Application/Technical Notes

 

FLUX


This technical note introduces devices that can be utilized for flux measurements in a systematic and reproducible manner. The small volume apparatus called μFLUX is compatible with Pion’s mini-bath (MB-8) and can be used on various stages of formulation development when amount of API and/or its formulations is limited while many permutations of different formulation strategies have to be investigated. The other device MacroFLUX is an absorption chamber insert into USP 1 or 2 dissolution bath vessels. Both apparati would allow assessment of complex interplay between solubility, permeability and dissolution rate in formulation development and would provide valuable tools for in vivo predictive in vitro studies.

 

PULSE™


The pKa determination by UV titration relies on the differences in molar absorptivity between charged and uncharged species present in solution[1]. The traditional UV titration of a compound takes about 25–30 minutes. The fast UV titration method utilizes Pion’s linear universal buffer Prisma™ HT. It enables replacing a variable volume titrant addition with a constant volume addition that produces predictable pH change with each dispensed aliquot of KOH or HCl. This technical note demonstrates that reducing the number of titration points while keeping their uniform distribution along pH axis produces comparable results to the regular UV titrations while reducing the assay time to 7–10 minutes per titration. Additional potential benefit of fast titrations is that low-soluble compounds can stay supersaturated for a short period of time. That may enable aqueous pKa measurements for some low-soluble compounds that otherwise have to be determined only with the presence of cosolvent. It can also benefit compounds that are not stable and would decompose during the long assay.

 

PAMPA


Applying transdermal patches to deliver active pharmaceutical ingredients (API) through the human skin provides numerous advantages compared to traditional dosage forms. Therefore, more and more efforts are devoted to the development of these formulations. To help the evolution of the patches, Skin PAMPA provides a unique opportunity to continuously estimate the performance of the patch during the early stages of development. This can help the formulator test various combinations, aiming to reach the most promising matrix for each API.

 

Studying the permeation properties of formulations is crucial in all stages of dermal and transdermal formulation development. Most of the available methods suffer from being labor-intensive and having poor reproducibility. Skin PAMPA technology is a useful tool for the early stages of development as it is an easy-to-use, cost-effective, and standardized model with significantly lower variation compared to most of the available methods. This technical note provides an example of studying three commercially available diclofenac formulations using Skin PAMPA model.

 

µDISS Profiler™


Nanoparticle formulations of active pharmaceutical ingredient (API) are often made in the form of a suspension with addition of surfactants to prevent nanoparticles from aggregating. The concentration of dissolved API in the nanosuspension is often unknown and determining the solubility of API when nanosuspension is added to the assay media is challenging. This technical note will describe the use of Zero Intercept Method (ZIM) implemented in Au PRO™ software to resolve these issues.

 

Because of its well characterized fluid hydrodynamics, the rotating disk method is a useful tool for mechanistic dissolution studies. The disk intrinsic dissolution rate (DIDR) measurements have been used to characterize solid drugs, including studies of dissolution-pH rate profiles in the presence of buffers, complexing agents, and various excipients. It is currently debated at the FDA whether the DIDR method can be used to determine solubility class membership in the Biopharmaceutics Classification System, with encouraging early indications.