Preparation and evaluation of HPMC-based pirfenidone solution in vivo.

CONTEXT: Pirfenidone (PFD) has exhibited therapeutic potential in the treatment of cell proliferative disorders. The previously developed 0.5% water-based PFD eye drops by our team exhibited antiscarring effectiveness and ocular safety but with a limit of short half-life and poor bioavailability. OBJECTIVE: To increase bioavailability of the water-based PFD eye drops, we prepared a viscous solution by adding hydroxypropyl methylcellulose (HPMC, F4M), which acted as a viscosity-enhancer. Subsequently, we compared the HPMC-based PFD solution with the water-based PFD eye drops. MATERIALS AND METHODS: PFD solution with 1% HPMC (w/v) was prepared, and the viscosities at different shear rates were measured to investigate its rheology. PFD concentrations in the tear, aqueous humor, conjunctiva, cornea, and sclerae of New Zealand rabbits were detected at different time points with high-performance liquid chromatography (HPLC) following single instillation of the 0.5% PFD (w/v) water-based eye drops or HPMC-based solution. RESULTS: Compared with the 0.5% water-based PFD eye drops, the HPMC-based solution increased the PFD levels in tears and prolonged the residence time from 10 to more than 20 min (p < .01). Consequently, the concentrations of PFD in aqueous humor, conjunctiva, cornea, and sclera were elevated to varying degrees until 90 min after topical administration. CONCLUSIONS: The developed formulation possesses a same readily administration and simple preparation as the PFD eye drops; however, the HPMC-based solution exhibited the higher bioavailability.

[Assessment of Pueraria lobata isoflavone with self-microemulsifying drug delivery systems in vitro and in vivo].

OBJECTIVE: To evaluate the self-microemulsifying ability and dissolution behavior of pueraria lobata isoflavone in vitro and the pharmacokinetic behavior in rats. METHODS: The self-microemulsifying rate was evaluated by the self-microemulsifying time and the self-microemulsifying efficiency was evaluated by the particle size of resultant microemulsions. The plasma concentrations were evaluated by HPLC and dissolution and pharmacokinetic behavior of self-microemulsifying drug delivery systems were evaluated by comparison with commercial tablets. RESULTS: The system was self-microemulsified in 2 min and the particle size was less than 50 nm. The dis- solution of SMESC in distilled water was more than 90% at 10 min, while those of the commercial tablet were less than 50% at 120 min. 82% increase in the relative bioavailability was observed for the self microemulsifying drug delivery systems compared with Yufengningxin tablets. Tmax was smaller in the self-microemulsifying drug delivery systems compared with Yufengningxin tablets. CONCLUSION: The self-microemulsifying drug delivery systems can increase drug dissolution in vitro and absorption in vivo significantly.