Tablet testing medium

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. 

Lejoyeaux, F., et al. 1989. Bioadhesive tablets Influence of the testing medium composition on... 

Figure 7.3 In vitro dissolution-time profiles of a poorly soluble compound, felodipine, for three different hydrophilic matrix extended release tablets CA-C) when three different surfactants CSLS, CTAB, Tween) were used in the dissolution test medium at levels providing sink conditions .

The ionic concentration in the test medium can affect both the drug solubility and the release mechanism for modified-release formulations. One example of the latter case is hydrophilic gel matrix tablets, a type of ER tablet that forms a gel layer in contact with the GI fluids. Solutes will affect the hydration of the gel matrix and, thereby, affect the drug release rate. 

It has been shown for such tablets that the correlation to in vivo data can be completely lost by use of inappropriate ionic compositions in the test medium (Abrahamsson et al. 1998a). For ER formulations with osmotically driven drug release, a decreased drug release rate approaching no release will occur for high ionic concentrations in the test medium, and misleading in vitro results maybe obtained if a relevant ionic composition is not used (Lindstedt et al. 1989). 

Figure 3 Effect of the pH of the dissolution medium on the release of mesalazine tablets tested in pH 6.5 (open symbols) and 7.0 (closed symbols) mixed phosphate buffers. The mesalazine core tablets were coated with Eudragit LlOO-55 and Eudragit SlOO combinations of 1 4 (squares), 1 5 (triangles), and 0 1 (circles) ratios (w/w) and tested in 0.1 N HCl for 120 min prior to the buffer stage. The dissolution test was performed using United States Pharmacopoeia method B for extended-release tablets. The vertical bars indicate standard errors of the means (n = 6). (Adapted from Ref. 35.)...

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.

In the disc method, the powder is compressed by a punch in a die to produce a compacted disc, or tablet. The disc, with one face exposed, is then rotated at a constant speed without wobble in the dissolution medium. For this purpose the disc may be placed in a holder, such as the Wood et al. [Ill] apparatus, or may be left in the die [112]. The dissolution rate, dmldt, is determined as in a batch method, while the wetted surface area is simply the area of the disc exposed to the dissolution medium. The powder x-ray diffraction patterns of the solid after compaction and of the residual solid after dissolution should be compared with that of the original powder to test for possible phase changes during compaction or dissolution. Such phase changes would include polymorphism, solvate formation, or crystallization of an amorphous solid [113],... 

In one case, the formulation barely released any drug under the pH 1.2 condition. This could be traced back to the disintegration behavior, as little or no disintegration was observed at the low pH. Subsequently, a full-change method was used to determine whether exposure to low pH would harm release at pH 6.8 (Fig. 3). As can be seen from the graph, release was almost as complete when tested after exposure to pH 1.2 for an hour as when the tablet was placed in a pH 6.8 medium from the outset. These results underscore the... 

Fully automated workstations can automatically fill vessels with dissolution medium, drop the tablets or capsules, collect multiple samples, and clean vessels. Zymark MultiDose Automated Dissolution Workstation (Zymark Corporation, Hopkinton, MA), Sotax AT70 Smart (Sotax Corporation, Horsham, PA), and AUTO DISS systems (Pharma Test GmbH, Hainburg, Germany) are several popular automated systems used within the pharmaceutical industry. 

In the pharmaceutical industry, it is important that aU products are properly tested and vahdated prior to release for sale. One of the most important tests is the determination of tablet dissolution rate. In this procedure tablets are immersed in a suitable medium to mimic the action of the stomach and the release of the active ingredients monitored over a period of time. Automation of these procedures is obviously important for various reasons including cost, accuracy of analysis and for validation of the results according to good laboratory practice. 

To test the foregoing dimensionless relationship, two powders (Avicel Pl 1101, a ductile, viscoelastic material, and Emcompress, a brittle material, blended with 0.5% magnesium steaiate) were compressed on the PressterTw, a single-station mechanical replicator of rotary tablet presses. In the first set of experiments, a 16-station Manesty Betapress (a research-scale press) was simulated at two speeds, 60 and 100 rpm. In the second set, a 36-station Fette P2090 (a medium-scale production press) was simulated at two speeds, 55.8 and 70 rpm. It should be noted that 100 rpm of the Beta-press corresponds to 55.8 rpm of the Fette 2090 in terms of the linear speed of the turret. Basic parameters for the two tablet presses arc presented in Table 3. 

The dissolution method for pentazocine hydrochloride tablets utilizes a UV determination of pentazocine in filtered test samples at 278 nm. The apparatus used is USP number two at 50 rpm with water as the dissolution medium. The solutions are measured in hydrochloric acid diluted with dissolution medium to give 0.01 N HC1 and quantitatively compared to a suitable standard (46). 

The apparatus suitability test described in USP General Chapter <711> Dissolution is equivalent to a performance qualification.5 The determination of suitability of a test assembly to perform dissolution testing must include conformance to the dimensions and tolerances of the apparatus. In addition, the critical test parameters that have to be monitored periodically include volume and temperature of the dissolution medium, rotation speed (Apparatuses 1 and 2), dip rate (Apparatus 3), and flow rate of medium (Apparatus 4). This test requires that the USP Calibrator Tablets (now known as Performance Verification Standard Tablets) be tested the dissolution results must be within the ranges stated in the certificate of the calibrator tablets. The performance verification standard tablets include USP Chlorpheniramine Maleate Extended-Release Tablets RS, USP Prednisone Tablets RS, and USP Salicylic Acid Tablets RS. 

This is the place to start, since most often, analytical chemists are trying to help solve someone else s problem. We need to define the solute and its matrix as well as the nature of the analytical problem. For example, in the world of pharmaceuticals, there are raw material identification and purity determinations, in-process testing, dosage-form determinations, content uniformity, dissolution testing, stability studies, bioavailability, pharmacokinetics, and drug metabolism, to name a few. Each of these analytical problems has its own specific requirements. The matrix can be a raw material, granulation, tablet, capsule, solution, lotion, cream, syrup, dissolution medium, blood serum, urine, or various body tissues and fluids. Similar definitions can be described for virtually any industrial area and problem set. These definitions will help select sample preparation, separation, and detection techniques. 

There are several variants to this apparatus, which is based on a sample holder that oscillates up and down in the medium vessel. The sample holder may take the form of a disk, cylinder, or a spring on the end of a stainless steel or acrylic rod, or it may simply be the rod alone. The sample is attached to the outside of the sample holder either by virtue of being self-adhesive (e.g., transdermal delivery system) or is glued in place using a suitable adhesive. This apparatus may be used for transdermal products, coated drug delivery systems, or other suitable products (e.g., osmotic pump devices). It is prescribed for the drug-release testing of Psuedoephedrine hydrochloride extended-release tablets USP where the tablets are enclosed in a 5x5 cm of nylon, which is then attached to the rod. 

The USP directs that the thermometer should be removed before the test and that the temperature should be checked periodically. The dissolution fluids should be maintained at 37 0.5°C as even slight temperature variations may have a significant effect on tablet dissolution. It is essential, therefore, to prevent evaporation of the medium both to reduce heat loss and maintain the volume of the liquid for dissolution. This is achieved with tight-fitting plastic lids or film across the opening of the vessels. 

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