Abstract
The formulation of active pharmaceutical ingredients (APIs) in amorphous solid dispersions (ASDs) is a promising approach to improve the bioavailability of poorly soluble compounds. However, problems often arise in the production of tablets from ASDs regarding the compressibility and recrystallization of the API. In the present study, the preparation of spray-dried ASDs of paracetamol (PCM) and four different types of polyvinylpyrrolidone (PVP) and their further processing into tablets were investigated. The influence of PVP type on the glass transition temperature (Tg) and the physical stability of ASD powders were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). ASD powders with 10 to 30% PCM were stable for at least 48 weeks. PCM contents of 40 to 50% led to recrystallization of the amorphous PCM within a few days or weeks. ASD with PVP/vinyl acetate (VA) copolymer (PVP/VA) was the most unstable and tended to recrystallize in PCM polymorphic form II. This formulation was therefore used for tablet studies. The influence of compression force on recrystallization, crushing strength, and drug release was investigated. Even high compression forces did not affect the stability of the ASD. However, the ASD tablets led to slow release of the API.
Highlights
The majority of new active pharmaceutical ingredients (APIs) have low water solubility
When polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone vinyl acetate (PVP/VA) are associated with low concentrations of API, the drug release is polymer-controlled; formulations with high concentrations of the API tend to result in a release rate similar to that of amorphous
The recrystallization behavior under different storage conditions was determined by X-ray diffraction (XRD)
Summary
The majority of new active pharmaceutical ingredients (APIs) have low water solubility. Amorphous solid dispersions (ASDs) are a common approach to improve solubility and bioavailability [1]. In ASDs, the API is molecularly dispersed in an amorphous carrier. The dissolution properties of the carrier are important for the release of the API and for the type of API and the drug to polymer ratio. When polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone vinyl acetate (PVP/VA) are associated with low concentrations of API, the drug release is polymer-controlled; formulations with high concentrations of the API tend to result in a release rate similar to that of amorphous. This property can lead to an improvement in the solubility and dissolution rate
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