Fourth-generation Solid Dispersion of Poorly Water-soluble Cefixime Trihydrate: Development and Optimization

Fourth-generation solid dispersion (FG-SD) is the one-step strategy to improve solubility and control drug liberation from the solid dispersion matrix. FG-SD can be developed using a combination of different polymers. In the present work, FG-SD of drug cefixime (CFX) was prepared using a combination of hydrophobic polymers such as cetyl alcohol (CA) and stearic acid (SA), and hydrophilic polymer such as hydroxyl propyl methyl cellulose (HPMC) K4M. CFX belongs to the BCS class IV, indicating poor solubility and poor permeability. Thus, formulation of FG-SD of CFX (FG-SD-CFX) gives a one-step goal that will help to improve the drug CFX solubility and help to manage the drug release in a sustained manner. 12 different formulations were developed using various combinations of HPMC, CA, and SA. The prepared formulation FG-SD-CFX was studied using solubility tests, drug content, and in vitro dissolution studies. The optimized FG-SD-CFX was characterized using Fourier Transform Infrared Spectroscopy (FTIR), Powder X-ray Diffraction (PXRD), and differential scanning calorimetry (DSC). All the formulations developed showed a considerable enhancement in the aqueous solubility of the drug than the plain drugs and exhibited uniform drug content. In vitro studies data reveal that CFX-CA-4 formulation exhibits 93.23% drug release in 24 h. The release kinetics was studied for all the FTIR studies, confirmed that no interactions were observed between the drug and polymers. The PXRD results confirm the formation of an amorphous structure. DSC studies further confirm the conversion of crystalline CFX to an amorphous form, which is supported by the change in ΔH value. Thus, from the study, it can be concluded that the FG-SD is the novel single-step approach that can improve drug release and modify the release of drugs in a sustained manner for the BCS class IV drug CFX. DSC studies confirm the formation of a drug and polymer complex. Thus, from the studies, it can be concluded that FG-SD is an efficient method that can serve a dual purpose of improving the solubility of the drug and sustaining the release in a single step for the drug cefixime.