Third Generation Solid Dispersion-Based Formulation of Novel Anti-Tubercular Agent Exhibited Improvement in Solubility, Dissolution and Biological Activity.

The long treatment period and development of drug resistance in tuberculosis (TB) necessitates the discovery of new anti-tubercular agents. The drug discovery program of the institute leads to the development of an anti-tubercular lead (IIIM-019), which is an analogue of nitrodihydroimidazooxazole and exhibited promising anti-tubercular action. However, IIIM-019 displays poor aqueous solubility (1.2 µg/mL), which demands suitable dosage form for its efficient oral administration. In the present study, third generation solid dispersion-based formulation was developed to increase the solubility and dissolution of IIIM-019. The solubility profile of IIIM-019 using various polymeric carriers was determined and subsequently, PVP K-30 and P-407 were selected for preparation of binary and ternary solid dispersion. The third-generation ternary solid dispersion comprising PVP K-30 and P-407 revealed a remarkable enhancement in the aqueous solubility of IIIM-019. Physicochemical characterization of the developed formulations was done by employing FTIR spectroscopy, scanning electron microscopy, X-ray diffraction analysis, differential scanning calorimetry, and dynamic light scattering analysis. The dissolution study indicated an impressive release profile with the optimized formulation. The optimized formulation was further examined for cytotoxicity, cellular uptake, and hemolytic activity. The results indicated that the formulation had no apparent cytotoxicity on Caco-2 cells and was non-hemolytic in nature. Moreover, the optimized formulation showed significantly improved anti-tubercular activity compared to the native molecule. These findings showed that the developed third generation ternary solid dispersion could be a promising option for the oral delivery of investigated anti-tubercular molecule.

Recent Advances in the Surfactant and Controlled Release Polymer-based Solid Dispersion.

The oral route is the most preferred delivery route for drug administration due to its advantages, such as lower cost, improved patient compliance, no need for trained personnel, and less severity of drug reactions in general. The major problem with new molecules in the drug discovery pipeline is poor solubility and dissolution rate that ultimately results in low oral bioavailability. Numerous techniques are available for solubility and bioavailability (BA) enhancement, but out of all, solid dispersion (SD) is proven to be the most feasible due to fewer issues in manufacturing, processing, storage, and transportation. In the past few years, SD has been extensively applied to reinforce the common issues of insoluble drugs. Currently, many hydrophobic and hydrophilic polymers are used to prepare either immediate release or controlled release SDs. Therefore, the biological behavior of the SDs is contingent upon the use of appropriate polymeric carriers and methods of preparation. The exploration of novel carriers and methodologies in SD technology leads to improved BA and therapeutic effectiveness. Moreover, the clinical applicability of SD-based formulations has been increased with the discovery of novel polymeric carriers. In this review, emphasis is laid down on the present status of recent generations of SDs (i.e., surfactant and controlled release polymer-based SD) and their application in modifying the physical properties of the drug and modulation of pharmacological response in different ailments.