Effect of Temperature and Moisture on the Physical Stability of Binary and Ternary Amorphous Solid Dispersions of Celecoxib

Xie, Tian; Taylor, Lynne S.

doi:10.1016/j.xphs.2016.06.017

Cited by 65 publications

(50 citation statements)

References 44 publications

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“…Thus, water molecules present in kaolin could probably be the main factor for lowering the temperature of glass transition event [33]. Taylor et al have shown that the modifications of the T g of drug/carrier solid dispersions are not always predictive for crystallization tendency; several solid dispersions in the presence of different polymers (PVP/PVP VA) underwent a decrease in T g due to the presence of water molecules but they still maintain its physical stability thanks to intermolecular interactions between drug and carrier [34].…”

Section: Ternary System (Ind/kaolin/pvp)mentioning

confidence: 99%

The Effect of Adding PVP to the Binary Solid Dispersion (Indomethacin: Kaolin) on the Formation of Physically Stable Amorphous Drug

Béjaoui¹,

Kalfat²,

Galai³

2021

J Pharm Innov

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Purpose In this work, we investigate the effect of adding polyvinylpyrrolidone (PVP K30) to the binary solid dispersion (indomethacin/kaolin) on the formation of physically stable amorphous drug. This aims to profit more effectively from the therapeutic effect of kaolin in the solid dosage forms of indomethacin. Methods Binary mixtures (indomethacin/kaolin) were ball milled at room temperature (≈ 25 °C) in presence of PVP K30 at different weight ratios (w/w). The characterization of the obtained materials was carried out using X-ray diffraction (XRD), infrared spectroscopy (FTIR), scanning electronic microscopy (SEM), high-performance liquid chromatography (HPLC), differential scanning calorimetry (DSC), and 13 C MAS NMR spectroscopy. Results Results have shown that indomethacin (IND) interacted with kaolin and PVP K30 in solid state via hydrogen bonds without any polymorphic transformations or chemical degradation. The PVP seems to play a role of linker between drug and kaolin leading to physical stability enhancement of amorphous IND even under high stress conditions (RH = 75% and T = 40 °C for 3 months). Such ternary system (IND/kaolin/PVP) has shown a considerable improvement of drug solubility at T = 37 ± 0.5 °C and pH = 7.0 compared to the binary solid dispersion (IND/kaolin). Conclusions The addition of PVP to the solid dispersion (IND/kaolin) was advantageous not only in terms of physical stabilization of the amorphous IND but also made it possible to overcome the solubility challenges associated with the presence of kaolin.

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Section: Ternary System (Ind/kaolin/pvp)mentioning

confidence: 99%

The Effect of Adding PVP to the Binary Solid Dispersion (Indomethacin: Kaolin) on the Formation of Physically Stable Amorphous Drug

Béjaoui¹,

Kalfat²,

Galai³

2021

J Pharm Innov

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“…The amounts of excipients are expected to be larger compared to that for Class 3 compounds. Typically, solid solubility of drug in polymeric matrix under ambient temperature is below 30%, sometimes below 10%, depending on combination of drug and excipient [21,22,23]. Moreover, it is frequently observed that the effective polymer for physical stabilization and dissolution improvement is different.…”

Section: Relevance To Formulation Researchmentioning

confidence: 99%

“…Polymeric excipients in ASDs serve not only for improving the supersaturation behavior as mentioned above, but also for inhibiting crystallization of the drug. Miscibility is an important factor for exploiting the stabilization effect by the polymer [21,22,23]. Obviously, the crystallization tendency of the drug molecule itself is another important factor affecting the storage stability.…”

Section: Introductionmentioning

confidence: 99%

Crystallization Tendency of Pharmaceutical Glasses: Relevance to Compound Properties, Impact of Formulation Process, and Implications for Design of Amorphous Solid Dispersions

Kawakami

2019

Pharmaceutics

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Amorphous solid dispersions (ASDs) are important formulation strategies for improving the dissolution process and oral bioavailability of poorly soluble drugs. Physical stability of a candidate drug must be clearly understood to design ASDs with superior properties. The crystallization tendency of small organics is frequently estimated by applying rapid cooling or a cooling/reheating cycle to their melt using differential scanning calorimetry. The crystallization tendency determined in this way does not directly correlate with the physical stability during isothermal storage, which is of great interest to pharmaceutical researchers. Nevertheless, it provides important insights into strategy for the formulation design and the crystallization mechanism of the drug molecules. The initiation time for isothermal crystallization can be explained using the ratio of the glass transition and storage temperatures (Tg/T). Although some formulation processes such as milling and compaction can enhance nucleation, the Tg/T ratio still works for roughly predicting the crystallization behavior. Thus, design of accelerated physical stability test may be possible for ASDs. The crystallization tendency during the formulation process and the supersaturation ability of ASDs may also be related to the crystallization tendency determined by thermal analysis. In this review, the assessment of the crystallization tendency of pharmaceutical glasses and its relevance to developmental studies of ASDs are discussed.

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“…Kinetically, moisture can lead to a plasticizing effect (reducing the systemic T g ), thereby increasing overall molecular mobility and the risk for recrystallization. Furthermore, the absorbed water has the potential to disrupt drug-polymer interactions by competing with hydrophilic polymers to form hydrogen bonds with APIs [33]. It was also implied in some studies that moisture uptake could reduce the drug-polymer solubility, and the extent of such effects varied with different APIs [34,35].…”

Section: Environmental Factors Affecting the Physical Stability Of Asdsmentioning

confidence: 99%

Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

et al. 2020

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The thermodynamically unstable nature of amorphous drugs has led to a persistent stability issue of amorphous solid dispersions (ASDs). Lately, microwave-induced in situ amorphization has been proposed as a promising solution to this problem, where the originally loaded crystalline drug is in situ amorphized within the final dosage form using a household microwave oven prior to oral administration. In addition to circumventing issues with physical stability, it can also simplify the problematic downstream processing of ASDs. In this review paper, we address the significance of exploring and developing this novel technology with an emphasis on systemically reviewing the currently available literature in this pharmaceutical arena and highlighting the underlying mechanisms involved in inducing in situ amorphization. Specifically, in order to achieve a high drug amorphicity, formulations should be composed of drugs with high solubility in polymers, as well as polymers with high hygroscopicity and good post-plasticized flexibility of chains. Furthermore, high microwave energy input is considered to be a desirable factor. Lastly, this review discusses challenges in the development of this technology including chemical stability, selection criteria for excipients and the dissolution performance of the microwave-induced ASDs.

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Effect of Temperature and Moisture on the Physical Stability of Binary and Ternary Amorphous Solid Dispersions of Celecoxib

Cited by 65 publications

References 44 publications

The Effect of Adding PVP to the Binary Solid Dispersion (Indomethacin: Kaolin) on the Formation of Physically Stable Amorphous Drug

The Effect of Adding PVP to the Binary Solid Dispersion (Indomethacin: Kaolin) on the Formation of Physically Stable Amorphous Drug

Crystallization Tendency of Pharmaceutical Glasses: Relevance to Compound Properties, Impact of Formulation Process, and Implications for Design of Amorphous Solid Dispersions

Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

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