title: Dissolution kinetics of three-component compressed solid mixtures with largely different solubilities: flaking spheres.
abstract: The dissolution kinetics of three-component compressed solid spheres of various compositions of mannitol (MAN), sulfamethoxazole (SMX), and trimethoprim (TMP) were studied. Because the solubility of MAN was approximately 300 times that of SMX and TMP, the flaking phenomenon during dissolution process was observed. The critical flaking line was drawn between two critical flaking points in the triangular composition diagram of MAN-SMX-TMP mixtures (i.e., the compositions of 0.5022 MAN and 0.4978 SMX mass fractions, and 0.4906 MAN and 0.5094 TMP mass fractions), thus dividing the system into two distinct regions; namely, nonflaking and flaking regions. In the case of nonflaking region, only three dissolution behaviors for MAN-SMX-TMP three-component mixtures were proposed. The calculated dissolution rates of all components by using the multicomponent dissolution model previously proposed were found to satisfactorily approximate the observed values for both two- and three-component solid mixtures. In the case of flaking region, the observed dissolution rate of MAN was found to be the exponential function of the mass fraction ratio of either SMX or TMP to MAN for both two- and three-component mixtures. The slope of the semilogarithmic plot of the observed MAN dissolution rate versus the mass fraction ratio of either SMX or TMP to MAN was defined as retarding coefficients of SMX or TMP, r'(SMX) or r'(TMP), respectively. The erosion rate of either SMX or TMP was the product of mass fraction ratio of drug to MAN and the exponential function of such mass fraction ratio. The mathematical model was developed on the basis of simultaneous erosion followed by dissolution of eroded particles to predict the dissolution rate of each drug from MAN-SMX-TMP compressed solid spheres within the flaking region.
authors.affiliation: Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Road, Bangkok 10400, Thailand. pynst@mahidol.ac.th
authors.forename: N
authors.initials: N
authors.lastname: Sarisuta
authors.forename: S
authors.initials: S
authors.lastname: Jateleela
authors.forename: T
authors.initials: T
authors.lastname: Tourtip
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004338:Drug Combinations; D004339:Drug Compounding; D007700:Kinetics; D008353:Mannitol / Q000737:chemistry*; D008432:Mathematical Computing; D008956:Models, Chemical; D010316:Particle Size; D011208:Powders; D011237:Predictive Value of Tests; D012995:Solubility; D013607:Tablets; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000737:chemistry*
chemical_list: D004338:Drug Combinations; D011208:Powders; D013607:Tablets; D008353:Mannitol; D015662:Trimethoprim, Sulfamethoxazole Drug Combination