Quantifying the Degree of Disorder in Micronized Salbutamol Sulfate Using Moisture Sorption Analysis

Abstract

Salbutamol sulfate is often micronized for use in dry powder inhalers. Therefore, it is of high interest to quantify the amorphous amount. It was investigated whether moisture sorption is able to measure the amorphous content of salbutamol sulfate. Different mixtures of amorphous and crystalline salbutamol sulfate were analyzed by moisture sorption. The amorphous material was obtained by spray drying. The measurement results were used to plot a calibration curve, which was used to quantify the amorphous amount in micronized salbutamol sulfate.

Influence of micronization on the physical properties of salbutamol sulfate as a model drug used in dry powder inhalation

“…The corresponding sorption data are shown in Figure 4b. [11] In contrast to crystalline salbutamol sulfate, there is a mass decrease observable at 50% RH and above. The calculation of the amorphous content showed that the micronized salbutamol sulfate contains 1.65% amorphous material.…”

“…The micronized salbutamol sulfate samples conditioned for 24 h at 52.8% RH and 75% RH still show amorphous parts [Figure 4c and d, respectively] indicating that recrystallization has not been completed yet. Using the calculating method mentioned by Gorny et al, 2007, it has been found that the amorphous content of salbutamol sulfate stored at 52.8% and 75% relative humidity is 0.35% and 0.29%, respectively.…”

“…[7] Hence, the detection limits for amorphous content with such techniques will generally have a lower cut off of 5%-10%. [10] Very few techniques such as isothermal microcalorimetry (IMC) [11,12] and dynamic vapor sorption (DVS) [13] are capable of quantifying very low levels of amorphous content. Selection of experimental conditions and the mathematical treatment of the data made the use of techniques, such as IMC more complex.…”

Carrier-based dry powder inhalation: Impact of carrier modification on capsule filling processability and in vitro aerodynamic performance

“…The authors are well aware that SS is completely amorphous after spray drying (see the WAXS pattern of the amorphous SS in the Supplementary part) and recrystallizes at 60% RH and 25 C room temperature (Gorny et al, 2007;Littringer et al, 2013c). Therefore, all samples were prepared under same (lower) temperature and humidity conditions and at the same day and it is unlikely that he observed phenomenon is originating from the environmental conditions.…”

Crystallization speed of salbutamol as a function of relative humidity and temperature

“…Spray drying did not alter salbutamol sulphate chemically but reduced the crystallinity of the resulting drug particles (Chawla et al, 1994). Further, Gorny et al and Littringer et al reported that spray drying of salbutamol sulphate from aqueous solutions results in amorphous particles (Gorny et al, 2007;Littringer et al, 2013). The challenge when working with amorphous products is the stability of the products as there is always the risk of recrystallization to the more stable crystalline state.…”