Monitoring of multiple solvent induced form changes during high shear wet granulation and drying processes using online Raman spectroscopy.

Form changes during drug product processing can be a risk to the final product quality in terms of chemical stability and bioavailability. In this study, online Raman spectroscopy was used to monitor the form changes in real time during high shear wet granulation of Compound A, a highly soluble drug present at a high drug load in an extended release formulation. The effect of water content, temperature, wet massing time and drying technique on the degree of drug transformation were examined.

Determination of process variables affecting drug particle attrition withinmulti-component blends during powder feed transmission.

The aim of this study was to determine the location of attrition of formulated API particles within a powder feed system using a Morphologi G3-ID system, an image analyzer with integrated Raman capability enabling classification of particles with respect to their chemistry, to extract the API size distribution from the blended sample. The study also aimed to investigate the impact of other process variables, such as feed screw speed, on the extent of attrition observed. The study demonstrated that attrition occurs in two zones of the powder feed system, at the bottom of the hopper at the interface with the feed screw, and also within the feed screw itself.

Development of oral extended release formulations of 6-hydroxybuspirone.

Reducing the maximum plasma concentration whilst maintaining the exposure was shown to ameliorate adverse events following the oral administration of 6-hydroxybuspirone. This observation, along with a desire to provide for once daily dosing of this compound, provided the basis for the development of an extended release formulation. Hydrophilic matrix tablets based on hydroxypropyl methylcellulose and containing citric acid to provide for an acid microenvironment were prepared and evaluated by in vitro drug release studies and in vivo pharmacokinetic and scintigraphic studies using samarium oxide (¹⁵³Sm) labelled dosage forms.

Formulation and process design for a solid dosage form containing a spray-dried amorphous dispersion of ibipinabant.

Amorphous forms of poorly soluble drugs are more frequently being incorporated into solid dispersions for administration and extensive research has led to a reasonable understanding of how these dispersions, although still kinetically unstable, improve stability relative to the pure amorphous form. There remains however a paucity of literature describing the effects on such solid dispersions of subsequent processing into solid dosage forms such as tablets. This paper addresses this area by looking at the effects of the addition of common excipients and different manufacturing routes on the stability of a spray-dried dispersion (SDD) of the cannabinoid CB-1 antagonist, ibipinabant.

Roller compaction: application of an in-gap ribbon porosity calculation for the optimization of downstream granule flow and compactability characteristics.

This paper reports the use of an in-gap ribbon porosity calculation for the optimisation of roller compaction ribbon parameters in order to control downstream granule and tablet properties for a typical pharmaceutical formulation. The study demonstrates the effect of changes to roll speed and roll gap on the relative level of ribbon compaction for ribbons with equivalent in-gap porosities. It is demonstrated that in-gap ribbon porosity can be applied to enable optimization of the downstream granule processability characteristics for a typical pharmaceutical formulation and an understanding of the control space of a roller compaction process.

Roller compaction: Application of an in-gap ribbon porosity calculation for the optimization of downstream granule flow and compactability characteristics.

This paper reports the use of an in-gap ribbon porosity calculation for the optimisation of roller compaction ribbon parameters in order to control downstream granule and tablet properties for a typical pharmaceutical formulation. The study demonstrates the effect of changes to roll speed and roll gap on the relative level of ribbon compaction for ribbons with equivalent in-gap porosities. It is demonstrated that in-gap ribbon porosity can be applied to enable optimization of the downstream granule processability characteristics for a typical pharmaceutical formulation and an understanding of the control space of a roller compaction process.

Amorphous drug-PVP dispersions: application of theoretical, thermal and spectroscopic analytical techniques to the study of a molecule with intermolecular bonds in both the crystalline and pure amorphous state.

We report the case of BMS-488043-PVP solid dispersions which when analysed using modulated DSC showed compliance with the Gordon-Taylor model, confirming ideal mixing behaviour of the two components. The nature or presence of stabilising interactions between drug and PVP could not be confirmed using this technique. Use of FT-IR, Raman and solid-state NMR spectroscopy confirmed the presence of stabilising hydrogen bond interactions between the drug and PVP.

Monitoring and end-point prediction of a small scale wet granulation process using acoustic emission.

A study to establish if acoustic emission could be used to monitor a small scale (120 g batch size) high shear granulation process and predict the process end-point, is reported. The robustness of the prediction model was further assessed by changing process variables. It is demonstrated that the technique is capable of repeatedly producing granules with consistent physical characteristics, such as particle size distribution and bulk density, despite changes in batch size and liquid dose rates.