Faiza Laredj

Background/Objectives: Minzasolmin is a weakly basic drug developed as a potential therapy in Parkinson’s. Amongst the strategies that have been developed to enhance API solubility, pH modification is an effective and patient-centric approach that improves solubility by creating a microenvironmental pH around the drug. The objective of this study was to evaluate different formulation approaches to develop an immediate-release tablet or capsule containing fumaric acid as a pH modifier. Methods: Ten formulations were developed, varying the degree of contact between the API and pH modifier. These formulations were then assessed in three biorelevant dissolution conditions to estimate their robustness towards variations in gastric pH. Results: In highly buffered conditions, only the over-encapsulated tablet showed a clear improvement in the dissolution profile, with up to 5.1 times the percentage dissolved compared to the capsule without acid and up to 1.4 times compared to the target granule-in-capsule with acid. In low-buffered conditions, though, all prototypes with acid showed an improvement in the percentage dissolved, between 54 and 79 times compared to that of the capsule without acid, regardless of the degree of contact between the organic acid and the API. This was associated with a decrease in pH to 5 in the gastric compartment. Conclusions: These results suggested that the acidic microenvironment, estimated via the bulk pH, and hence the dissolution rate may not require such a high degree of contact between the API and the pH modifier. Based on in vitro results, the over-encapsulated tablet as well as prototypes with a lower degree of contact between the acid and PI will be evaluated in vivo in a future study to evaluate the bio-relevance of the approach.

Background/Objectives: Minzasolmin is a weakly basic drug developed as a potential therapy in Parkinson’s. Amongst the strategies that have been developed to enhance API solubility, pH modification is an effective and patient-centric one that improves solubility by creating a microenvironmental pH around the drug. The objective of this study was to evaluate different formulation approaches to develop an immediate-release tablet or capsule containing fumaric acid as pH-modifier. Methods: Ten formulations were developed varying the degree of contact between the API and pH-modifier. These formulations were then tested in three Biorelevant dissolution conditions to estimate their robustness towards variations in gastric pH. Results: In vitro data showed the best dissolution rate with the over-encapsulated tablet prototype, even in highly buffered achlorhydric conditions and was therefore the most robust formulation toward elevated gastric pH. However, in low buffered achlorhydric conditions the monolayer tablet with acid exhibited similar dissolution rate and prototypes with less close contact between the API and the organic acid also demonstrated improved dissolution rates. Conclusions: These results suggested that the acidic microenvironment may not require such a high degree of contact between the API and the pH-modifier. Selected prototypes will be evaluated in vivo in a future study to evaluate the bio-relevance of the approach.