Perspectives on Physicochemical and In Vitro Profiling of Ophthalmic Ointments

Abstract

Ophthalmic ointments are unique in that they combine features of topical drug delivery, the ophthalmic route and ointment (semisolid) formulations. Accordingly, these complex formulations are challenging to develop and evaluate and therefore it is critically important to understand their physicochemical properties as well as their in vitro drug release characteristics. Previous reports on the characterization of ophthalmic ointments are very limited. Although there are FDA guidance documents and USP monographs covering some aspects of semisolid formulations, there are no FDA guidance documents nor any USP monographs for ophthalmic ointments. This review summarizes the physicochemical and in vitro profiling methods that have been previously reported for ophthalmic ointments. Specifically, insight is provided into physicochemical characterization (rheological parameters, drug content and content uniformity, and particle size of the API in the finished ointments) as well as important considerations (membranes, release media, method comparison, release kinetics and discriminatory ability) in in vitro drug release testing (IVRT) method development for ophthalmic ointments.

Influence of Concentration on Release and Permeation Process of Model Peptide Substance-Corticotropin-From Semisolid Formulations

“…The three most commonly used models (zero-order, logarithmic and Higuchi) were used to investigate the kinetics of the release of loteprednol ethabonate from ointments based on lipophilic base (white petroleum jelly and mineral oil 69.2%:30.3% ( w / w )). The value of the fitting factor (R 2 ) between the three models showed the following order: Higuchi (more suited for lipophilic ointments) > logarithmic > zero order [ 56 , 57 ].…”

“…The three most commonly used models (zero-order, logarithmic and Higuchi) were used to investigate the kinetics of the release of loteprednol ethabonate from ointments based on lipophilic base (white petroleum jelly and mineral oil 69.2%:30.3% (w/w)). The value of the fitting factor (R 2 ) between the three models showed the following order: Higuchi (more suited for lipophilic ointments) > logarithmic > zero order [56,57]. Olejnik et al in studies of undecylenoyl phenylalanine (Ude-Phe) release from the formulation for skin application (studies of Ude-Phe from topical formulations), depending on the membrane used, described the results with different models: For Cuprophan membrane the Higuchi model was used, for cellulose acetate and nitrocellulose membranes the Korsmeyer-Peppas model, while for Strat-M membrane the highest correlation coefficient was observed for reaction models "0" and "I" of the order.…”

“…Rheological properties of ointments have a great significance during production process (e.g., filling of tubes, pumping through tubes, and storage), application from the container to the administration place (the ointment should not be too thick or too thin) and aesthetics. In addition, rheological properties are critical to understand the microstructure of ointment formulations [56,66,67].…”

Pre-Formulation Studies: Physicochemical Characteristics and In Vitro Release Kinetics of Insulin from Selected Hydrogels

“…We found no relationship between the viscosity of the analyzed preparations and the amount of insulin release/diffusion rate from the analyzed formulations. Literature data confirm that semi-solid preparations of high viscosity can show both high and low diffusion rates compared to semi-solid preparations of lower viscosity [77]. One of the important problems of topical insulin administration is its short half-life (3-5 min in the blood) and the loss of bioactivity due to the presence of peptidases in the wound environment [78,79].…”

Refining the rheological characteristics of high drug loading ointment via SDS and machine learning

“…The ointment should have enough yield stress to prevent it from flowing out of the container when placed at random [ 41 – 43 ]. At the same time, it should not be too large, otherwise the ointment will not be easy to spread on the skin during use [ 44 , 45 ]. The yield stress values were determined by the variation in the stored energy modulus during strain scans ( Fig 1A ).…”