Comparison of Dissolution Profiles for Sustained Release Resinates of BCS Class I Drugs Using USP Apparatus 2 and 4: A Technical Note


In vitro dissolution specifications are established to ensure batch-to-batch consistency while pointing out any potential problems with in vivo bioavailability among different drug products (1). At early stages of formulation development, in vitro dissolution testing provides guidance on optimizing drug release from formulations. While at later stages, it may be employed as an indicator of the in vivo performance of drug products to potentially reduce the number of bioavailability/ bioequivalence studies. An established IVIVC can be further used to set meaningful dissolution specifications that take clinical consequences into account in the hope of facilitating regulatory approvals of post approval changes. Among the different in vitro systems available for testing, USP Dissolution apparatus 4 offers a viable option for carrying out dissolution of novel dosage forms (2,3). USP Dissolution apparatus 4 is helpful in: testing robustness of the formulation with respect to the variations in the intralumenal environment, maintaining sink conditions for the poorly soluble drugs (4,5) and non tedious method to change pH of the dissolution medium (6). USP Dissolution apparatus 4 has been extensively studied for the prediction of in vivo performance of orally administered dosage forms like amoxicillin capsules (7), paracetamol (8), carbamazepine (9), danazole capsules (10), spironolactone (11). It is the method of choice for extended release and poorly soluble drugs. Point to point correlation of in vitro release data using flow through cell apparatus is established for monolithic extended release formulations of highly permeable isosorbide-5-mononitrate (12). Similarly, good in vitro in vivo correlation was reported for vincamine extended release formulations (13). The development of flow through cell came about as an attempt to provide controlled hydrodynamic environment and renewable stream to the sample and has proven to be a useful tool in determining the in vitro release of the extended release formulations. Extended release formulation can be formulated using polymer (14), lipids/waxes (15), ion exchange resins (16) etc. Ion exchange resins have recently been gaining importance in pharmaceutical industries in the manufacturing of extended release formulations. IER are water insoluble, cross-linked polymers containing salt forming groups in repeating positions on the polymer chains. IER form a complex with the drug through weak ionic bonding. Drug release from resinate depends on pH and electrolyte concentration within the gastrointestinal tract. With basic drugs, strong cationic exchange resins (sulfonic acid) yield strong drug resin bonding resulting in slower elution of drug from resinates and this principle has exhibited the potential of resins as sustained release agents (17,18). The presence of released drug and ion exchange resin with free active sites has a significant effect on the further release of drug from resinate. This effect will be more pronounced while dealing with BCS class I drugs. Butler et al. (6) has mentioned the usage of USP Dissolution apparatus 4 particularly for drugs with low solubility as it can maintain the sink condition, independent of drug solubility. Hitherto there are no reports in the literature that cite the necessity of maintaining sink conditions while performing in vitro release of sustained release resinates of highly soluble drug. Release data based on a well thought out test is of tremendous value in selection of right formulation. Therefore, the present work was focused on studying the effect of USP Dissolution apparatus 2 and 4 on the in vitro release of drug from resinates of BCS class I drugs.

DOI: 10.1208/s12249-008-9110-4

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@article{Prabhu2008ComparisonOD, title={Comparison of Dissolution Profiles for Sustained Release Resinates of BCS Class I Drugs Using USP Apparatus 2 and 4: A Technical Note}, author={Namita B. Prabhu and Ajit S. Marathe and Satishkumar P. Jain and Pirthi Pal Singh and Kiran Prakash Sawant and Leena Rao and Purnima Dhanraj Amin}, journal={AAPS PharmSciTech}, year={2008}, volume={9}, pages={769-773} }