The Comparison of In Vitro Release Methods for the Evaluation of Oxytocin Release from Pluronic® F127 Parenteral Formulations

The objective of these studies was to develop a discriminatory in vitro release test for assessing formulation factors that may affect oxytocin (OT) release during formulation development studies of a Pluronic® F127 OT in situ gel-forming parenteral dosage form. An appropriate release assessment method should be able to discriminate between the performance of different formulation compositions (1, 2), and this was the primary criterion used for selection of an appropriate test procedure during the test method development process. ANOVA and the difference (f1) and similarity (f2) factors were used to evaluate the discriminatory behavior of different test methods that were investigated in these studies. The in vitro release tests that were investigated included the use of USP Apparatus 1, 2, and 3; a dialysis bag in USP Apparatus 2; and a membrane-less diffusion method. It was concluded that the use of USP Apparatus 3 was best able to discriminate between OT release for the different formulations tested. USP Apparatus 3 was thus considered the most suitable in vitro release test apparatus for studying formulation factors affecting OT release during the development of a parenteral dosage form prepared using Pluronic® F127. purposes, batch uniformity assessment, and evaluating batch-to-batch variability. In the context of pharmaceutical research and development, prediction of in vivo behavior of dosage forms and assessment of the impact of formulation changes or method of manufacture on overall dosage form performance in vivo may be inferred from dissolution profiles (9). The intrinsic variability of in vitro release testing warrants careful method development for a test to reflect the true drug release characteristics from any drug delivery system. The type of drug and apparatus that are used must be carefully considered, since these factors can influence the rate and extent of drug release obtained during in vitro release testing (10). The selection of an in vitro release method and dissolution medium must allow for the prediction of an in vitro–in vivo correlation for the ultimate method of choice, if at all possible (11). There are no accepted compendial guidelines for in vitro testing to assess drug release for controlled and sustained release parenteral formulations, such as those made from PF-127, for example. The United States Pharmacopeia (12) provides guidance for dissolution testing of oral and transdermal dosage forms but not for assessing the in vitro release of an active ingredient from controlled release parenteral preparations. Guidelines for the evaluation of novel delivery systems such as orally disintegrating and chewable tablets have been reported, although recommendations for controlled release parenteral formulations have not yet been established. However, the use of compendial and modified flow-thorough cell apparatus for assessment of sustained Corresponding author. diss-14-04-05.indd 15 11/8/2007 1:55:42 PM dx.doi.org/10.14227/DT140407P15