Solubility Enhancement of Tadalafil Drug by Nano-Cocrystallization Technique

The purpose of the present work was to enhance the solubility of water-insoluble tadalafil drug by nano-cocrystallization method. The nano-sized cocrystals of tadalafil were prepared by solvent-antisolvent precipitation technique, where ethanol was used as a solvent for the drug and water as an anti-solvent in the process. The precipitated suspension was dried by rotary vacuum evaporation of controlled temperature to obtain nano-cocrystals. By this method, nano-cocrystals of tadalafil with different co-formers like benzoic acid, citric acid, vanillic acid and gallic acid were prepared in the stoichiometric ratio of 1:1, 1:1.5 and 1:2. Poloxamer-188 and Tweens-80 were incorporated as stabilizer and surfactant respectively in a concentration equivalent to weight ratios of drug: stabilizer at 1:0.5 and drug: surfactant at 1:0.3. The compatibility of the drug with coformers, stabilizer and surfactant was established using FT-IR spectroscopy. The nano-cocrystals prepared were characterized for solubility profile, melting point, microscopy, particle size distribution, x-ray diffraction and scanning electron microscopy. All the nano-cocrystals prepared were shown an increase in solubility and decrease in melting point. Microscopic image of the pure drug in compared with different nano-cocrystals prepared were showing significant difference with the specific shape and size. In XRD, the emergence of a new peak position compared to the pure drug indicates the formation of a new crystalline phase. The particle size distribution results prove that the formed crystals are in the nano range to comply with the sizes below micron. Nano-crystallization of tadalafil with selected coformers, stabilizers and surfactants enhance its solubility into manifolds and hence, this approach can be used as an alternate approach to conventional methods of solubility enhancement of BCS class II drugs like particle size reduction, milling, use of solubility enhancers, etc. Also, the developed nano-cocrystals replaces the use of insoluble tadalafil as such in pharmaceutical dosage forms like tablets or capsules. The present work demonstrated that low-temperature anti-solvent precipitation technique has excellent potential to prepare nano-cocrystals with improved solubility and a higher bioavailability.