Solvent influences on metastable polymorph lifetimes: real-time interconversions using energy dispersive X-ray diffractometry.

Solvent influences on the crystallization of polymorph and hydrate forms of the nootropic drug piracetam (2-oxo-pyrrolidineacetamide) were investigated from water, methanol, 2-propanol, isobutanol, and nitromethane. Crystal growth profiles of piracetam polymorphs were constructed using time-resolved diffraction snapshots collected for each solvent system. Measurements were performed by in situ energy dispersive X-ray diffraction recorded in Station 16.

Modulation of drug release kinetics from hydroxypropyl methyl cellulose matrix tablets using polyvinyl pyrrolidone.

Hydrophilic matrix tablets are widely used to extend the release of a broad range of pharmaceutically active materials. The mechanism and kinetics of drug release are dependent on the solubility of the active moiety and the swelling and erosion properties of the polymer, with water soluble compounds released predominantly by diffusion. The swelling and erosion properties of hydroxypropyl methyl cellulose (HPMC), typically lead to a first order release rate for water soluble compounds as opposed to the more desirable zero-order kinetics.

The development of a stable, coated pellet formulation of a water-sensitive drug, a case study: development of a stable core formulation.

A development program has been carried out to provide a stable extrusion/spheronisation pellet formulation for a highly water-soluble drug, sitagliptin, which undergoes a change in physical form on processing and is subject to hydrolytic decomposition. A conventional extrusion/spheronization formulation resulted in significant degradation of the drug. The inclusion of glyceryl monostearate into the formulation was found to reduce the water levels required to such a level that there was no significant degradation of the drug during processing to form pellets.

Evaluation of drug physical form during granulation, tabletting and storage.

An active pharmaceutical ingredient (API) was found to dissociate from the highly crystalline hydrochloride form to the amorphous free base form, with consequent alterations to tablet properties. Here, a wet granulation manufacturing process has been investigated using in situ Fourier transform (FT)-Raman spectroscopic analyses of granules and tablets prepared with different granulating fluids and under different manufacturing conditions. Dosage form stability under a range of storage stresses was also investigated.

Rational design of powder formulations for tamp filling processes.

Tamp filling processes are widely used for the filling of powders into hard gelatin capsules, whereby capsule fill weight is controlled by the formation of a loosely packed plug of material that is dispensed into the capsule shell. To rationally design formulations for tamp filling processes the formulator must have an intimate knowledge of the synergy between machine parameters and powder properties and the corresponding effect on product quality. However, despite ubiquitous use throughout the pharmaceutical industry, relatively little is understood about the design of powders for tamp filling processes.

Effect of moisture on polyvinylpyrrolidone in accelerated stability testing.

Accelerated stability studies are a common approach for predicting the long-term stability of pharmaceutical formulations. However, in this study, a slowing of dissolution was observed for a formulation following storage at elevated temperature and humidity. The moisture sorption isotherm for the binder, polyvinylpyrrolidone (PVP), shows absorption of a significant quantity of water on exposure to elevated humidity.

Quantitative analysis of mannitol polymorphs. X-ray powder diffractometry--exploring preferred orientation effects.

Mannitol is a polymorphic parmaceutical excipient, which commonly exists in three forms: alpha, beta and delta. Each polymorph has a needle-like morphology, which can give preferred orientation effects when analysed by X-ray powder diffractometry (XRPD) thus providing difficulties for quantitative XRPD assessments. The occurrence of preferred orientation may be demonstrated by sample rotation and the consequent effects on X-ray data can be minimised by reducing the particle size.

Quantitative analysis of mannitol polymorphs. FT-Raman spectroscopy.

Mannitol is a polymorphic excipient which is usually used in pharmaceutical products as the beta form, although other polymorphs (alpha and delta) are common contaminants. Binary mixtures containing beta and delta mannitol were prepared to quantify the concentration of the beta form using FT-Raman spectroscopy. Spectral regions characteristic of each form were selected and peak intensity ratios of beta peaks to delta peaks were calculated.