He selected model OMS material due to Idarubicin Topoisomerase inhibitor its thicker walls and higher degree of silica condensation which results in its greater resistance to compression. Polyvinylpyrrolidone was selected as the binding agent due to its widespread use as a binder in wet granulation. Our hypothesis is that wet granulation is a suitable technique to improve powder flow and compactibility of OMS. However, careful considerations of the process parameters must be made to avoid premature drug release from the pores during the granulation step. Evaluation of four poorly water soluble compounds, itraconazole, fenofibrate, naproxen, and ibuprofen revealed that the risk of premature drug release during granulation is primarily compound dependent. Using ITZ loaded COK 12 for primary assessments, various concentrations of binder in solution, type of solvent, and flow rate addition were assessed. A correlation between improved compactibility and processing temperature was also established. Furthermore, powder flow of the agglomerated material improved based on Carr Index and Hausner Ratio results. 2. Materials and methods 2.1. Model compounds Table 1 lists the physicochemical properties of the selected Class II compounds from the Biopharmaceutical Classification System. Itraconazole belongs to the triazole group of antifungal agents against histoplasmosis, blastomycosis, and onychomycosis. Fenofibrate improves cholesterol levels by decreasing low density lipoprotein and very low density lipoprotein levels while increasing high density lipoprotein. Naproxen and ibuprofen are both non steroidal anti inflammatory drugs. 2.2. Synthesis procedure COK 12 was synthesized according to the procedure described by Jammaer et al. Here, 4.0 g of Pluronic P123 was dissolved in 107.5 g deionized water under stirring following the addition of 3.7 g citric acid monohydrate and 2.5 g trisodium citrate.
The resulting surfactant solution was stirred for 24 h. Next, 10.4 g of sodium silicate solution was diluted with 30.0 g of water and added to the surfactant solution. The pH was measured prior to and after the sodium silicate addition using a Mettler Toledo, InLabExpert Pro pH electrode. The final mixture was stirred for 5 min at 175 rpm with a mechanical stirrer and kept at room Candesartan 139481-59-7 temperature under static synthesis conditions for 24 h. The synthesized material was then filtered, dried at 80 C, and calcined in two steps: 8 h at 300 C and 8 h at 500 C with a 1 C/min heating rate. 2.3. N2 Adsorption desorption isotherms Nitrogen adsorption isotherms of all silica materials were determined at 196 C using a Micrometrics Tristar II 3020 apparatus. Samples were pre treated overnight at, respectively, 110 C and 250 C for itraconazole loaded and non loaded OMS, under nitrogen flush. The pore volume and the surface area was calculated using the t plot method of Jaroniec and Kruk. The mesopore size distribution of each sample was derived from the adsorption branch of its nitrogen isotherm using the Barret Joyner Halenda model. Samples were analyzed as n 1. 2.4. Drug loading All compounds were loaded into COK 12 using the incipient wetness impregnation procedure which infuses the drug into the pores through capillary forces. Loading solutions were prepared as follows: 50 mg/ml in dichloromethane for it.