Michael Christopher Roy

Improved Protocol and Data Analysis for Accelerated Shelf-Life Estimation of Solid Dosage Forms

PurposeTo propose and test a new accelerated aging protocol for solid-state, small molecule pharmaceuticals which provides faster predictions for drug substance and drug product shelf-life.Materials and MethodsThe concept of an isoconversion paradigm, where times in different temperature and humidity-controlled stability chambers are set to provide a critical degradant level, is introduced for solid-state pharmaceuticals. Reliable estimates for temperature and relative humidity effects are handled using a humidity-corrected Arrhenius equation, where temperature and relative humidity are assumed to be orthogonal. Imprecision is incorporated into a Monte-Carlo simulation to propagate the variations inherent in the experiment. In early development phases, greater imprecision in predictions is tolerated to allow faster screening with reduced sampling. Early development data are then used to design appropriate test conditions for more reliable later stability estimations.ResultsExamples are reported showing that predicted shelf-life values for lower temperatures and different relative humidities are consistent with the measured shelf-life values at those conditions.ConclusionsThe new protocols and analyses provide accurate and precise shelf-life estimations in a reduced time from current state of the art.

Extrudable core system : Development of a single-layer osmotic controlled-release tablet

A new controlled-release, extrudable core system (ECS) tablet has been developed which osmotically delivers high doses of low solubility active pharmaceutical ingredients (APIs). The tablet has a single core formed in a modified oval shape with a semi-permeable coating. The core contains hydroxyethylcellulose, which serves to entrain the API particles as they are extruded out a hole in the coating at one end of the tablet, and a sugar, which provides the osmotic driving force for water imbibing. The dosage form has been successfully shown to control delivery of API over a range of delivery rates even with 50% of the tablet being API (up to about 500 mg).

Use of Oxygen Scavengers to Stabilize Solid Pharmaceutical Dosage Forms: A Case Study

A case study is described where degradation of a solid pharmaceutical dosage form susceptible to oxidation is minimized by incorporation of an oxygen scavenger as part of the packaging. Extremely low oxygen levels are attainable within 24 hr of packaging, even with permeable high-density polyethylene bottles commonly used in the pharmaceutical industry. This packaging methodology allows for a practical formulation-independent pathway for reducing or eliminating oxidative instability. In addition, this technology provides a convenient mechanistic probe for the degradation mechanism of solid dosage forms.