ABSTRACT
The nonpolar parameter of solid surface free energy gamma(s)(d) has been determined for some pharmaceutical powders by means of contact angle measurement (Wilhelmy plate method) and inverse phase gas chromatography (IGC). For most samples, a good correlation between the results of the two methods was found. Additionally it was found that to get comparable results with the IGC method, contact angles obtained with totally nonpolar liquid should be used for calculating gamma(s)(d). Comparison of our results with those from the literature showed that the correlation depends on the method used for contact angle determination and the properties of the liquids used for contact angle measurements.
Subject(s)
Chromatography, Gas/methods , Technology, Pharmaceutical , PowdersABSTRACT
The glassy state of felodipine was prepared by melting crystals of felodipine on a clean glass slide and cooling to room temperature. It has been confirmed that glassy felodipine is a metastable state, and undergoes transformation to the more stable crystalline form. Crystallization occurred slowly and spontaneously at room temperature, below the glassy state transition temperature (Tg). The contact mode of atomic force microscopy was used for topographical imaging of the glassy and crystalline states of felodipine. When the glassy felodipine region next to the recrystallized zone was exposed to controlled mechanical stress through the tip, rapid additional crystallization was observed. This crystallization process can be induced and imaged in real time by atomic force microscopy.
Subject(s)
Calcium Channel Blockers/chemistry , Felodipine/chemistry , Microscopy, Atomic Force , CrystallizationABSTRACT
Surface free energy was determined for model substances pentoxyfilline, acyclovir, lactose and binding agents (that were used in the granulation process) hydroxypropilmethyl cellulose (HPMC) and polyvinylpyrrolidone (PVP) were determined by contact angle measurements. The methods of Wu, Good-van Oss and Della Volpe were used for solid-surface free-energy calculation. Spreading coefficients (S) were calculated and correlated with granulate properties. Granulates consisted of model drug and binding agent, and were produced in fluid bed granulator Glatt powder coater granulator GPCG1 by means of spraying the colloidal solution of binder on the model substance. Granules contained either 5% or 10% binder. Inverse granules, however, were also produced by spraying the model drug (i.e. pentoxyfilline and lactose) on the binding agent (HPMC, PVP). Particle size distribution, friability, true density, bulk density and tapped density of the granulates were determined. Although many different parameters influence the granule properties, it has been found that the interactions between the drug and the binder play a very important role. Spreading coefficients were found to be in good correlation with the friability of granulates. Positive spreading coefficient values of the binder over the model substance correlate well with the low friability of the granules containing lower amount of binder, i.e. 5%. In the group of the same binder, the spreading coefficient values decrease from pentoxyfilline over lactose to acyclovir. Friability results show that, for the system under consideration, PVP offers certain advantages over the grade of HPMC employed. The increase of the binder amount from 5 to 10% resulted in more friable granulates. Lower work of cohesion of the binder (PVP and HPMC) than the work of adhesion between binder and the model substances is considered responsible for the higher friability of the granules. The inverse granulation process, where the suspension of the model substance was sprayed over the solid binder particles, proved more efficient with HPMC than with PVP. According to the spreading coefficient results, the binder should spread over the drug. However, the kinetics of wetting appears to play an important role in the granulation process. According to these results, the conclusion was made that water wets HPMC much faster than PVP.
