Characterization and physical stability of spray dried solid dispersions of probucol and PVP-K30.

The main purpose of this study was to obtain stable, well-characterized solid dispersions (SDs) of amorphous probucol and polyvinylpyrrolidone K-30 (PVP-K30) with improved dissolution rates. A secondary aim was to investigate the flow-through dissolution method for in-vitro dissolution measurements of small-sized amorphous powders dispersed in a hydrophilic polymer. SDs were prepared by spray drying solutions of probucol and different amounts of PVP-K30. The obtained SDs were characterized by dissolution rate measurements in a flow-through apparatus, X-ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), particle sizing (laser diffraction) and Brunauer-Emmett-Teller Method (BET) and results were compared with starting material and a physical mixture. The physical stability was monitored after storage at 25 degrees C and 60% RH for up to 12 weeks. The flow-through method was found suitable as dissolution method. All SDs showed improved in-vitro dissolution rates when compared to starting material and physical mixtures. The greatest improvement in the in-vitro dissolution rate was observed for the highest polymer to drug ratio. By means of the results from XRPD and DSC, it was argued that the presence of amorphous probucol improved the dissolution rate, but the amorphous state could not fully account for the difference in dissolution profiles between the SDs. It was suggested that the increase in surface area due to the reduction in particle size contributed to an increased dissolution rate as well as the presence of PVP-K30 by preventing aggregation and drug re-crystallization and by improving wettability during dissolution. The stabilizing effect of the polymer was verified in the solid state, as all the SDs retained probucol in the amorphous state throughout the entire length of the stability study.

Droplet size measurements for spray dryer scale-up.

This study was dedicated to facilitate scale-up in spray drying from an atomization standpoint. The purpose was to investigate differences in operating conditions between a pilot and a production scale nozzle. The intension was to identify the operating ranges in which the two nozzles produced similar droplet size distributions. Furthermore, method optimization and validation were also covered. Externally mixing two-fluid nozzles of similar designs were used in this study. Both nozzles are typically used in commercially available spray dryers, and they have been characterized with respect to droplet size distributions as a function of liquid type, liquid flow rate, atomization gas flow rate, liquid orifice diameter, and atomization gas orifice diameter. All droplet size measurements were carried out by using the Malvern Spraytec with nozzle operating conditions corresponding to typical settings for spray drying. This gave droplets with Sauter Mean Diameters less than 40 microm and typically 5-20 microm. A model previously proposed by Mansour and Chigier was used to correlate the droplet size to the operating parameters. It was possible to make a correlation for water incorporating the droplet sizes for both the pilot scale and the production scale nozzle. However, a single correlation was not able to account properly for the physical properties of the liquid to be atomized. Therefore, the droplet size distributions of ethanol could not be adequately predicted on the basis of the water data. This study has shown that it was possible to scale up from a pilot to production scale nozzle in a systematic fashion. However, a prerequisite was that the nozzles were geometrically similar. When externally mixing two-fluid nozzles are used as atomizers, the results obtained from this study could be a useful guideline for selecting appropriate operating conditions when scaling up the spray-drying process.

Scaling up the spray drying process from pilot to production scale using an atomized droplet size criterion.

PURPOSE: The purpose of this study was to investigate the possibility of producing identical powders in pilot and production scale spray drying equipment by matching the droplet size distributions produced by two differently sized atomizers. METHODS: Particles were prepared by spray drying solutions of acetaminophen and polyvinylpyrrolidone K-30. The success of the up-scaling was evaluated by comparing the powders in terms of particle size distribution (laser diffraction), crystallinity (XPRD) and morphology (SEM). Furthermore, the influence of process parameters on other product characteristics such as stability and residual volatile content was also evaluated. RESULTS: The spray drying experiments resulted in spherical, amorphous particles with volumetric median diameters of typically 4-10 microm for pilot scale and 4-30 microm for production scale. The results showed that particles with similar morphology and crystallinity could be produced in the two applied spray dryers. However, scale-up based purely on matching droplet size distributions was not feasible. CONCLUSIONS: The scale-up criterion did not account for the differences between the droplet-drying gas mixing and residence time distribution within the two spray dryers. Therefore, production scale experiments are required in order to obtain similar product characteristics as in pilot scale.

Characterization and physical stability of tolfenamic acid-PVP K30 solid dispersions.

Obtaining a stable formulation with high bioavailability of a poorly water-soluble drug often presents a challenge to the formulation scientist. Transformation of the drug into its more soluble high-energy amorphous form is one method used for improving the dissolution rate of such compounds. The present study uses the spray-drying technique for preparation of solid dispersions (SDs) of tolfenamic acid (TA) and polyvinylpyrrolidone K-30 (PVP). The SDs and TA in the form of a spray-dried powder were initially characterized and compared with a physical mixture and starting materials. Stability of the SDs was monitored over 12 weeks at 25 degrees C and 60% RH. XRPD studies revealed changes in solid state during the formation of the SDs and indicated the presence of TA in the amorphous state. FTIR, together with TGA, suggested molecular interactions (hydrogen-bonding) in the SDs. Dissolution studies proved an increase in the dissolution rate of TA from all SDs. The SDs with higher content of PVP retained TA in the amorphous state throughout the stability study. However, SDs with lower content showed recrystallization of TA after 1 week. Thus, this study reveals the possibility of preparing stable SDs of amorphous TA in PVP with improved dissolution rate.