Patient-specific in vitro drug release testing coupled with in silico PBPK modeling to forecast the in vivo performance of oral extended-release levodopa formulations in Parkinson's disease patients.

Biorelevant in vitro release models are valuable analytical tools for oral drug development but often tailored to gastrointestinal conditions in 'average' healthy adults. However, predicting in vivo performance in individual patients whose gastrointestinal conditions do not match those of healthy adults would be of great value for optimizing oral drug therapy for such patients. This study focused on establishing patient-specific in vitro and in silico models to predict the in vivo performance of levodopa extended-release products in Parkinson's disease patients.

Review of paediatric gastrointestinal physiology relevant to the absorption of orally administered medicines.

Despite much progress in regulations to improve paediatric drug development, there remains a significant need to develop better medications for children. For the design of oral dosage forms, a detailed understanding of the specific gastrointestinal (GI) conditions in children of different age categories and how they differ from GI conditions in adults is essential. Several review articles have been published addressing the ontogeny of GI characteristics, including luminal conditions in the GI tract of children.

A Biopredictive In Vitro Approach for Assessing Compatibility of a Novel Pediatric Hydrocortisone Drug Product within Common Pediatric Dosing Vehicles.

Purpose: The objective of the present work was to screen whether a novel pediatric hydrocortisone granule formulation can be co-administered with common food matrices and liquids.

Methods: Pediatric hydrocortisone granules were studied using a biopredictive in vitro approach. Experiments included an in situ chemical compatibility study of active ingredient and drug product with liquid dosing vehicles and soft foods commonly ingested by infants, pre-school- and school children.

Biorelevant in vitro assessment of dissolution and compatibility properties of a novel paediatric hydrocortisone drug product following exposure of the drug product to child-appropriate administration fluids.

Alkindi® is a novel oral multi-particulate taste-masked formulation of hydrocortisone for use in children with the rare disease adrenal insufficiency. The objective of the present work was to study the biorelevant dissolution and compatibility properties of Alkindi® granules following exposure to administration fluids including breast milk, artificial milk, whole milk and water. To provide in vitro data for a representative patient collective, dosing conditions in neonates, infants and pre-school children were assessed.

A review of patient-specific gastrointestinal parameters as a platform for developing in vitro models for predicting the in vivo performance of oral dosage forms in patients with Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease that presents with visible motor symptoms, but that is accompanied by several additional symptoms, including gastrointestinal symptoms that may affect pharmacokinetics of oral medications. A detailed understanding of the nature of PD-specific gastrointestinal parameters and of how they may affect drug release of orally administered dosage forms seems to be essential information for developing better oral PD medications. The availability of bio-predictive drug release models simulating PD-specific gastrointestinal parameters would also be beneficial for this purpose.

Development and Validation of a Robust and Efficient HPLC Method for the Simultaneous Quantification of Levodopa, Carbidopa, Benserazide and Entacapone in Complex Matrices.

Purpose: A variety of fixed-dose combination products is used in the therapy of Parkinson Disease. However, to date a proper analytical method applicable for comparative screening of different antiparkinson products was not available. The objective of the present work was thus to develop and validate an analytical method for the simultaneous quantification of levodopa, carbidopa, benserazide and entacapone.