Itraconazole Feasibility Study

Itraconazole, a BCS Class II drug has poor aqueous solubility leading to poor bioavailability. The objective of the present investigation was to formulate Itraconazole Liquisolid compacts to enhance its oral bioavailability. Optimized formulation was prepared using PEG 600 as non-volatile solvent, Alfacel PH 200 as carrier and Aerosil 200 as coating material by using Mathematical model for designing the liquisolid systems. The free flowing dry powder blend was then compressed into tablets and evaluated for various parameters. Precompression and post compression parameters were within the acceptable limits. Optimized formulation showed higher drug dissolution with 90.73% in 90 minutes as compared to conventional tablet and marketed capsule.

The oral route remains preferred route of drug administration due to its convenience, good patient compliance, cost effectiveness and many other advantages. For the poorly water soluble drugs, the dissolution process acts as the rate-controlling step which determines the rate and extent of absorption. Consequently, many hydrophobic drugs show erratic and incomplete absorption from the GIT. Thus, one of the major challenges in drug development today is to overcome the problem of poor solubility of the active ingredient [1, 2]. Itraconazole is a potent broad spectrum Triazole antifungal agent with the absolute bioavailability of 55%. The bioavailability is reduced to 40% when administered under fasting conditions[3]. The principal reason of poor bioavailability is its low aqueous solubility (9.64 µg/ml) [4, 5]. The marketed formulations of Itraconazole consist of solution and capsule. Oral solution contains 10 mg Itraconazole per ml solubilized by HP-beta-cyclodextrin (400 mg/ml) as a molecular inclusion complex. The high content of HP-beta-cyclodextrin in this formulation causes osmotic diarrhoea. The capsule form is a molecular dispersion of drug in amorphous HPMC but it shows relatively low bioavailability ( ̴ 40%) after oral administration because of its poor solubility and incomplete absorption [6]. Another limitation of Itraconazole is its poor flow property and compressibility and is

In this technique poorly soluble API dissolved in a non volatile solvent (with high boiling point such as propylene glycol, liquid polyethylene glycols and glycerin) may be transformed into a free flowing, readily compressible and apparently dry powder by simple physical blending with selected excipients named the carrier and coating material. This dry powder is later compressed into tablet or filled into capsule [28]. Since the drug remains in solubilized state in non volatile solvents when administered, its dissoultion rate is improved. The simple manufacturing process, low production costs makes it a feasible technique for industrial production. The present investigation aimed at achieving dual objectives of enhanced bioavailability and improvement in flowability and compressibility leading to a possibility of tablet preparation by direct