Evaluation and comparison of dissolution data derived from different modified release dosage forms: an alternative method.
Dissolution testing is an essential requirement for the development, establishment of in vitro dissolution and in vivo performance (IVIVR), registration and quality control of solid oral dosage forms. The objective of the present study was to investigate the effect of delivery system positioning in accordance with the USP 23-recommended dissolution methods and the proposed modification on drug release from controlled release systems having different operating release mechanisms, namely, swellable floatable, swellable sticking and osmotic pump. The delivery systems were evaluated by placing each dosage form either in the dissolution vessel in accordance with the USP 23 methods or over/below a designed ring/mesh device for achieving full surface exposure to the dissolution medium for sticking or floatable systems respectively. Results indicate that the overall release profiles from the sticking and floatable systems of theophylline are sensitive to their positioning in the dissolution vessel (P<0.05). Furthermore, release of diltiazem hydrochloride from the sticking system also demonstrated sensitivity (P<0.05). In contrast, the floatable dosage form of this latter drug with the application of a helical wire sinker, or when it was placed below the ring/mesh assembly, or by allowing the dosage form to float, did not show sensitivity (P>0.05) for the overall release behavior. This was attributed to the greater solubility of diltiazem hydrochloride (50% solubility in water at 25 degreesC) in comparison to theophylline which is a sparingly soluble drug (0.85% solubility in water at 25 degreesC). Drug release from the osmotic pump appeared to be identical under the given experimental conditions (P>0.05). Statistical analysis of data was performed by comparing the t50%, t70%, t90%; mean dissolution times (MDT50%, MDT70%, MDT90%); the "difference factor, f1" and "similarity factor, f2". It is concluded that the results derived from the application of the "similarity factor, f2" are superior to the individual time points (e.g. tx%) and MDTx% values in differentiating between overall release patterns or the border line release profile differences. It also became apparent that in the case of the swellable sticking systems full surface exposure to the dissolution medium results in greater release rate. For the osmotic pump the required osmotic pressure threshold necessary for constant rate drug delivery appears to have reached independent of the hydrodynamic conditions. A successful and more accurate evaluation of dissolution data can be derived when full surface exposure is considered and this can be accomplished by dissolution method modification with the aid of the designed ring/mesh assembly.
Pillay
V
V
Temple University, School of Pharmacy, Department of Pharmaceutical Sciences, 3307 North Broad Street, Philadelphia, PA 19140, USA.
Fassihi
R
R
D000465:Algorithms; D002626:Chemistry, Pharmaceutical / Q000706:statistics & numerical data*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives; D009543:Nifedipine / Q000737:chemistry; D009994:Osmolar Concentration; D012995:Solubility; D013806:Theophylline / Q000737:chemistry
D003692:Delayed-Action Preparations; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D013806:Theophylline; D009543:Nifedipine