Spray drying of a poorly water-soluble drug nanosuspension for tablet preparation: formulation and process optimization with bioavailability evaluation.
Spray drying experiments of an itraconazole nanosuspension were conducted to generate a dry nanocrystal powder which was subsequently formulated into a tablet formulation for direct compression. The nanosuspension was prepared by high pressure homogenization and characterized for particle-size distribution and surface morphology. A central composite statistical design approach was applied to identify the optimal drug-to-excipient ratio and spray drying temperature. It was demonstrated that the spray drying of a nanosuspension with a mannitol-to-drug mass ratio of 4.5 and at an inlet temperature of 120 °C resulted in a dry powder with the smallest increase in particle size as compared with that of the nanosuspension. X-ray diffraction results indicated that the crystalline structure of the drug was not altered during the spray-drying process. The tablet formulation was identified by determining the micromeritic properties such as flowability and compressibility of the powder mixtures composed of the spray dried nanocrystal powder and other commonly used direct compression excipients. The dissolution rate of the nanocrystal tablets was significantly enhanced and was found to be comparable to that of the marketed Sporanox®. No statistically significant difference in oral absorption between the nanocrystal tablets and Sporanox® capsules was found. In conclusion, the nanosuspension approach is feasible to improve the oral absorption of a BCS Class II drug in a tablet formulation and capable of achieving oral bioavailability equivalent to other well established oral absorption enhancement method.
School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China and.
Wei
W
Sun
Rui
R
Ni
Xin
X
Zhang
Luk Chiu
LC
Li
Shirui
S
Mao
D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004285:Dogs; D005079:Excipients / Q000737:chemistry*; D005240:Feasibility Studies; D017964:Itraconazole / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008353:Mannitol / Q000737:chemistry*; D053758:Nanoparticles; D010316:Particle Size; D011208:Powders; D012995:Solubility; D013607:Tablets; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
D000935:Antifungal Agents; D005079:Excipients; D011208:Powders; D013607:Tablets; D014867:Water; D017964:Itraconazole; D008353:Mannitol
Itraconazole; micrometric properties; nanocrystal; nanosuspension; spray drying