RESUMO
Solubility of pharmaceuticals is still a challenging subject and solubilization using cosolvents is the most common technique used in the pharmaceutical industry. The purpose of this study was reporting and modeling the experimental molar solubility of pioglitazone hydrochloride [PGZ-HC1] in binary and ternary mixtures of ethanol [EtOH], N-methyl pyrrolidone [NMP], polyethylene glycols [PEGs] 200, 400, 600 and water along with the density of saturated solutions at 298.2 K. To provide a computational method, the Jouyban-Acree model was fitted to the solubilities of the binary solvents, and solubilities of the ternary solvents were back-calculated by employing the solubility data in mono-solvents. In the next step, the ternary interaction terms were added to the model and the prediction overall mean percentage deviation [MPD] of the ternary data was reduced. Also a previously proposed version of the model was used to predict the solubility of PGZ-HC1 in binary and ternary mixtures employing the experimental solubility data in mono-solvents. The overall MPD of the model for fitting the binary data and predicted data of ternary solvents were 2.0% and 50.5%, respectively. The overall MPD of the predicted solubilities in ternary solvents using the ternary interaction terms in the model was 34.2%, and by using the proposed version of the Jouyban-Acree model for binary and ternary data the overall correlation and prediction errors were 18.0 and 15.0%, respectively. The solubility of PGZ-HC1 was increased by addition of EtOH, NMP, PEGs 200, 400 and 600 to aqueous solutions. The reported data extended the available solubility data of pharmaceuticals which are crucial in formulation of liquid dosage forms. The constants of the Jouyban-Acree model using the generated data are also reported which provides the possibility of solubility prediction in other solvent mixtures and temperatures
RESUMO
Several methods are available for control release of propranolol hydrochloride [PLH]. The aim of the present study was to develop a novel technique to sustain PLH release from matrices. Matrices of PLH containing sodium carboxymethylcellulose [Na CMC] and various amounts of the inorganic cations Ca[2+] and A1[3+] were prepared. Dissolution of the matrices was carried out using the USP apparatus I. Analysis of release data was performed by some model independent and dependent approaches. The release of PLH was affected by incorporation of different amounts [milliequivalents, meq] of Ca[2+] 2+ and Al[3+]. When the Ca[2+] amount increased from 0- 0.375 meq, the fraction of PLH which released within 480 min was augmented from 0.74 to 1 apparently via disintegrating effect of the cation. Al[3+] in the range 0- 0.125 meq, decreased the fractional release from 0.74 to 0.37 presumably by in situ cross- linking with polymer. Al[3+] between 0.125 and 0.5 meq enhanced the release from 0.37 to 1 possibly due to the disintegrating effect. Among model independent metrics, the mean release time [MRT] failed to represent the effect of the cations on the release but the release efficiency [RE] as well as a suggested mean release rate [MRR] correlated well with the experimental release rate. Due to the complexity of the release, the only suitable kinetic model was the Weibull distribution. The minimum and maximum Weibull release rate constants for matrices containing Al[3+] were 0.0007-0.017 1/min. The corresponding values for the matrices with Ca[2+] were 0.0029-0.0082 1/min. Through careful choice of the amount of Al[3+] in NaCMC matrices the release of PLH can be controlled at a desired rate. The best model independent approach is MRR and the most accurate model dependent method is Weibull distribution to describe the release data