Title:Sensitive HPLC Method to Support Pre-formulation Studies and to Determine Critical Quality Attributes of Therapeutic Contact Lenses Containing Dorzolamide Hydrochloride
Volume: 20
Issue: 9
Author(s): Harshilkumar Jani, Ketan Ranch*, Rahul Lalwani, Yashkumar Patel, Kunjan Bodiwala and Anuradha Gajjar
Affiliation:
- Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy, Navrangpura, Ahmedabad,
380009, India
Keywords:
Dorzolamide hydrochloride, high performance liquid chromatography, therapeutic contact lenses, preformulation studies, nanoformulation, critical quality attributes.
Abstract:
Background: Dorzolamide hydrochloride (DRZ) is a carbonic anhydrase inhibitor used
to treat glaucoma and ocular hypertension. Drug-eluting contact lenses, such as Acuvue Theravision
™ with Ketotifen, offer improved drug delivery and reduced side effects compared to eye
drops. Drug-loaded nanoparticle-loaded contact lenses can sustain drug release and enhance comfort
for extended wear.
Objectives: High buffer concentration and low pH increase the risk of damage to silica-bonded
columns. Therapeutic contact lenses face challenges related to critical lens parameters, including
the estimation of drug incorporation and release due to interference of lens matrix leaching. There
is currently no analytical method available for estimating DRZ in contact lenses.
Methods: The HPLC method, which was developed and validated using ICH Q2 (R1) criteria,
used a C18 column (250 mm × 4.6 mm, 5 μm) as a stationary phase and methanol:water (70:30
v/v) as the mobile phase. The detecting wavelength was 253 nm. Moreover, to support the efficiency
of the developed method, the marketed formulation of DRZ eye drops, drug purity, and loading
in contact lenses were analysed. The method was also employed to determine the Critical Quality
Attributes (CQAs) of therapeutic contact lenses and drug release and drug leaching during the sterilization
process.
Results: The developed HPLC method shows Rt for DRZ at 2.881 minutes with good linearity (r2
> 0.998) between 2-32μg/mL, precision (RSD < 2%), accuracy (Recovery > 99.5%), sensitivity,
and specificity for quantifying DRZ in marketed formulations and therapeutic contact lenses. The
developed method is devoid of any buffer or modifier in the mobile phase, making it safer for the
stationary phase. This method mitigates the interference of lens matrix leaching, which induces an
overestimation of DRZ. All the result for therapeutic contact lenses was found to be closely
aligned with theoretically expected results, confirming the reliability of the developed HPLC
method for therapeutic contact lenses.
Conclusion: This method is specific, accurate, and precise for quantifying DRZ in commercial formulations
and newly developed therapeutic contact lenses. It effectively evaluates the critical quality
attributes of these lenses, demonstrating their reliability for assessing their performance and ensuring
quality in therapeutic applications.