Evaluation of Dissolution Media Containing a Novel Synthetic Surfactant by In Vitro Testing of BCS Class II Drugs

The objective of this study was to employ a tailor-made, surface-active agent (phosphonobile acid) in the design of dissolution media that more closely reflect various luminal fluid physicochemical parameters such as buffer capacity, osmolarity, surface tension, and pH. The proposed media are simple to prepare and use, and thus can be explored for routine application. Three BCS II drugs, glimepiride, dipyridamole, and ibuprofen, were selected for the study. In vitro dissolution profiles obtained with the proposed media were compared with profiles obtained in FaSSIF and FeSSIF media using the f2 similarity factor. Dissolution in the proposed media correlate well with the dissolution obtained in FaSSIF and FeSSIF media. INTRODUCTION The science of dissolution is centuries old, and the application of dissolution testing is very important during drug development and the submission process for NDA and ANDA filings. Dissolution of drugs from oral solid dosage forms is a necessary criterion for drug bioavailability (i.e., the drug must be solubilized in the aqueous environment of the gastrointestinal tract to be absorbed). Therefore, the dissolution test for solid oral drug products has emerged as one of the most important control tests for assuring product uniformity and batchto-batch bioequivalence once bioavailability has been defined. Various pharmacopoeias suggest that the dissolution characteristics of an oral formulation should be evaluated in the physiologic pH range of 1.2–6.8 (1.2–7.5 for modified-release formulations) (1). However, poorly water-soluble compounds fail to solubilize in dissolution media over the entire pH range of 1.2–6.8. The determination of dissolution profiles of waterinsoluble or sparingly water-soluble compounds requires dissolution media different from those normally used for water-soluble drugs. Water-insoluble or sparingly water-soluble drug products are most likely to solubilize in the presence of the naturally occurring surfactant and micellar media of the gastrointestinal tract. Buri et al. (2) demonstrated the similarity of natural surfactants (sodium cholate and taurocholate) to sodium lauryl sulfate (SLS) for the purpose of drug solubilization. The dissolution of water-insoluble and sparingly watersoluble drug dosage forms was studied with the use of surfactant-like SLS (3, 4); these reports suggest the use and importance of surfactants for in vitro dissolution studies. In addition to SLS, other surfactants like Tween or Span are also used in dissolution media for quality control tests (1). Routinely used dissolution media are mainly employed to check the batch-to-batch reproducibility of dosage forms. The designs of various reported dissolution media that have been characterized as “biorelevant media” were based on the physiological condition of the gastrointestinal tract containing sodium taurocholate as a surfactant (5–10). However, because of the high expense of these natural products, they are not practical to use in routine quality control tests. Use of SLS in dissolution media for poorly water-soluble drugs is based mainly on the solubilization capacity of this synthetic surfactant, but SLS lacks the physiological relevance of the gastrointestinal tract. Dissolution profiles obtained using synthetic surfactants like SLS may or may not exhibit IVIVC (4). To the best of our knowledge, synthetic surfactants with structural similarity to bile acids have not been reported. In the present work, our primary aim was to select a synthetic surfactant that has structural similarity to bile acids. 24-Phosphonobile acid (24-PBS) was selected as a suitable candidate. The use of 24-PBS as a cholesterol gallstone solubilizer and its route of synthesis have been reported (11). The selected synthetic surfactant was used to design dissolution media that simulate the physiological properties of the luminal fluids such as buffer capacity, pH, osmolarity, and surface tension. The evaluation of the proposed media was done using three BCS Class II drugs. The dissolution results obtained with the proposed media were statistically compared with the results obtained using two commonly used biorelevant dissolution media, Fasted-State Simulated Intestinal Fluid (FaSSIF) and Fed-State Simulated Intestinal Fluid (FeSSIF), using the f2 similarity factor (12). Corresponding author. diss-16-03-03.indd 14 8/26/2009 2:44:35 PM dx.doi.org/10.14227/DT160309P14