Granulation and Production Approaches of Orally Disintegrating Tablets
Dilip M. Parikh in Handbook of Pharmaceutical Granulation Technology, 2021
An eutectic system is a combination of different materials that freeze (also melt or solidify) in a temperature lower than either of its components. Water-soluble drug molecules form eutectic systems with the excipients, thus the freezing process remains incomplete during the lyophilization process. This results in the collapse of the system upon drying because of missing the backbone excipient system during the sublimation. In such cases, the employment of materials such as mannitol, which is capable of forming matrixes and inducing crystallinity, can help to increase the rigidity of matrix along with masking the taste of drugs [40]. According to some literature [41], the maximum dose for a hydrophilic drug molecule in an ODT formulation is 60 mg, while this amount is defined as 400 mg for the hydrophobic drugs because it has been evidenced that hydrophobic molecules could also create aggregates upon sublimation due to the high molecular weight.
Structures and Properties of Self-Assembled Phospholipids in Excess Water
E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson in Phospholipid-Binding Antibodies, 2020
When two phosopholipids are partially miscible in the gel phase and completely miscible in the fluid phase, the binary phase diagram may look like Figure 9B, which is for C( 18):C( 10)PC/C( 14):C( 14)PC mixtures.70 Such phase diagrams, constructed based on the onset and completion temperatures of phase transition curves obtained at various molar ratios of the mixtures, have a shape which is the hallmark of a eutectic system. In this system, there are three one-phase regions (G1, G2 and F), three two-phase regions (F + Gl5 F + G2 and Gi + G2), and one degenerated three-phase region, the eutectic point at a fixed temperature and composition. Of course, the three phases co-existing in equilibrium at the eutectic point are the maximum number of phases allowed to co-exist for the binary lipid mixtures, in excess water, at constant pressure according to the phase rule.66 In the case of C(18):C(10)PC/C(14):C(14)PC, the eutectic point is at 13.4°C and 40% of C(14):C(14)PC.
Hormesis
T. D. Luckey in Radiation Hormesis, 2020
Hormology is the study of excitation. It includes physical, and chemical, as well as biologic vectors. One example is the melting point of a mixture of two metals. Addition of one to the other lowers the melting point until the eutectic point is reached; then adding more of the same metal to the mixture increases the melting point (Figure 2.3). This example shows clearly that small and large doses of a single agent evoke opposite effects.
Ternary solid dispersions: classification and formulation considerations
Published in Drug Development and Industrial Pharmacy, 2021
Shambhavi Borde, Sagar Kumar Paul, Harsh Chauhan
The melting method, which is also known as the fusion method, is a simple and commonly used method for the production of solid dispersions. This process simply comprises the heating of materials followed by cooling. The components are melted together at a temperature above the eutectic point. The molecular mobility of this eutectic mixture is high enough to allow the drug particle to successfully occupy in the matrix, which results in decreased drug particle size and better wettability. In this process, the cooling rate is also crucial as it can affect the type of incorporation of the drug in the matrix [111]. This melted homogenous mixture is then solidified by different techniques, such as using a freezer, using an ice bath, spreading a thin layer on stainless steel cooled by air draft, spreading it on plates placed over dry ice, immersing in liquid nitrogen, or grinding the material in liquid nitrogen (cryo-grinding), pouring it into petri dishes placed at room temperature inside a desiccator [96]. For example, Pacult et al. prepared a D–D–P TSD by melting the physical mixture of materials on a hot plate and then vitrifying it by previously chilled copper plate [88]. After this, several other processes like crushing, pulverizing, and sieving are conducted to get the final solid dispersion powder.
Melting point depression for enhanced dissolution rate of eslicarbazepine acetate
Published in Drug Development and Industrial Pharmacy, 2023
Ebtehal M. Dorgham, Gamal M. El Maghraby, Ebtessam A. Essa, Mona F. Arafa
Modulation of drug crystallinity can be utilized as an approach for enhancing drug dissolution. This can employ co-crystal formation, co-amorphousization or eutectic mixture formation. Eutectic system is mixture of different compounds which melt at temperature that is lower than the melting temperature of the individual components developing homogenous system. The depression in the melting point reveals the weakness of intermolecular bonds. This is reflected on the drug dissolution rate that is considerably enhanced [4]. Eutectic mixtures can be fabricated using either drug with an inert material or by mixing two drugs with different solubility [4–6].
Deep eutectic solvents comprising active pharmaceutical ingredients in the development of drug delivery systems
Published in Expert Opinion on Drug Delivery, 2019
Sónia N. Pedro, Mara G. Freire, Carmen S. R. Freire, Armando J. D. Silvestre
DES are eutectic mixtures that deviate from the ideal thermodynamic solid-liquid phase behavior, i. e. a mixture of pure compounds for which the eutectic point temperature is below than that of an ideal liquid mixture (Figure 1) [20,21]. Strong hydrogen-bond interactions between the HBD and HBA species that form the DES are responsible for a decrease in the melting temperature to such a degree where the mixture can be liquid at room or human body’s temperature [22]. DES, unlike ILs, are mixtures, and not pure compounds, and can be at best a solution of ions and not a fluid constituted solely by ionic species [21]. DES preparation usually involves the simple mixing of at least two components, generally under stirring and moderate heating [23]. Importantly, the temperature to which the mixture is subjected must be carefully controlled to prevent the decomposition of the individual components that make up the DES [24]. Since no chemical reaction is involved in the preparation process (it presents 100% of the atom economy and fits within one of the Green Chemistry principles), there is also no formation of by-products [25]. Thus, their purity is only dependent on the purity of the individual starting components and on the avoidance of degradation products. This being said, the toxicity of the final mixture must be carefully assessed since significant differences from the individual constituents might be observed [26–28]. To overcome some of the cytotoxicity concerns related with DES, especially when their human consumption is envisaged, the research on natural DES (NADES) has been recently expanded [29]. Furthermore, due to the possibility of combining an enormous number of HBDs and HBAs, NADES can be considered tailor-made solvents with high interest in biomedical and pharmaceutical applications [30,31]. As such, DES comprising the API as the HBD or HBA species or as solvents to improve the solubility of target APIs have been studied.
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