Systematic evaluation of the impact of solid-state polymorphism on the bioavailability of thalidomide

Active pharmaceutical ingredients (API) are the main components in the production process of pharmaceutical products. If the API has a good quality, then it will lead to good pharmaceutical products. API consists of more than one different crystal form which, then forms a polymorph through the process of polymorphism. Until now, API polymorphism is still a big challenge in the pharmaceutical industry. That is because the nature of polymorphism is difficult to predict. One of them is by crystallizing molecules in one or many crystalline forms or combining with other molecules to form stable co-crystal. This process will lead to several polymorph forms of one certain API. Sometimes, these forms will have characteristics that differ one to another. Each polymorph has different mechanical, physical, thermal, and chemical properties that will affect the solubility, dissolution, bioavailability, stability, bioequivalence, and manufacturing of the API. Therefore to know the nature of an API, it is necessary to characterize the polymorphic form of the API before. If the form is not incompatible with the formulation, it can cause a failure in the production process. This review will discuss the effect of polymorphism on the physicochemical properties of API. It is hoped that this review can become the basis for improving the stability and effectiveness of pharmaceutical products.

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“…Then the test was carried out with SI and q values using a sink condition with a 500 mL surfactant medium. (Oliveira et al, 2019).…”

Section: Bioavailabilitymentioning

confidence: 99%

“…However, the speed and high extension of the dissolution test on α-TLD illustrates good pharmacokinetics and bioavailability. It is recommended that the pharmaceutical industry use polymorph α-TLD as an active ingredient (Oliveira et al, 2019).…”

Section: Bioavailabilitymentioning

confidence: 99%

The effect of polymorphism on active pharmaceutical ingredients: A review

Ainurofiq

Dinda

Pangestika

et al. 2020

ijrps

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“…Log P characterize the hydrophilic or lipophilic character of a molecule (Chmiel et al, 2019) and calculated by the logarithm of the partition coefficient between octanol and water. It is used to evaluate the bioavailability of a molecule: Log P< 0, the molecule is said hydrophilic; Log P >5, the molecule is lipophilic; A good balance is needed between the hydrophilic and hydrophobic character for an optimal biological activity 0<Log P<5 (de Oliveira et al, 2019). A molecule with an optimal biological activity is sufficiently hydrophilic to be soluble in aqueous media (blood, cytoplasm...) and in the same time it must have a hydrophobic character to pass through the membranes (Pieńko et al, 2016).…”

Section: Physicochemical Propertiesmentioning

confidence: 99%

Theoretical Investigation of Two Antiemetic Drugs at DFT Level

Kanouni¹,

Benguerba²

2020

Current Research in Bioinformatics

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The geometries and the bonding properties have been predicted for two antiemetic drugs using Density Functional Theory method (DFT). Mulliken population and frontier molecular orbital analysis with the determination of the physicochemical properties was performed using the Amsterdam Density Functional package (ADF). To calculate the exchangecorrelation energy, the Generalized Gradient Approximation of Becke-Perdew (GGA-BP) was used. The most important finding is the still acceptable reliability of this method in predicting the physicochemical properties for the two organic drugs used in this study. The theoretical results obtained from the ADF software are compared with experimental ones obtained from literature. It was showed that the calculated properties were satisfactorily close to the experimental ones.

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“…As the physicochemical properties of a drug can influence its performance in formulation processing and later its bioavailability, the fundamental concept of its crystalline state should be understood before formulation design (Datta & Grant, 2004). For instance, numerous drug entities have been evaluated on their polymorph transformation in recent years (Zhang & Chen, 2017;Zanolla et al, 2018;Paczkowska et al, 2018;de Oliveira et al, 2019;Salazar-Rojas et al, 2020). On the other hand, amorphous content has been proved to increase the solubility and dissolution rate in amorphous solid dispersion (ASD) (Mendes et al, 2019;Kwon et al, 2019;Angi et al, 2019;Pinto et al, 2020;Teoh et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Exploring solid states of atovaquone: crystal or glass?

Teoh¹,

Teh²,

Chan³

2022

J Appl Cryst

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Formulation design is necessary to improve drug solubility, particularly for drugs in Biopharmaceutics Classification System (BCS) classes II and IV. The formulating decision is often affected by the drug's physicochemical properties. To complement the available knowledge, the thermal and structural properties of atovaquone have been investigated. Heat was applied to raw atovaquone to observe the effect of temperature on crystalline polymorphic changes and physical state conversion. Physicochemical properties were assessed through drug content assay, differential scanning calorimetry, X-ray powder diffraction, single-crystal X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy. The surface morphology was observed under a scanning electron microscope. Thermal degradation of atovaquone was confirmed through drug recovery and the sublimating behaviour was observed during the heating process. Understanding the fundamental thermal and structural characteristics of atovaquone plays an important role in designing a stable product of high bioavailability.

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Systematic evaluation of the impact of solid-state polymorphism on the bioavailability of thalidomide

Cited by 7 publications

References 42 publications

The effect of polymorphism on active pharmaceutical ingredients: A review

The effect of polymorphism on active pharmaceutical ingredients: A review

Theoretical Investigation of Two Antiemetic Drugs at DFT Level

Exploring solid states of atovaquone: crystal or glass?

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