Challenges of developing in vitro release methods for petrolatum-based ointment formulations

Posted September 1, 2016

The testing of semisolids and topical dermatological drug products using in vitro release testing (IVRT) is becoming an official requirement for pharmaceutical industries to determine drug availability and to ensure batch-to-batch uniformity.

The test has been found to be valuable in evaluating the equivalence of a product after scale-up and post-approval changes, and for changes in a site of manufacture or cross-product/manufacturer comparison.

Ointments are therapeutically effective and, therefore, there are large varieties of these topical products currently available in the North American market. Consequently, there is high demand for developing a reproducible and sensitive IVRT methodology that can be used for product performance, quality control or SUPAC-specified changes.

However, the development of a vitro release testing methodology for petrolatum-based ointments presents considerable difficulties due to the low polarity of these ointments and the slow diffusion of active ingredients from their highly lipophilic matrixes.

For ointment products containing water-insoluble drugs, the challenge has been to find an appropriate synthetic membrane and a receptor media which allows drug release at measurable levels and maintains sink conditions during in vitro studies.

In many cases the amounts of analytes reaching the receptor are below the detection limit of the analytical procedures, especially during the initial sampling time periods. Indeed, release of drugs from petrolatum bases into an aqueous receptor was reported as “almost nil." The relative error associated with these low concentrations is consequently large, rendering the in vitro release profile less reliable.

In some cases more than one analyte is present in ointments which can have different physical-chemical properties.  This further complicates the development of suitable IVRT methodologies.

At DiTEBA we have developed methodologies that successfully overcome these challenges and have accomplished the in vitro release methods for the assessment of drug release from topical petrolatum-based ointment formulations.

The results obtained indicate that the in vitro release methods that have been developed are able to detect the effects of changes in formulation in which drugs are suspended and/or dissolved.

It is evident, from the data obtained from these methods, that the in vitro release test procedures are simple, reliable, reproducible and discriminatory.


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