Solvents effects on crystallinity and dissolution of ß-artemether.

ß-artemether (ARM) is a widely used anti-malarial drug isolated from the Chinese antimalarial plant, Artemisia annua. The solvent effects on crystal habits and dissolution of ARM were thoroughly investigated and discussed herein. The ARM was recrystallized in nine different solvents of varied polarity, namely, methanol, ethanol, isopropanol, tetrahydrofuran, dichloromethane, trichloromethane, ethyl acetate, acetone and hexane by solvent evaporation method. The obtained crystals were morphologically characterized using scanning electron microscope (SEM). The average sizes of crystals were 1.80-2.64 µm calculated from microscopic images using Image-Pro software. No significant change in chemical structure was noticed after recrystallization and the specific band at 875 cm-1 wavenumber (C-O-O-C) confirmed the presence of most sensitive functional group in the ARM chemical structure. The existence and production of two polymorphic forms, polymorph A and polymorph B, was confirmed by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The data suggested that the fabrication of polymorph B can be simply obtained from the recrystallization of ARM in a specific solvent. Significant effects of solvent polarity, crystals shapes and sizes on drug dissolution were noticed during in vitro dissolution test. The release kinetics were calculated and well fitted by the Higuchi and Hixon-Crowell models. The ARM-methanol and ARM-hexane showed highest and slowest dissolution, respectively, due to the effects of solvent polarity and crystal morphologies. Overall, proper selection of the solvents for the final crystallization of ARM helps to optimize dissolution and bioavailability for a better delivery of anti-malarial drug.

Impact of differential surface molecular environment on the interparticulate bonding strength of celecoxib crystal habits.

The present work investigates the impact of milling on differential compactibility behavior of celecoxib (CEL) crystal habits. Plate shaped (CEL-P) crystals showed better compactibility over acicular (CEL-A) crystals. Milling improved the compactibility of both the forms. However, despite similar particle shape, size, and surface area, milled fractions of the two habits showed significantly different interparticulate bonding strength. The greater bonding strength of milled CEL-P (MCEL-P) over milled CEL-A (MCEL-A) was attributed to the differential cleavage behavior of the two habits that conferred the different surface molecular environment to the milled powders. The preferred cleavage of CEL-P across {020} plane exposed the -CF3 group and the methyl phenyl ring on the surface of MCEL-P. On the other hand, CEL-A preferentially fractured along their shortest axis that increased the exposure of {100} plane on the surface of MCEL-A, which exposed the -CF3 group and the pyrazole ring. Surface free energy quantified by determining advancing contact angle revealed greater dispersive component of MCEL-P over MCEL-A. This is consistent with the differential cleavage behavior of CEL-P and CEL-A. This confirmed the role of dispersive component of surface free energy in governing interparticulate bonding strength of CEL. The study supports the postulate that tablet tensile strength is governed by the dispersive intermolecular interactions formed over the interparticulate bonding area.

Categorization of the main descriptors of different ampicillin crystal habits

With the purpose of enabling the analysis by digital methods of particles of multisource pharmaceutical raw materials, this study analyzed different crystal habits of ampicillin particles, by grouping the external shapes obtained from 3 different solvents (acetonitrile, ethanol, and methanol), thereby reducing the number of descriptors necessary to adequately represent each shape. For this purpose, a selection of morphological descriptors was used including: circularity, roughness, roundness, compactness, aspect ratio, effective diameter, solidity, convexity, fractal dimension, and 10 Complex Fourier descriptors. These measures cover highly diverse morphological properties and define the crystal habit of a particle. Principal Component Analysis (PCA) and the Cluster Analysis (CA) were the grouping techniques used, which demonstrated the possibility of using between 2 and 4 descriptors instead of the 18 proposed initially.

Com o objetivo de possibilitar a análise, por meio de métodos digitais, de partículas de matérias-primas farmacêuticas de múltiplas fontes, analisaram-se diferentes cristais de partículas de ampicilina através do agrupamento de formas externas obtidas de três diferentes solventes (acetonitrila, etanol e metanol), reduzindo, desse modo, o número de descritores necessários para representar adequadamente cada forma. Com esse propósito, utilizou-se seleção de descritores morfológicos, incluindo: circularidade, aspereza, arredondamento, compactação, relação de aspecto, diâmetro efetivo, solidez, convectividade, dimensão fractal e 10 descritores complexos de Fourier. Essas medidas cobrem diversas propriedades morfológicas e definem a cristalinidade de uma partícula. As análises do componente principal (PCA) e por grupamento (CA) foram as técnicas de agrupamento utilizadas, que demonstraram a possibilidade de utilizar entre 2 e 4 descritores ao invés dos 18, inicialmente propostos.