Compendial methods of dissolution

Compendial methods are the official methods on which the manufacturers rely on.

1. COMPENDIAL METHODS OF DISSOLUTION By- Hemanth KG MPharm Sem II Department of Pharmaceutics

2. Introduction Dissolution is a process in which a solid substance solubilizes in a given solvent i.e. mass transfer from the solid surface to the liquid phase. Bioavailability is defined is defined as the rate and extent (amount) of absorption of unchanged drugs from its dosage form. NEEDS FOR DISSOLUTION TESTING 1. To ensure product quality & performance of manufacturing process. 2 . Requirement for regulatory approval for product marketing.

3. Methods useful in quantitative evaluation of bioavailability can be broadly divided into : I . Pharmacokinetic Methods These are indirect methods . The two major pharmacokinetic methods are: 1. Plasma level-time studies. 2. Urinary excretion studies. II. Pharmacodynamic Methods These methods involve direct measurement of drug effect on a physiological process as a function of time. The two methods are: 1. Acute pharmacological response. 2. Therapeutic response.

4. The best available tool which can quantitatively assure about the biological availability of a drug from its formulation is in-vitro dissolution test Factors influencing the design of dissolution test Factors related to the dissolution apparatus Factors related to the dissolution fluid Process parameters Classification of dissolution apparatus based on presence or absence of sink conditions: Closed compartment apparatus- limited volume apparatus operating under non sink conditions Open compartment apparatus- dosage form is contained in column which is brought in continuous contact with the fresh, flowing dissolution medium i.e., sink conditions

5. USP Apparatus Name of Apparatus Drug Product Apparatus-1 Rotating basket Tablets Apparatus-2 Paddle Tablets, Capsules, Modified release products, Suspensions Apparatus-3 Reciprocating Cylinder Extended release drug products Apparatus-4 Flow cell Low water soluble drugs Apparatus-5 Paddle over disk Transdermal drug products Apparatus-6 Cylinder Transdermal drug products Apparatus-7 Reciprocating disk Extended release drug products Compendial Dissolution Apparatus Types and Their Applications

6. USP apparatus type I (Basket) Dissolution Baskets M esh size ranges from 40 - 10 Common problems associated with the rotating basket test   Clogging Inhomogeneity in the agitation W ire basket corrodes  Low Media Agitation D issolution being accelerated due to abrasion 

7. USP apparatus type II (Paddle) A paddle replaces the basket as the source of agitation The metallic blade and shaft comprise a single entity that may be coated with a suitable inert coating to prevent corrosion.  For 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. 

8. USP apparatus type III (Reciprocating Cylinder) This type is used for modified release dosage forms. It is necessary to obtain a correlation between  in vitro  dissolution results and the bioavailability of these products ( in vitro-in vivo   correlation) So it is essential for the pH, composition, ionic strength, viscosity and agitation speed of the medium to be altered during the dissolution test, thus simulating passage of the product through the gastrointestinal tract . For this purpose the reciprocating cylinder method was developed.

9. The internal cylinders remain in each line of vessels, in reciprocal movement, for pre-programmed times and intensities (dips per minute or " dpm ") in the apparatus. During emersion, the agitation system rises until the screen in the lower cover touches the dosage form, which separates from the screen and floats freely in the dissolution medium when the stirring system activates. After the programmed period, the rods rise until the internal cylinders are positioned over the vessels, where they remain for a pre-established timeframe so that the dissolution medium can drain.

10. USP apparatus type IV (Flow Through Cell) CELLS: Different types of cells are available for testing tablets, powders, suppositories, hard- and soft-gelatin capsules, implants, semisolids, suppositories, and drug-eluting stent Pump and Flow Patterns : Peristaltic and pulsating piston pumps can be used . Usually a sinusoidal pulse rate of 120 ± 10 pulses per minute is used. The pulse rate remains constant independent of the selected flow rate The need for further stirring is eliminated due to the pulsating pattern of the pump Figure 1. Flow through cell

11. The open system is selected for samples that require high volume of media (i.e., low solubility compounds), and the closed system is selected when a low volume of medium is required . Filtration: A filter is at the inner top of the cell to retain undissolved material. Usually glass fiber filters are used. Appropriate selection of the filter is required for efficient filtration and to avoid backpressure created by filter resistance . Sampling: The collected samples can be analyzed directly by a UV vis spectrophotometer or they can be collected in fractions and analyzed by HPLC

12. USP apparatus type V (Paddle Over Disc) 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.

13. USP apparatus type VI (Rotating Cylinder) 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.

14. USP apparatus type VII (Reciprocating Holder) This variant 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. 

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