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


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.
a State Key Laboratory of Ophthalmology , Zhongshan Ophthalmic Center, Sun Yat-sen University , Guangzhou , China.
Mei
M
Yang
a State Key Laboratory of Ophthalmology , Zhongshan Ophthalmic Center, Sun Yat-sen University , Guangzhou , China.
Yang-Fan
YF
Yang
b School of Pharmaceutical Sciences , Sun Yat-sen University , Guangzhou , China.
Ming
M
Lei
a State Key Laboratory of Ophthalmology , Zhongshan Ophthalmic Center, Sun Yat-sen University , Guangzhou , China.
Cheng-Tian
CT
Ye
b School of Pharmaceutical Sciences , Sun Yat-sen University , Guangzhou , China.
Chun-Shun
CS
Zhao
a State Key Laboratory of Ophthalmology , Zhongshan Ophthalmic Center, Sun Yat-sen University , Guangzhou , China.
Jian-Gang
JG
Xu
a State Key Laboratory of Ophthalmology , Zhongshan Ophthalmic Center, Sun Yat-sen University , Guangzhou , China.
Kai-Li
KL
Wu
a State Key Laboratory of Ophthalmology , Zhongshan Ophthalmic Center, Sun Yat-sen University , Guangzhou , China.
Min-Bin
MB
Yu
D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D065347:Hypromellose Derivatives / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011728:Pyridones / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011817:Rabbits; D014783:Viscosity
D009883:Ophthalmic Solutions; D019999:Pharmaceutical Solutions; D011728:Pyridones; D065347:Hypromellose Derivatives; C093844:pirfenidone
Anti-scarring; HPMC-based solution; ocular drug delivery; pirfenidone; rheology