Biofilm formation by coagulase-negative staphylococci: impact on the efficacy of antimicrobials and disinfectants commonly used on dairy farms.

Coagulase-negative staphylococci (CNS) have traditionally been considered minor mastitis pathogens and are the bacteria most frequently isolated from intramammary infection. Previously, our laboratory demonstrated that a majority of CNS isolated from Canadian milk were able to form biofilm and this was strongly and positively associated with days in milk. Biofilms offer protection against antibiotics and disinfectants, and the presence of CNS biofilms near the end of the lactation cycle could have an impact on the prevention and recurrence of CNS infections in the next lactation cycle.

Using Flory-Huggins phase diagrams as a pre-formulation tool for the production of amorphous solid dispersions: a comparison between hot-melt extrusion and spray drying.

Objectives: Amorphous drug forms provide a useful method of enhancing the dissolution performance of poorly water-soluble drugs; however, they are inherently unstable. In this article, we have used Flory-Huggins theory to predict drug solubility and miscibility in polymer candidates, and used this information to compare spray drying and melt extrusion as processes to manufacture solid dispersions.

Method: Solid dispersions were prepared using two different techniques (hot-melt extrusion and spray drying), and characterised using a combination of thermal (thermogravimetric analysis and differential scanning calorimetry), spectroscopic (Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction methods.

Bulk, surface properties and water uptake mechanisms of salt/acid amorphous composite systems.

Developing amorphous pharmaceuticals can be desirable due to advantageous biopharmaceutical properties. Low glass transition temperature (Tg) amorphous drugs can be protected from crystallisation by mixing with high Tg excipients, such as polymers, or with salt forms. However, both polymers and salts can enhance the water uptake.

Amorphous solid dispersions of sulfonamide/Soluplus® and sulfonamide/PVP prepared by ball milling.

The aim of this paper is to investigate the physicochemical properties of binary amorphous dispersions of poorly soluble sulfonamide/polymeric excipient prepared by ball milling. The sulfonamides selected were sulfathiazole (STZ), sulfadimidine (SDM), sulfamerazine (SMZ) and sulfadiazine (SDZ). The excipients were polyvinylpyrrolidone (PVP) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer, commercially known as Soluplus®.

Investigation of the capacity of low glass transition temperature excipients to minimize amorphization of sulfadimidine on comilling.

The coprocessing of active pharmaceutical ingredient (API) with an excipient which has a high glass transition temperature (T(g)) is a recognized strategy to stabilize the amorphous form of a drug. This work investigates whether coprocessing a model API, sulfadimidine (SDM) with a series of low T(g) excipients, prevents or reduces amorphization of the crystalline drug. It was hypothesized that these excipients could exert a T(g) lowering effect, resulting in composite T(g) values lower than that of the API alone and promote crystallization of the drug.

Formation, physical stability, and quantification of process-induced disorder in cryomilled samples of a model polymorphic drug.

The formation and physical stability of amorphous sulfathiazole obtained from polymorphic forms I and III by cryomilling was investigated by X-ray powder diffraction (XRPD) and near-infrared (NIR) spectroscopy. Principal component analysis was applied to the NIR data to monitor the generation of crystalline disorder with milling time and to study subsequent recrystallization under different storage conditions. Complete conversion into the amorphous phase was observed for both forms after 45 (form I) and 150 min (form III) milling time.

Modification of the solid-state nature of sulfathiazole and sulfathiazole sodium by spray drying.

Solid-state characterisation of a drug following pharmaceutical processing and upon storage is fundamental to successful dosage form development. The aim of the study was to investigate the effects of using different solvents, feed concentrations and spray drier configuration on the solid-state nature of the highly polymorphic model drug, sulfathiazole (ST) and its sodium salt (STNa). The drugs were spray-dried from ethanol, acetone and mixtures of these organic solvents with water.

Solid state amorphization kinetic of alpha lactose upon mechanical milling.

It has been previously reported that α-lactose could be totally amorphized by ball milling. In this paper we report a detailed investigation of the structural and microstructural changes by which this solid state amorphization takes place. The investigations have been performed by Powder X-ray Diffraction, Solid State Nuclear Magnetic Resonance ((13)C CP-MAS) and Differential Scanning Calorimetry.

A comparison of spray drying and milling in the production of amorphous dispersions of sulfathiazole/polyvinylpyrrolidone and sulfadimidine/polyvinylpyrrolidone.

Formulations containing amorphous active pharmaceutical ingredients (APIs) present great potential to overcome problems of limited bioavailability of poorly soluble APIs. In this paper, we directly compare for the first time spray drying and milling as methods to produce amorphous dispersions for two binary systems (poorly soluble API)/excipient: sulfathiazole (STZ)/polyvinylpyrrolidone (PVP) and sulfadimidine (SDM)/PVP. The coprocessed mixtures were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and intrinsic dissolution tests.

Prediction of onset of crystallization in amorphous pharmaceutical systems: phenobarbital, nifedipine/PVP, and phenobarbital/PVP.

The aim of this work is to determine if a stability testing protocol based on the correlations between crystallization onset and relaxation time above the glass transition temperature (T(g)) can be used to predict the crystallization onsets in amorphous pharmaceutical systems well below their T(g). This procedure assumes that the coupling between crystallization onset and molecular mobility is the same above and below T(g). The stability testing protocol has been applied to phenobarbital, phenobarbital/polyvinylpyrrolidone (PVP) (95/5, w/w), and nifedipine/PVP (95/5, w/w).

Structure determination of the 1/1 alpha/beta mixed lactose by X-ray powder diffraction.

The mixed form of alpha/beta lactose was obtained by heating amorphous alpha-lactose at 443 K. NMR spectroscopy determined the stoichiometry of this mixed compound to be 1/1. The X-ray powder diffraction pattern was recorded at room temperature with a sensitive curved detector (CPS 120).