1. Basket Apparatus (USP Apparatus 1): – The basket method was first described in 1968 by Pernarowski, Woo, and Searl. A container, the basket, constrained the enclosed tablet or capsule, allowed for fluid change and could be used either in continuous flow or in restricted volume modes. This gradually evolved to the USP 28 and BP 2004 Apparatus 1—the Rotating Basket Apparatus. The dimensions are taken from the USP 28, although those given in the BP 2004 are similar. The apparatus consists of a motor, a metallic drive shaft, a cylindrical basket, and a covered vessel made of glass or other inert transparent material. The latter should be made of materials that do not sorb or react with the sample tested. The contents are held at 37oC ± 0.5o The vessel is cylindrical with a hemispherical bottom and sides that are flanged at the top. It is 160–175mm high and has an inside diameter of 98–106 mm, and a nominal capacity of 1000 ml. A fitted cover may be used to retard evaporation but should provide sufficient openings to allow ready insertion of a thermometer and allow withdrawal of samples for analysis. The shaft is so positioned that its axis is no more than 2 mm at any point from the vertical axis of the vessel and should rotate smoothly, without significant wobble. The shaft rotation speed should be maintained within ±4% of the rate specified in the individual monograph. The shaft has a vent and three spring clips or other suitable means to fit the basket into position. Each should be fabricated of stainless steel, type 316 or equivalent. Welded seam, stainless steel cloth (40 mesh or 425 mm) is used, unless an alternative is specified. A 2.5 mm thick gold coating on the basket may be used for acidic media. For testing, a dosage unit is placed in a dry basket at the beginning of each test. The distance between the inside bottom of the vessel and the basket is 25 ± 2 mm. The USP 18 described a cylindrical vessel with a slightly concave bottom. The vessel was 16 cm high and 10 cm internal diameter with a nominal capacity of 1000 ml. No precise specifications were given for the concave bottom and differences in tolerances supplied by different manufacturers were common. Consequently, statistically different dissolution rates were obtained for hydrochlorothiazide tablets when determined using containers obtained from two different manufacturers. Flask shape had affected the hydrodynamics of systems and consequently it was considered better to have flasks of uniform hemispherical shape. The flat-bottomed flask described in the BP 1980 alleviated the problems of manufacturing tolerances in vessel shape. Irrespective of apparatus design, there are still several potential problems: –
  • The wire basket corrodes following exposure to acidic media;
  • The basket method gives poor reproducibility due to inhomogeneity of the agitation conditions produced by the rotating basket;
  • And clogging of the basket can occur due to adhering substances. Additionally, particles can fall from the rotating basket and sink to the bottom of the flask where they will not be subjected to the same agitation as that inside the basket.
  • Finally, there is the possibility of dissolution being accelerated due to abrasion of the surface of the dosage form as it rubs against the basket mesh, the so-called ‘‘cheese grater effect.’’
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THE BASKET-STIRRING ELEMENT OF USP 28 (APPARATUS 1)

  1. Paddle Apparatus (USP Apparatus 2):- An apparatus described by Levy and Hayes may be considered the forerunner of the beaker method. It consisted of a 400-ml beaker and a three-blade, centrally placed polyethylene stirrer (5 cm diameter) rotated at 59 rpm in 250 ml of dissolution fluid (0.1N HCl). The tablet was placed down the side of the beaker and samples were removed periodically. In the Apparatus 2,—the paddle apparatus method—a paddle replaces the basket as the source of agitation. As with the basket apparatus, the shaft should position no more than 2 mm at any point from the vertical axis of the vessel and rotate without significant wobble. A distance of 25 ± 2mm between the blade and the inside bottom of the vessel is maintained during the test. The metallic blade and shaft comprise a single entity that may be coated with a suitable inert coating to prevent corrosion. The dosage form is allowed to sink to the bottom of the flask before rotation of the blade commences. In the case of hard-gelatin capsules and other floating dosage forms, a ‘‘sinker’’ is required to weight the sample down until it disintegrates and releases its contents at the bottom of the vessel. The sinker has to hold the capsule in a reproducible and stable position directly below the paddle, but it needs to be constructed in such a fashion that it doesn’t significantly affect hydrodynamic flow within the vessel nor should it appreciably reduce the surface area of the capsule available to the dissolution medium. Two designs have predominated, the three-fingered clip and the helical spring. The former comprises a small circular disc with three short, parallel rods sticking out from it, into which the capsule is wedged. The device is typically plastic but the disc contains metal, which gives it the necessary weight to fall to the bottom of the vessel. The latter is a stainless steel or plastic coated stainless-steel helix (coil, spring) down the middle of which is inserted the capsule. However, with this design, as the thickness of the wire used and the number of turns in the spring increase, the available surface area of the capsule decreases, leading to a concomitant decrease in the observed rate of dissolution. The USP allows for ‘‘a small, loose piece of non-reactive material such as not more than a few turns of wire helix’’ whilst the Japanese Pharmacopoeia (JP) actually prescribes a specific sinker.

 

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TYPICAL SINKER DESIGNS. (A) 3-PRONG SINKER; (B) JP BASKET SINKER; AND (C) HELICAL-SPRING SINKER.

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THE PADDLE-STIRRING ELEMENT OF USP 28 (APPARATUS 2).

  1. Reciprocating Cylinder Apparatus (USP Apparatus 3):- An apparatus comprising vertically reciprocating tubes sealed with mesh discs at each end to restrain the dosage form is official in USP 28 as the Reciprocating Cylinder Apparatus. This has been commercially developed as the Bio-Dis apparatus, which allows tubes containing the sample to be plunged up and down in a small vessel containing the dissolution medium. It has been designed to allow the tubes to be dipped sequentially in up to six different media vessels, using programs that vary the speed and duration of immersion. It allows automated testing for up to six days and the manufacturers advocate its use in the testing of extended-release dosage forms. It became official in USP 22 as Apparatus 3 and is prescribed for the testing of extended-release articles. However, there is some evidence that samples tested using this apparatus tend to yield higher values of amount released than might be found using alternative procedures.

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THE RECIPROCATING CYLINDER APPARATUS OF USP 28 (APPARATUS 3).

  1. Flow-Through Cell Apparatus (USP Apparatus 4): – Limited-volume apparatus with a finite volume of dissolution fluid suffer from the problem that they operate under non-sink conditions, which results in limitations when poorly soluble drugs are considered. A flow-through system and reservoir may be used to provide sink conditions by continually removing solvent and replacing it with fresh solvent. Alternatively, continuous re-circulation may be used when sink conditions are not required. The drawbacks of nonflow- through apparatus include:

(i) lack of flexibility;

(ii) Lack of homogeneity;

(iii) The establishment of concentration gradients;

(iv) Their semi-quantitative agitation;

(v) The obscuring of details of the dissolution processes; and

(vi) Their variable shear.

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SCHEMATIC DIAGRAM OF A FLOW-THROUGH DISSOLUTION CELL

Consequently, the flow-through apparatus has been developed, which features a dissolution cell of low volume (often <30 ml) and a reservoir to provide fresh solvent. This is official in USP 28 as USP Apparatus 4 where it is prescribed for testing extended-release articles. The basic components are reservoir, pump, heat exchanger, column (cell), tablet support, filter system, and analytical method. The systems enable solvent to be taken from a suitable reservoir and passed straight through the apparatus containing the dosage form to be either assayed and removed (effluent system) or recirculated (recycling system). The design of the pump to remove the solvent from the reservoir is crucial to the results obtained from such systems. The pump used may be either a displacement (oscillating or peristaltic) or a momentum (centrifugal) type. However, peristaltic pumps may create oscillations that might result in faster dissolution rates than might otherwise have occurred. Dissolution is affected by factors such as the volumetric flow rate, the cross-sectional area of the cell, the initial drug quantity, liquid velocity, and drug concentration. The maintenance of a controlled flow is crucial to column methods and can be influenced by the inlet system. Laminar flow of solvent through the cell is achieved by placing glass beads at the bottom of the cell to facilitate similar disintegration of all surfaces of the sample. It is common to place the tablets on such supports, but attrition (by glass beads) may encourage breakdown of the dosage form thereby increasing dissolution rates. Tablet support and consistent positioning in the liquid flow are prerequisites for consistent results. Consequently, attempts have been made to embed the tablet in glass wool or glass beads.

Laminar flow conditions are typically used for tablets, hard gelatin capsules, powders, and granules.

Suppositories and soft gelatin capsules are placed in the cell without beads for turbulent flow.

Flow-through facilities can be constructed from cylindrical chromatographic columns with flow-rates as low as 1 ml/min. Ascending flow minimizes the problems associated with air bubbles and allows laminar flow of the solvent and ascending columns are the most common types of flow-through apparatus. The columns may be short with tapered inlet and outlet sections but generally are long sections of straight-sided tubing to provide hydrodynamic stability to the liquid flow. The material under test is placed in the vertically mounted dissolution cell, which permits solvent at 37oC ± 0.5oC to be pumped in from the bottom. The cell type selected is dependent on the dosage form being tested. Standard cells used for tablets and capsules have an internal diameter of 12 mm but may show a higher dissolution rate when compared to 26mm cells due to higher flow velocity.

For testing powders and granules, a modified cell containing two screen plates is used where the sample is placed between the screen plates.

The suppository cell is designed for use with suppositories and soft gelatin capsules. Fats and gels used in these dosage forms are separated in this type of cell so as not to block the filters.

The cell for implants has a 1 ml volume due to the low flow rates (e.g., 5 ml/hr) required for testing this dosage form in a test that may continue over several weeks.

The flow rate of the dissolution medium through the cell must be specified for each product. The USP recommends a flow rate between 4 and 16 ml/min with an allowance of ±5%.

Manual operation and sampling for this type of test can be tedious and the system can be automated to control the pump, heat exchanger and test procedure, and deliver samples to a fraction collector. The system can be programmed to switch between different media at predetermined time points to allow pH changes during the test.

Further advantages of the flow through method include:

(i) Selection of laminar or turbulent solvent flow conditions;

(ii) Simple manipulation of medium pH to match physiological conditions;

(iii) Application to a wide range of dosage forms e.g., tablets, hard and soft gelatin capsules, powders, granules, implants, and suppositories. Whilst the applicability of the flow through apparatus to bio relevant dissolution tests still requires further investigation and optimization, an in vitro–in vivo correlation (IVIVC) has been reported with this apparatus using physiologically relevant flow rates and media.

  1. Paddle-over-Disk Apparatus (USP Apparatus 5): – This uses the paddle apparatus (USP 2) with the sample, usually a transdermal delivery system, being attached to a stainless-steel disk, which is then placed on the bottom of the vessel, directly under the paddle.

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  1. Rotating Cylinder Apparatus (USP Apparatus 6):- This is a modification of the basket apparatus (USP Apparatus 1) with the basket being replaced by a stainless steel cylinder. The sample is again usually a transdermal delivery system attached to the outside of the cylinder.

 

  1. Reciprocating Holder Apparatus (USP Apparatus 7): – 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 Pseudoephedrine hydrochloride extended-release tablets USP where the tablets are enclosed in a 5×5 cm2 of nylon, which is then attached to the rod.NJNJNJ

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  1. Reciprocating Cylinder Apparatus (USP Apparatus 3):- An apparatus comprising vertically reciprocating tubes sealed with mesh discs at each end to restrain the dosage form is official in USP 28 as the Reciprocating Cylinder Apparatus. This has been commercially developed as the Bio-Dis apparatus, which allows tubes containing the sample to be plunged up and down in a small vessel containing the dissolution medium. It has been designed to allow the tubes to be dipped sequentially in up to six different media vessels, using programs that vary the speed and duration of immersion. It allows automated testing for up to six days and the manufacturers advocate its use in the testing of extended-release dosage forms. It became official in USP 22 as Apparatus 3 and is prescribed for the testing of extended-release articles. However, there is some evidence that samples tested using this apparatus tend to yield higher values of amount released than might be found using alternative procedures.

 

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 Reference links

 http://www.pharmalearners.com/2015/06/25/dissolution-apparatus-types-applications-per-usp/

http://www.pharmatips.in/Articles/Pharmaceutics/Tablet/Drug-Dissolution-Apparatus-I-USP-Rotating-Basket.aspx