Dissolution Stability Study of Cefadroxil Extemporaneous Suspensions

Dissolution studies have become matter of great significance because, in most cases, drug dissolution is the rate-limiting step in the absorption process. As occurs with solid oral dosage forms, heterogeneous disperse systems (suspensions) could also have some problems with their in vitro dissolution. The dissolution behavior of four different brands of cefadroxil extemporaneous suspensions available in the Argentinian market was evaluated. The deliverable volume, pH, visual appearance, uniformity of dosage units, and assay were also studied. Powders for oral suspension were stored under different aging conditions. Samples at room temperature and refrigerated conditions were taken at several time points to carry out the dissolution stability study during the expiration period of the reconstituted form. Marked differences were recorded with respect to in vitro dissolution behavior between the different products under evaluation. e-mail: [email protected] when drug particle dissolution is a requirement for bioavailability and, in most cases, the rate-limiting step in absorption (6). In fact, the 1987 FDA Stability Guideline (7) specifically called for dissolution testing of suspensions (Section III.B.6.d). However, there are only a few compendial requirements in pharmacopeial sources for suspension dissolution studies. The United States Pharmacopeia (8) contains 98 monographs for oral suspensions, but only seven of them have a codified dissolution test. Studies carried out on suspension dissolution (6, 9–15) did not consider if there were any change in this process during the administration period of the reconstituted suspension (stored at room temperature as well as under refrigeration) throughout the shelf life of the powdered product. Dissolution stability is considered a critical parameter not only from the standpoint of quality control, but also for the impact on the bioavailability of the product, because significant changes of in vitro release profile during storage affect bioavailability. During aging, the absence of dissolution changes provides some assurance that the bioavailability remains intact (5). Cephalosporins are widely used in suspension dosage forms and are one of the safest and most effective broad-spectrum bactericidal agents. Cefadroxil is a semisynthetic, first-generation cephalosporin antibiotic, the p-hydroxy derivative of cephalexin, with a potential activity against many moderate to mild bacterial infections including staphylococci, streptococci, and enterobacteriae (16). It is slightly soluble in water and in alcohol (16, 17). It is well absorbed from the Corresponding author. INTRODUCTION Many patients, especially geriatric and pediatric patients, have difficulty swallowing whole solid oral dosage forms. An effective pharmaceutical dosage form should be considered as a dosing device to enable the accurate and repetitive dosing of drugs. Extemporaneous suspensions, like many other dosage forms, are much more than simple drug carriers, since they may affect the absorption rate and the effectiveness in the patient. Most of the problems linked with this pharmaceutical form are associated with its physical stability and include dosing accuracy, unknown bioavailability, and lack of access to modified release preparations for pediatric patients, among others (1). There are few stability studies undertaken on extemporaneous products (1). In this disperse type system, physical change is more important than chemical change. However, it is assumed that suspension stability is primarily governed by the decomposition of the drug dissolved in the aqueous phase (2). In general, suspension stability determinations consider only factors like changes in chemical stability, visual appearance, pH, caking, and re-dispersability (3, 4), with no focus on Dissolution Stability. This term refers to the retention of the dissolution behavior of the dosage form from manufacture to the expiration date (5). Since suspensions are similar to the disintegrated form of tablets, in vitro dissolution studies are also essential diss-15-03-09.indd 29 8/6/2008 2:07:25 PM dx.doi.org/10.14227/DT150308P29