Drug-release tests

Abrahamsson, B., Johansson, D., Torstensson, A., Wingstrand, K., Evaluation of solubilizers in the drug release testing of hydrophilic matrix extended-release tablets of felodipine, Pharm. Res. 1994, 2 2, 1093-1097. 

Due to the nature of the test method, quality by design is an important qualification aspect for in vitro disolution test equipment. The suitability of the apparatus for the dissolu-tion/drug-release testing depends on both the physical and chemical calibrations which qualifies the equipment for further analysis. Besides the geometrical and dimensional accuracy and precision, as described in USP 27 and Ph.Eur., any irregularities such as vibration or undesired agitation by mechanical imperfection are to be avoided. Temperature of the test medium, rotation speed/flow rate, volume, sampling probes, and procedures need to be monitored periodically. 

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). 

Variation of temperature is usually not an issue for solid oral dosage forms, since experiments are always conducted at body temperature (37°C). For dosage forms applied on the skin, this can be a further consideration e.g., drug-release testing of transdermal products is typically performed at the average temperature of body surface 32°C (5). 

Methods used to determine the performance characteristics of finished products fall into Category III. Dissolution tests (excluding measurement) and drug release tests are examples of these types of methods. Precision is the only parameter required for these methods according to the regulatory guidances, although all validation parameters may be determined based on the intent of the method. 

The USP General Chapters that contain pertinent information regarding dissolution and drug release testing are as follows 5-8... 

An f2 value between 50 and 100 suggests that the two dissolution profiles are similar, indicating the test formulation is bioequivalent to the reference formulation.1 There are a minimum of three timepoints in extended release dosage forms an early timepoint that detects dose dumping, a middle point, and a not-less-than (NLT) 80% point. More points may be added, especially for very long drug release testing periods. 

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. 

A drug release test, dissolution, was a satisfactory standard every time there was a problem of any practical consequence. Of equal significance was the recognition of the strength of dissolution testing as a tool for quality control. Thus, equivalence in dissolution... 

M.M.A. Abdel-Mottaleb, A. Lamprecht, Standardized in vitro drug release test for colloidal drug carriers using modified USP dissolution apparatus I, Drug Dev. Indus. Pharm. 37 (2) (2011) 178-184. 

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