Influence of drug loading and type of ointment base on the in vitro performance of acyclovir ophthalmic ointment.
The availability of in vitro performance tests such as in vitro drug release testing (IVRT) and in vitro permeation testing (IVPT) are critical to comprehensively assure consistent delivery of the active component(s) from semisolid ophthalmic drug products. The objective was to study the impact of drug loading and type of ointment base on the in vitro performance (IVRT and IVPT) of ophthalmic ointments using acyclovir as a model drug candidate. The in vitro drug release for the ointments was evaluated using a modified USP apparatus 2 with Enhancer cells. The transcorneal permeation was carried out using rabbit cornea on modified vertical Franz cells. The drug retention in cornea (DRC) was also determined at the end of transcorneal drug permeation study. The in vitro drug release, transcorneal drug permeation as well as DRC exhibited a proportional increase with increasing drug loading in the ointment. On comparing the in vitro drug release profile with transcorneal permeation profile, it appears that drug release from the ointment is controlling acyclovir transport through the cornea. Furthermore, enhanced in vitro transcorneal permeation relative to the in vitro drug release underscores the importance of the interplay between the physiology of the ocular tissue and ointment formulation. The results indicated that IVRT and IVPT could be used to discriminate the impact of changes in drug load and formulation composition of ophthalmic ointments.
Food and Drug Administration, CDER/OPQ/OTR/DPQR, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Manar
M
Al-Ghabeish
Food and Drug Administration, CDER/OPQ/OTR/DPQR, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Xiaoming
X
Xu
Food and Drug Administration, CDER/OPQ/OTR/DPQR, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Yellela S R
YS
Krishnaiah
Food and Drug Administration, CDER/OPQ/OTR/DPQR, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Ziyaur
Z
Rahman
Food and Drug Administration, CDER/OPQ/OTR/DPQR, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Yang
Y
Yang
Food and Drug Administration, CDER/OPQ/OTR/DPQR, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Electronic address: Mansoor.Khan@fda.hhs.gov.
Mansoor A
MA
Khan
D000212:Acyclovir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D060433:Administration, Ophthalmic; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003315:Cornea / Q000378:metabolism*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D008297:Male; D009824:Ointments; D010539:Permeability; D011817:Rabbits
D000998:Antiviral Agents; D009824:Ointments; D000212:Acyclovir
Acyclovir; Drug release; Drug retention in cornea; Ophthalmic ointment; Performance tests; Semisolid dosage form; Transcorneal permeation