Dissolution testing tablet

Sample preparation is critical for dissolution testing. Tablets or capsules may be placed in a sinker when using USP Apparatus 2 (paddle method). If USP Apparatus 1 (basket method) is used, then the baskets should be dry when samples are placed in them. 

Figure 4.50. Cumulative dissolution results. Two experimental tablet formulations were tested against each other in a dissolution test in which tablets are immersed in a stirred aqueous medium (number of tablets, constructional details and operation of apparatus, and amount of medium are givens). Eighty or more percent of the drug in either formulation is set free within 10 minutes. The slow terminal release displayed by formulation B could point towards an unwanted drug/excipient interaction. The vertical bars indicate ymean - with Sy 3%. A simple linear/exponential model was used to approximate the data for the strength 2 formulation. Strengths I and 3 are not depicted but look very similar.

G. Levy, J. R. Leonards, and J. A. Procknal, Development of in vitro dissolution tests which correlate quantitatively with dissolution rate-limited drug absorption in man, J. Pharm. Sci., 54, 1719-1722 (1966). K. A. Javaid and D. E. Cadwallader, Dissolution of aspirin from tablets containing various buffering agents, J. Pharm. Sci., 61, 1370-1373 (1972). 

M Aikman, L Augsburger, I Berry et al. Collaborative development of two-tiered dissolution testing for gelatin capsules and gelatin-coated tablets using enzyme-containing media. Pharmacop Forum 24(5) 7045-7050, 1998. 

FW Goodhart, RH McCoy, FC Ninger. New in vitro disintegration and dissolution test method for tablets and capsules. J Pharm Sci 62 304-310, 1973. 

Extensions of BCS beyond the oral IR area has also been suggested, for example to apply BCS in the extended-release area. However, this will provide a major challenge since the release from different formulations will interact in different ways with in vitro test conditions and the physiological milieu in the gastrointestinal tract. For example, the plasma concentration-time profile differed for two felodipine ER tablets for which very similar in vitro profiles had been obtained, despite the fact that both tablets were of the hydrophilic matrix type based on cellulose derivates [70], This misleading result in vitro was due to interactions between the gel strength of the matrix and components in the dissolution test medium of no in vivo relevance. The situation for ER formulations would be further complicated by the need to predict potential food effects on the drug release in vivo. 

Most manufacturers of dissolution testing devices offer semi-automated systems that can perform sampling, filtration, and UV reading or data collection. These systems automate only a single test at a time. Fully automated systems typically automate entire processes including media preparation, media dispensing, tablet or capsule drop, sample removal, filtration, sample collection or analysis (via direct connection to spectrophotometers or HPLCs), and wash cycles. A fully automated system allows automatic performance of a series of tests to fully utilize unused night and weekend instrument availability. 

It should be remembered that in 1970, when drug-release/dissolution tests first became official through the leadership of USP and NF, marketed tablets or capsules in general simply did not have a defined dissolution character. They were not formulated to achieve a particular dissolution performance, nor were they subjected to quality control by means of dissolution testing. Moreover, the U.S. Food and Drug Administration (FDA) was not prepared to enforce dissolution requirements or to even to judge their value. 

Over the years, dissolution testing has expanded beyond ordinary tablets and capsules—first to extended-release and delayed-release (enteric-coated) articles, then to transder-mals, multivitamin and minerals products, and to Class Monographs for non-prescription drug combinations. (Note at the time, sustained-release products were being tested, unofficially, in the NF Rotating Bottle apparatus). 

Figure 6 Different cell types for dissolution testing using the flow-through system. Type (a) tablet cell (12 mm), (b) tablet cell (22.6 mm), (c) cell for powders and granulates, (d) cell for implants, (e) cell for suppositories and soft gelatin capsules, (f) cell for ointments and creams.

Kraemer J. Chewable Tablets and Chewing Gums. Workshop on Dissolution Testing of Special Dosage Forms, Frankfurt, March 05, 2001 (oral presentation). 

USP 27 (2004) contains 185 capsule monographs representing 121 monographs with dissolution test and 15 other monographs with a drug-release test. Out of 527 tablet monographs, 346 contain a dissolution test while 21 cited a drug-release test (14). 

Implementation of dissolution testing by BP was in a tiered program similar to that employed at the time by USP. For the first category, products would conform to 75% release in 45 min. Where the drug had a narrow therapeutic index and should not release too rapidly, was known to exhibit a brief plasma half-life, or have site-specific absorption, additional testing to satisfy the need for greater control would be considered. Dissolution tests were included in 1980 for 14 tablet and four capsule monographs (15,16). 

A dissolution test was first described in the JP in 1981 (18). General rules for capsules and tablets stated that the requirements of the disintegration test must be met unless otherwise specified. Several specific capsule and tablet monographs included new dissolution tests. 

In the intervening years, the increase in specifications for oral dosage forms dissolution has been less dramatic. The 14th edition of the Japanese Pharmacopoeia (2002) has included additional dissolution tests for tablets and capsules. Out of a total of 61 tablet monographs, dissolution tests are included in 32. From four capsule monographs, one dissolution test is given (19). 

British Pharmacopoeial Commission. Dissolution test for tablets and capsules. In British Pharmacopoeia 1980. London Her Majesty s Stationary Office, 1980 A114. 

Recently, Yoshikawa et al. [70] reported a new in vitro dissolution test, called the rotating beads method, for drugs formulated in pressure-controlled colon delivery capsules. This dissolution method was applied to acetominophen sustained-release tablets and two other drugs having low solubility in the colon, tegafur and 5-ASA. There was good correlation between the in vitro dissolution rates and the in vivo absorption rates. 

M. Blanco, M. Alcala, J.M. Gonzalez and E. Torras, A process analytical technology approach based on near infrared spectroscopy tablet hardness, content uniformity, and dissolution test measurements of intact tablets, J. Pharm. Sci, 95, 2137-2144 (2006). 

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