur, however, and the analyst should be well trained to examine all aspects of the dissolution test and observe the equipment in operation. 

For further information on sampling and automation of sampling, including a discussion of apparatus suitability test acceptance criteria for IR or MR dosage forms, please refer to Chapters 2, 3, and 13. 

P. R. Rege, V. D. Vilivalam, and C. C. Collins. Development in release testing of topical dosage forms Use of the Enhancer Cell(TM) with automated sampling. J. Pharm. Biomed. Anal. 17 1225-1233 (1998). 

As stated earlier, the SP trend in the pharmaceutical analysis of solid dosage forms is dominated by manual batch techniques such as grinding, sonication, dilution in volumetric flask and filtration. The unique SP requirements for solid dosages in grinding and handling large volumetries are particularly difficult to automate. 

When attempting to convert a manual method into an automated method, there are certain elements, such as tablet size and solvent selection, which will have an impact on the ease of the conversion from manual to automated. For instance, some of the elements of an assay method that would make it easier to automate would be that the dosage form fits into a test tube the extraction uses neutral media or acid not more concentrated than 0.1 M makes use of nonvolatile, low-toxicity solvents does not use surfactants and uses premixed, room-temperature solvents. Some of the elements of a dissolution method that would make it easier to automate would be that the dosage form fits in the sample carousel, does not use media more concentrated than 0.1 M acid, does not use isopropanol or surfactant in large quantities, uses magnetic sinkers or no sinkers at all, and uses no or minimal reagent addition volumes for pH control. 

Figures 23.3 through 23.5 illustrate the stepwise process low typically utilized in wet and dry granulation techniques for the manufacture of tablet dosage forms. For capsules, the process tends to be simpler with utilization of Lrst three steps from dry granulation followed by encapsulation in appropriate-size capsule shells. Depending on the batch size, a manual LHer (e.g., Bonapace), semiautomatic encapsulator (e.g., Capsugel Ultra 8), or automated encapsulator (Zanasi, Macofar, etc.) could be utilized for manufacturing.

Sephadex G-25 buffered at alkaline pH s has been found to possess excellent resolving power in some cases (144, 145, 146). A column liquid chromatographic method for determining TC in various dosage forms was automated. Each chromatogram consisted of a continuous flow separation of components followed by a spectral determination of the column eluate at a rate of 12 samples per hour (147). Gel chromatography has also been applied to the analysis of TC antibiotics using a Bio-Gel P-2 column with 0.1M acetic acid as an eluent (148). 

Dissolution testing for solid dosage forms generates numerous samples that can be automated using the Zymate Dissolution Testing System. -This system automates the vessel cleaning, sample addition, media addi-... 

E. Lamparter and Ch. Lunkenheimer, The automation of dissolution testing of solid dosage forms, J. Pharm. Biomed. Anal., 10 127 (1992). 

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