Fast dissolving self-nanoemulsifying tablets are hybrid systems that combine two drug delivery systems—SNEDDS (self nano-emulsifying drug delivery systems) and fast dissolving tablet. Therefore, the work presented here includes developing and characterizing the SNEDDS containing a model drug, Ibuprofen, and developing and characterizing the fast dissolving tablets that incorporate the drug loaded SNEDDS.
To develop SNEDDS, the solubilities of Ibuprofen in various oils and surfactants were determined. Based on the pseudo-ternary phase diagrams, two SNNEDS were selected. The droplet sizes with different dilutions and with/without drug loading were measured. The mean droplet sizes were approximately 15 nm, and there was little impact of dilution and drug loading on the mean droplet size.
Five different fast dissolving self-nanoemulsifying tablets were developed with different combinations and ratios of matrix agents (Maltodextrin, Isomalt) and binding agents (PVP K90, succinylated gelatin, HPMC). The lyophilization technique was applied and optimized to create open matrix structures of fast dissolving tablets.
Scanning electron micrographs of five different tablets were taken and showed the highly porous nature and open matrix structures. The mean droplet sizes of nanoemulsions from the five tablets were measured before and after lyophilization, and showed no change, indicating that the nanoemulsion system was stable within the tablets, and the tablets were able to reform nanoemulsions after reconstitution in water. The hardness of the tablets was measured, and the disintegration times were less than 20 seconds. Differential scanning calorimetry studies were performed to detect any physical transformation and determine the glass transition temperature (Tg) of the amorphous tablets. The moisture contents were determined by TGA (thermogravimetric analysis) due to the concern that water molecules could change the texture characteristics and physical integrity of freeze dried tablets.
In this work, pulsatile microdialysis (PMD) as used to sample media in the dissolution tests due to its sensitivity, accuracy, and ability to separate the free drug from the nanoemulsions while still allowing quick and frequent sampling of the dissolution media. This filtering property allowed determination of the free drug concentrations (dissolved or released from the microemulsion) in the dissolution media.
The release of drugs from nanoemulsions is very fast because of the very large surface area associated with these systems, and the dissolved drug concentrations in the dissolution media changed rapidly during dissolution experiments. The dissolution results of five different tablets showed that 90% of the drug was released in 1–2 minutes, and the total released amount is close to 100% in four of the five formulations. The dissolution profiles of the samples subjected to aging remained the same compared with initial samples, indicating the systems were stable. The pH and temperature effects on the dissolution were also studied In addition, dissolution tests with different drug loading by adding more tablets were also performed. Overall, the drug contained in the tablets, if released, could exceed the solubility of the drug in the dissolution medium, resulting in the formation of supersaturated solutions. It was seen that the supersaturated solution remained stable for over a week (i.e., no precipitation of the drug).
To prove this novel drug delivery system is not specific for one drug, the formulation work was conducted again using a second model drug, Indomethacin, and the same physicochemical characterizations were performed. The tablets displayed characteristics similar to those of the tablets loaded with Ibuprofen, and showed a consistent manner to release the Indomethacin into the dissolution media. This indicated that that the drug delivery system developed in this work, fast dissolving self-nanoemulsifying tablets, could be generally applied to poorly soluble drugs to improve the dissolution and bioavailability. (Abstract shortened by UMI.)