The reciprocating cylinder was proposed by Beckett and coworkers41. and its incorporation into the USP followed in1991. The idea to generate a new test method came from a presentation at the International Pharmaceutical Federation (FIP) Conference in 1980 (U.S. Pharmacopoeial Convention).
USP Apparatus III (Reciprocating Cylinder) :-
The reciprocating cylinder was proposed by Beckett and coworkers41. and its incorporation into the USP followed in1991. The idea to generate a new test method came from a presentation at the International Pharmaceutical Federation (FIP) Conference in 1980 (U.S. Pharmacopoeial Convention).
In this presentation, problems with the dissolution results from USP Apparatuses I and II, which may be affected physical factors like shaft wobble, location, centering, deformation of the baskets and paddles, presence of the bubbles in the dissolution medium, etc. were enumerated. It was agreed at the conference that major problems could arise in the acceptance of pharmaceutical products in international trade due to the resultant variations in the dissolution data43.
A team of scientists working under Beckett’s direction in London, UK, subsequently developed the reciprocating cylinder, which is often referred to as the ‘‘Bio-Dis.’’ Although primarily designed for the release testing of extended-release products, USP apparatus 3 may be additionally be used for the dissolution testing of IR products of poorly soluble drugs44. In terms of design, the apparatus is essentially a modification of the USP/NF disintegration tester.
Figure: USP apparatus III
Principle and Design The development of USP Apparatus 3 was based on the recognition of the need to establish IVIVC, since the dissolution results obtained with USP Apparatuses I and II may be significantly affected by the mechanical factors mentioned in the preceding section. The design of the USP Apparatus III, based on the disintegration tester, additionally incorporates the hydrodynamic features from the rotating bottle method and provides capability agitation and media composition changes during a run as well as full automation of the procedure. Sanghvi et al.15 have made efforts to compare the results obtained with USP Apparatus III and USP
Apparatus I and II. Apparatus III can be especially useful in cases where one or more pH/buffer changes are required in the dissolution testing procedure, for example, enteric-coated/sustained release dosage forms, and also offers the advantages of mimicking the changes
in physiochemical conditions and extraordinarily strong mechanical forces experienced by the drug products in the mouth or at certain locations in the GI tract, such as the pylorus and the ileocecal valve. Apparatus III is currently commercially available with seven columns
of six rows, each row consisting of a set of cylindrical, flat bottomed glass outer vessels, a set of reciprob).
The screens are made of suitable materials designed to fit the top and bottom of the reciprocating cylinders. Operation involves the agitation, in dips per minute (dpm), of the inner tube within the outer tube. On the upstroke, the bottom tube in the inner tubes moves upward to contact the product and on the down stroke the product leaves the mesh and floats freely within the inner tube. Thus, the mechanics subject the product being tested to a moving medium. The USP Apparatus III is considered as the first line apparatus in product development of controlled-release preparations, because of its usefulness and convenience in exposing products to mechanical as well as a variety of physicochemical conditions which may influence the release of products in the GI tract13. The particular advantage of this apparatus is the technically easy and problem free use of test solutions with different pH values for each time interval. It also avoids cone formation for disintegrating (immediate release) products, which can be encountered with the USP apparatus II.
Ease of sampling, automation, and pH change during the test run, make it the method of choice in comparison to the rotating bottle apparatus, although both can lead to good correlations for extended-release formulations16. An additional advantage of apparatus III includes the feasibility of drug-release testing of chewable tablets. Chewable tablets for human use do not contain disintegrants, so they need to undergo physiological grinding (i.e., chewing) prior to dissolution. However, requirements concerning their biopharmaceutical quality are similar or identical to those for conventional immediate-release tablets. The use of compendia devices such as either stirred systems like the basket and the paddle apparatus or the flow-through cell apparatus were found not to provide suitable results for proper product cating inner cylinders and stainless steel fittings and characterization of chewable tablets. Pre-treatment by trituration to simulate mastication is not desirable because of the lack of standardization for this manual procedure. Furthermore, for safety reasons, it must be established that even when the unchewed tablets are swallowed, it would still release the active ingredient. The action produced by the reciprocating cylinder carries the chewable tablet being tested through a moving medium. The hydrodynamic forces in this apparatus were found to be stronger in comparison to Apparatus I and II3. The results showed that 5dpm (dips per min) in apparatus III is equivalent to 50 rpm in Apparatus II. Hence, higher dip rates are creating forces that may not be achieved by the use of the paddle instrument but which are highly desired to mimic human masticator forces.
Further experiments were performed to evaluate the suitability of the reciprocating cylinder apparatus to discriminate dissolution properties of different Pharmaceuticals including chewable tablets containing calcium carbonate18. The oscillatory movement of USP Apparatus III operated at 20dpm exhibited a high mechanical stress on the formulations. The results19 were discussed at the Royal British Pharmaceutical Society (RBPS)/FIP Congress in September 1999 and later included as a recommendation in the FIP/ AAPS guidelines20. The use of USP Apparatus III to characterize the drug release behavior of chewable tablets represents the state of the art, but there are also some concerns about the carry over and the effect of surface tension retarding complete drainage of the test fluid during the ‘‘hold’’ period between rows21.