Thermal analysis of amorphous lactose and $\alpha$-lactose monohydrate
ABSTRACT It is common to find that some of the lactose in dairy powders and pharmaceutical tablets is present in the unstable amorphous state. If stored at inappropriate temperatures and humidities amorphous lactose is susceptible to crystallization. The integration of thermal gravimetric analysis (TGA) with single differential thermal analysis (SDTA) provided a descriptive method for a sequential and direct determination of surface water, water of crystallization and amorphous lactose in a single analysis on one sample. Peaks and mass changes on the TGA/SDTA thermograms characteristic of surface water, water of crystallization and amorphous lactose were identified. The content of water of crystallization was used to estimate $\alpha$-lactose monohydrate. The loss of surface water was indicated on the TGA/SDTA thermograms as weight loss between 40 and 130 °C and the loss of water of crystallization occurred at 153 °C. Amorphous lactose was indicated by an exothermic crystallization peak at 174 °C. The area under the exothermic crystallization peak was linearly related to the proportion of the amorphous lactose in mixtures with $\alpha$-lactose monohydrate ($r = 0.989$). This work presented the TGA/SDTA thermograms of lactose samples containing some crystalline forms of lactose and amorphous lactose. The study compared the methods for determining surface water and total water content of lactose accepted by official bodies worldwide with the TGA/SDTA approach. The potential of new methods for qualitatively detecting the amorphous and crystalline forms of lactose by thermochemistry and Fourier transform infra-red (FT-IR) was also explored and compared. Généralement une partie du lactose dans les poudres laitières et les comprimés pharmaceutiques se trouve à l'état amorphe instable. S'il est conservé à des températures et humidités inappropriées, le lactose amorphe peut cristalliser. Le couplage de l'analyse thermogravimétrique (TGA) avec l'analyse thermique différentielle (SDTA) a fourni une méthode descriptive pour la détermination séquentielle et directe de l'eau de surface, de l'eau de cristallisation et du lactose amorphe d'un échantillon en analyse. Les pics et les changements de masse sur les thermogrammes TGA/SDTA caractéristiques de l'eau de surface, de l'eau de cristallisation et la teneur en lactose amorphe ont été identifiés. La teneur en eau de cristallisation a été utilisée pour estimer le lactose $\alpha$ monohydrate. La perte d'eau de surface se traduisait sur les thermogrammes TGA/SDTA par la perte de poids entre 40 et 130 °C, et la perte d'eau de cristallisation avait lieu à 153 °C. Le lactose amorphe était indiqué par un pic de cristallisation exothermique à 174 °C. La surface sous le pic de cristallisation exothermique était linéairement reliée à la proportion de lactose amorphe dans les mélanges avec lactose $\alpha$ monohydrate ($r = 0,989$). Ce travail présente les thermogrammes TGA/SDTA d'échantillons de lactose contenant quelques formes cristallines de lactose et de lactose amorphe. L'étude a comparé les méthodes pour déterminer les teneurs en eau de surface et en eau totale du lactose acceptées par les organismes officiels internationaux avec l'approche TGA/SDTA. Le potentiel de nouvelles méthodes pour détecter qualitativement les formes amorphes et cristallines du lactose par thermochimie et spectroscopie infrarouge à transformée de Fourier a également été exploré et comparé.
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ABSTRACT: The quantification of crystallinity is necessary in order to be able to control the milling process. The use of thermal analysis for this assessment presents certain challenges, particularly in the case of crystal hydrates. In this study, the residual crystallinity on ball milling of lactose monohydrate (LMH), for periods up to 90 min, was evaluated by thermo-analytical techniques (TGA, DSC) and terahertz spectroscopy (THz). In general, the results from one of the DSC analysis and the THz measurements agree showing a monotonous decrease in relative residual crystallinity with milling time (∼80% reduction after 60 min milling) and a slight increase at the 90 min time point. However, the estimates from TGA and two other methods of analyzing DSC curve do not agree with the former techniques and show variability with significantly higher estimates for crystallinity. Thermal techniques require more complex treatment of the data in the evaluation of changes in crystallinity of a milled material (in particular to account for the de-vitrification and mutarotation of the material that inevitably occurs during the measurement cycle) while the analysis of THz data is more straightforward, with the measurement having no impact on the native state of the material. Copyright © 2015. Published by Elsevier B.V.European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 03/2015; 92. DOI:10.1016/j.ejpb.2015.02.026 · 4.25 Impact Factor
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ABSTRACT: Dry powder inhaler formulations comprising commercial lactose–drug blends can show restricted detachment of drug from lactose during aerosolisation, which can lead to poor fine particle fractions (FPFs) which are suboptimal. The aim of the present study was to investigate whether the crystallisation of lactose from different ethanol/butanol co-solvent mixtures could be employed as a method of altering the FPF of salbutamol sulphate from powder blends. Lactose particles were prepared by an anti-solvent recrystallisation process using various ratios of the two solvents. Crystallised lactose or commercial lactose was mixed with salbutamol sulphate and in vitro deposition studies were performed using a multistage liquid impinger. Solid-state characterisation results showed that commercial lactose was primarily composed of the α-anomer whilst the crystallised lactose samples comprised a α/β mixture containing a lower number of moles of water per mole of lactose compared to the commercial lactose. The crystallised lactose particles were also less elongated and more irregular in shape with rougher surfaces. Formulation blends containing crystallised lactose showed better aerosolisation performance and dose uniformity when compared to commercial lactose. The highest FPF of salbutamol sulphate (38.0±2.5%) was obtained for the lactose samples that were crystallised from a mixture of ethanol/butanol (20:60) compared to a FPF of 19.7±1.9% obtained for commercial lactose. Engineered lactose carriers with modified anomer content and physicochemical properties, when compared to the commercial grade, produced formulations which generated a high FPF.
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ABSTRACT: In this study, lactose crystalline powder was produced to improve its stability. The effect of micronised crystalline lactose on a dry powder inhalation formulation was investigated. Supercritical carbon dioxide (scCO2) modified with menthol was used for the conditioning of spray-dried amorphous lactose and salbutamol sulphate to generate micro-spherical crystalline powders. The optimum processing conditions, which include: menthol concentration, temperature and processing time, were determined by experimental design to produce crystalline and a desired particle size. The average particle size of spray-dried amorphous lactose decreased from 8.15 ± 0.28 μm to 7.60 ± 0.10 μm after conditioning with modified CO2 at 150 bar and 50 °C for a period of 5 h. The SEM results shows that these particles kept their micro-spherical shape, however, the particle surface became rough due to crystallisation. This particle size reduction was most likely due to increasing surface roughness, which decreased agglomeration between particles. The blend of this fine powder and coarse crystalline lactose enhanced salbutamol sulphate inhalation performance. The emitted fine particle fraction of salbutamol sulphate was enhanced to 40 ± 0.3% compare to the samples that contained only coarse lactose (38.2 ± 0.6%) or conditioned lactose (24.6 ± 0.4%).Journal of Supercritical Fluids The 11/2012; 71:92–101. DOI:10.1016/j.supflu.2012.07.013 · 2.57 Impact Factor