Validation of the in-vitro dissolution method used for a new sustained-release theophylline pellet formulation

The in-vitro release method used within the scope of the galenical development of Euphylong pellets and subsequently employed on a routine basis is described. The suitability of the method is demonstrated by means of the validation procedure. The release system used is based on the standard USP XXI apparatus (paddle method) and consists of three essential components: a) dissolution apparatus (paddle model). b) measuring unit (spectrophotometer), c) data acquisition and analysis system. It is demonstrated that in-vitro release rates of theophylline from Euphylong pellets can be accurately investigated with other models as well, since the course of release is not affected by pH value, buffer capacity, surface tension, turbulence of the dissolution medium or agitation by the apparatus. The accuracy of the method as well as its precision and ruggedness are investigated and described. The influences arising from the withdrawal of specimens from the bulk product and of sampling from the release vessel are discussed. The accuracy of the analytical records generated by the computer system is shown and the ruggedness of the analytical program investigated under "worst case conditions". The documentation of the results obtained is described and examined with respect to reliability in the face of system and operating errors. All pertinent guidelines (GAP, FIP guidelines for dissolution testing, etc.) are taken into consideration and their relevance to the above investigation assessed.