A biopharmaceutical classification-based Right-First-Time formulation approach to reduce human pharmacokinetic variability and project cycle time from First-In-Human to clinical Proof-Of-Concept.

A Right-First-Time approach is described for developing bona fide formulations for First-In-Human (FIH) to Proof-Of-Concept (POC) studies to meet an overarching goal of reduced project cycle time from IND to NDA (as short as four years). Bona fide formulations are tailor-made according to the drug's biopharmaceutical properties including solubility, permeability and stability. Solubilization techniques are used extensively to reduce oral absorption variability for most compounds.

Performance qualification of a new hypromellose capsule: part I. Comparative evaluation of physical, mechanical and processability quality attributes of Vcaps Plus, Quali-V and gelatin capsules.

This Part I paper describes the qualification of a new high performance hypromellose (hydroxypropyl methylcellulose, HPMC) capsule shell which contains no gelling agent and is dissolution friendly. The development history and the test results for a series of quality attributes including scanning electron microscopy, hygroscopicity, machineability, weight variation, powder leakage, mechanical strength, stability, cross-linking, animal and human pharmacokinetic results are reported. Comparisons to gelatin and HPMC capsule containing carrageenan showed the new HPMC capsule is superior in terms of mechanical strength, hygroscopicity and compatibility with a wide range of drugs.

Evaluation of abdominal wall strength after TRAM flap surgery.

Evaluation of abdominal wall function after transverse rectus abdominis musculocutaneous (TRAM) flap surgery has been mostly subjective. The purpose of this study was to measure abdominal wall strength objectively and to compare the results with the patient's performance of daily activities. Abdominal wall strength was objectively measured with the B200 IsoStation machine preoperatively and 1 year after TRAM flap breast reconstruction.

A comparison of the effects of streptozotocin, N-methylnitrosourea and alloxan on isolated islets of Langerhans.

Isolated normal rat islets were pre-incubated with Streptozotocin (STZ), N-methylnitrosourea (MNU) or alloxan for 5, 10, 30 or 60 minutes at 0 degree C or 37 degrees C, and then were washed and incubated at 37 degrees C for 60 minutes with glucose (16.7 mM). Suppression of the insulinotropic response to glucose during incubation required 10 minutes of pre-incubation with the nitrosoureas whose effects were directly related to concentration and were temperature dependent.

The characterization of phenazine methosulfate stimulated insulin secretion.

This investigation was initiated to characterize the stimulation of insulin secretion by phenazine methosulfate (PMS). Islets of Langerhans, isolated by the collagenase method from normal rats and rats pre-injected with either streptozotocin or 6-aminonicotinamide, were exposed to PMS under various experimental conditions and insulin secretion in response to PMS, glucose and pyridine nucleotides was determined. Insulin releasing action of PMS was dose-, time- and temperature-related, occurred in the absence of glucose, and was inhibited by epinephrine, but not by mannoheptulose.