Impact of low molecular weight excipient octaacetylmaltose on the liquid crystalline ordering and molecular dynamics in the supercooled liquid and glassy state of itraconazole

Kamińska, Ewa; Tarnacka, Magdalena; Kołodziejczyk, K.; Dulski, Mateusz; Żakowiecki, Daniel; Hawełek, ᴌ.; Adrjanowicz, Karolina; Zych, Maria; Garbacz, Grzegorz; Kamiński, Kamil

doi:10.1016/j.ejpb.2014.10.002

Cited by 16 publications

(29 citation statements)

References 60 publications

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“…36,39,40 Another mechanism concerns the role of molecular mobility (both global, associated with α-relaxation, and local, linked to secondary processes) in inhibiting the crystallization. 25,26,30,33,41,42 Very recently Grzybowska et al have shown that the molecular mobility (reflected in the β-and γ-relaxations) of the solid dispersion formed by celecoxib (CEL) and acetylated maltose, acMAL (10% w/w), in the glassy state is much more limited than that in the case of pure CEL, which correlates with the better physical stability of the amorphous binary system. 30 In turn, Knapik et al investigated physicochemical properties of anticholesterol agent, ezetimibe (EZB), in a Soluplus (SOP) matrix.…”

Section: ■ Introductionmentioning

confidence: 97%

“…Moreover, a significant role of global mobility in controlling the crystallization ability has been shown by Bhardway et al for an amorphous system formed between itraconazole (ITZ) and two polymers: polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose acetate succinate (HPMCAS); 41 Aso et al for nifedipine (NIF)-PVP solid dispersions 42 and by us for ITZ−acMAL molecular dispersion. 33 Numerous studies have also discussed the potential role of specific interactions (e.g., hydrogen bonding, dipole−dipole, ion−dipole, and electrostatic forces) in improving the stability of amorphous APIs. 1,8,23,24,27−32,40,43−48 For example, Matsumoto et al have studied amorphous solid dispersions formed between indomethacin (IMC) and various molecular weight grades of PVP and poly(vinylpyrrolidone-co-vinylacetate), PVP/VA.…”

Section: ■ Introductionmentioning

confidence: 99%

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Studying the Impact of Modified Saccharides on the Molecular Dynamics and Crystallization Tendencies of Model API Nifedipine

et al. 2015

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Molecular dynamics of pure nifedipine and its solid dispersions with modified carbohydrates as well as the crystallization kinetics of active pharmaceutical ingredient (API) above and below the glass transition temperature were studied in detail by means of broadband dielectric spectroscopy (BDS), differential scanning calorimetry (DSC), and X-ray diffraction method. It was found that the activation barrier of crystallization increases in molecular dispersions composed of acetylated disaccharides, whereas it slightly decreases in those consisting of modified monocarbohydrates for the experiments carried out above the glass transition temperature. As shown by molecular dynamics simulations it can be related to the strength, character, and structure of intermolecular interactions between API and saccharides, which vary dependently on the excipient. Long-term physical stability studies showed that, in solid dispersions consisting of acetylated maltose and acetylated sucrose, the crystallization of nifedipine is dramatically slowed down, although it is still observable for a low concentration of excipients. With increasing content of modified carbohydrates, the crystallization of API becomes completely suppressed. This is most likely due to additional barriers relating to the intermolecular interactions and diffusion of nifedipine that must be overcome to trigger the crystallization process.

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Section: ■ Introductionmentioning

confidence: 97%

Section: ■ Introductionmentioning

confidence: 99%

Studying the Impact of Modified Saccharides on the Molecular Dynamics and Crystallization Tendencies of Model API Nifedipine

et al. 2015

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“…Taking into account the abovementioned problem, the interesting alternatives for polymers are low-molecular weight EXCs. Among them, amino acids, − small proteins, , organic acids, other active substances, − and carbohydrates and their modified analogues − (prepared by substituting the hydrogen atom from hydroxyl groups by hydrophobic, e.g., acetyl moieties) are commonly applied to stabilize amorphous APIs. From the mentioned groups, saccharides deserve special attention.…”

Section: Introductionmentioning

confidence: 99%

Impact of the Chain Length and Topology of the Acetylated Oligosaccharide on the Crystallization Tendency of Naproxen from Amorphous Binary Mixtures

et al. 2020

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The impact of the chain length or dispersity of polymers in controlling the crystallization of amorphous active pharmaceutical ingredients (APIs) has been discussed for a long time. However, because of the weak control of these parameters in the majority of macromolecules used in pharmaceutical formulations, the abovementioned topic is poorly understood. Herein, four acetylated oligosaccharides, maltose (acMAL), raffinose (acRAF), stachyose (acSTA), and α-cyclodextrin (ac-α-CD) of growing chain lengths and different topologies (linear vs cyclic), mimicking the growing backbone of the polymer, were selected to probe the influence of these structural factors on the crystallization of naproxen (NAP)—an API that does not vitrify regardless of the cooling rate applied in our experiment. It was found that in equimolar systems composed of NAP and linear acetylated oligosaccharides, the progress and activation barrier for crystallization are dependent on the molecular weight of the excipient despite the fact that results of Fourier transform infrared studies indicated that there is no difference in the interaction pattern between measured samples. On the other hand, complementary dielectric, calorimetric, and X-ray diffraction data clearly demonstrated that NAP mixed with ac-α-CD (cyclic saccharide) does not tend to crystallize even in the system with a much higher content of APIs. To explain this interesting finding, we have carried out further density functional theory computations, which revealed that incorporation of NAP into the cavity of ac-α-CD is hardly possible because this state is of much higher energy (up to 80 kJ/mol) with respect to the one where the API is located outside of the saccharide torus. Hence, although at the moment, it is very difficult to explain the much stronger impact of the cyclic saccharide on the suppression of crystallization and enhanced stability of NAP with respect to the linear carbohydrates, our studies clearly showed that the chain length and the topology of the excipient play a significant role in controlling the crystallization of this API.

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“…Acetylated starch is classified by the Food and Drug Administration (FDA) as a Generally Recognized as Safe (GRAS) material. Numerous investigations regarding the use of various sugar derivatives, i.e., acetylated sucrose, glucose, maltose, galactose, to stabilize amorphous forms of drugs, such as indomethacin, itraconazole, and nifedipine have been published (6,17,18). Solid dispersions composed of amorphous APIs have been obtained by melting with appropriate ratios of active substances and modified saccharides followed by rapid cooling.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, it has been found that the amorphous form of API remained stable even after 1 year of storage under room conditions (22). In this context, application of acetylated saccharides in the formulation seems to be a promising option (11,17,18).…”

Section: Introductionmentioning

confidence: 99%

Melts of Octaacetyl Sucrose as Oral-Modified Release Dosage Forms for Delivery of Poorly Soluble Compound in Stable Amorphous Form

Haznar-Garbacz

Kamińska

Żakowiecki³

et al. 2017

AAPS PharmSciTech

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Abstract. The presented work describes the formulation and characterization of modified release glassy solid dosage forms (GSDFs) containing an amorphous nifedipine, as a model BCS (Biopharmaceutical Classification System) class II drug. The GSDFs were prepared by melting nifedipine together with octaacetyl sucrose. Dissolution profiles, measured under standard and biorelevant conditions, were compared to those obtained from commercially available formulations containing nifedipine such as modified release (MR) tablets and osmotic release oral system (OROS). The results indicate that the dissolution profiles of the GSDFs with nifedipine are neither affected by the pH of the dissolution media, type and concentration of surfactants, nor by simulated mechanical stress of biorelevant intensity. Furthermore, it was found that the dissolution profiles of the novel dosage forms were similar to the profiles obtained from the nifedipine OROS. The formulation of GSDFs is relatively simple, and the dosage forms were found to have favorable dissolution characteristics.

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Impact of low molecular weight excipient octaacetylmaltose on the liquid crystalline ordering and molecular dynamics in the supercooled liquid and glassy state of itraconazole

Cited by 16 publications

References 60 publications

Studying the Impact of Modified Saccharides on the Molecular Dynamics and Crystallization Tendencies of Model API Nifedipine

Studying the Impact of Modified Saccharides on the Molecular Dynamics and Crystallization Tendencies of Model API Nifedipine

Impact of the Chain Length and Topology of the Acetylated Oligosaccharide on the Crystallization Tendency of Naproxen from Amorphous Binary Mixtures

Melts of Octaacetyl Sucrose as Oral-Modified Release Dosage Forms for Delivery of Poorly Soluble Compound in Stable Amorphous Form

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