Characterisation and fundamental insight into the formation of new solid state, multicomponent systems of propranolol

Bialek, Klaudia; Wojnarowska, Ż.; Twamley, Brendan; Tajber, Lidia

doi:10.1016/j.ijpharm.2021.120605

Cited by 3 publications

(8 citation statements)

References 55 publications

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“…Therefore, it can be concluded that the reaction between CAP and PRO occurring in the solid state is facilitated by the formation of a metastable submerged eutectic, in addition to two other eutectic phases, EUT1 and EUT2, at higher temperatures identified by DSC (Figure 5a). This is also why no exotherm, leading to the salt formation, was recorded by DSC, as described for dipropranolol sebacate [25]. The temperature at which the eutectic between PRO and CAP would melt can be theoretically predicted using the Schroeder van Laar equation [44].…”

Section: Characterisation Of Propranolol Caprate Saltmentioning

confidence: 87%

“…The PRO base was obtained from the PRO•HCl salt as previously described by Bialek et al [25]. Briefly, a quantity of 1 g of PRO•HCl was dissolved in 50 mL of deionised water.…”

Section: Sample Preparation Pro Free Base Synthesismentioning

confidence: 99%

“…2.2.5. Differential Scanning Calorimetry (DSC) DSC measurements were carried out using a PerkinElmer Diamond DSC unit (Waltham, MA, USA) equipped with a ULSP B.V. 130 cooling system (Ede, Netherlands) [25]. Nitrogen (40 mL/min) was used as the purge gas.…”

Section: Solution and Solid-state Nuclear Magnetic Resonance (Nmr)mentioning

confidence: 99%

“…The samples were analysed from 2 to 40 • on the 2θ scale at a step size of 0.05 • per second at room temperature. The samples were supported by a zero-background silicon sample holder (Rigaku, Tokyo, Japan) during analysis [25].…”

Section: Powder X-ray Diffraction (Pxrd)mentioning

confidence: 99%

“…We previously investigated a binary system of PRO and sebacic acid [25]. Sebacic acid is the equivalent dicarboxylic acid of capric acid (CAP), and its structure is presented in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

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Submerged Eutectic-Assisted, Solvent-Free Mechanochemical Formation of a Propranolol Salt and Its Other Multicomponent Solids

et al. 2021

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Salt preparation via a solid-state reaction offers a solution to challenges posed by current pharmaceutical research, which include combining development of novel forms of active pharmaceutical ingredients with greener, sustainable synthesis. This work investigated in detail the mechanism of salt formation between propranolol (PRO) and capric acid (CAP) and explored the solid eutectic phases comprising this salt, propranolol caprate (PRC). The salt structure was solved by X-ray diffraction, and the properties in the crystalline and supercooled states were fully characterised using thermal analysis, nuclear magnetic resonance, Fourier-transform infrared spectroscopy and broadband dielectric spectroscopy (BDS). PRC forms via a submerged eutectic phase composed of PRO and CAP, below room temperature, by mechanochemistry without an extra input of energy. Two other solid eutectic phases are composed of PRC and either CAP or PRO, at 0.28 and 0.82 mol fraction of PRO, respectively. BDS indicated that the supercooled PRC has ionic character, whereas the supercooled PRC-PRO eutectic had predominantly non-ionic properties despite comprising the salt. In conclusion, knowledge of the mechanism of formation of multicomponent systems can help in designing more sustainable pharmaceutical processes.

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Section: Characterisation Of Propranolol Caprate Saltmentioning

confidence: 87%

“…The PRO base was obtained from the PRO•HCl salt as previously described by Bialek et al [25]. Briefly, a quantity of 1 g of PRO•HCl was dissolved in 50 mL of deionised water.…”

Section: Sample Preparation Pro Free Base Synthesismentioning

confidence: 99%

Section: Solution and Solid-state Nuclear Magnetic Resonance (Nmr)mentioning

confidence: 99%

Section: Powder X-ray Diffraction (Pxrd)mentioning

confidence: 99%

“…We previously investigated a binary system of PRO and sebacic acid [25]. Sebacic acid is the equivalent dicarboxylic acid of capric acid (CAP), and its structure is presented in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

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Submerged Eutectic-Assisted, Solvent-Free Mechanochemical Formation of a Propranolol Salt and Its Other Multicomponent Solids

et al. 2021

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Propranolol-loaded nanostructured lipid carriers for topical treatment of infantile hemangioma

Rocha

Pires

Gross

et al. 2023

Journal of Drug Delivery Science and Technology

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Impact of the Dicarboxylic Acid Chain Length on Intermolecular Interactions with Lidocaine

2022

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Acid–base multicomponent systems have become a popular choice as a strategy to fine-tune the physicochemical properties of active pharmaceutical ingredients. Current prediction tools based on the principles of anticrystal engineering cannot always accurately predict the nature of intermolecular interactions within a multicomponent system. Even small changes in the physicochemical parameters of parent components can result in unexpected outcomes, and many salt, cocrystal, and ionic liquid forms are still being discovered empirically. In this work, we aimed to establish structural consistency in a series of mixtures comprising lidocaine (LID) with decanedioic, undecanedioic, dodecanedioic, and tridecanedioic acids and to explore how length and flexibility of the acid carbon backbone affect the molecular recognition, crystallization, and thermal behavior of the expected binary systems. We found that neat grinding of LID with dicarboxylic acids results in the formation of eutectic phases. The observed eutectic melting points deviated from the ideal eutectic temperatures predicted by the Schroeder van Laar model because of hydrogen bonding between the reacting components within the mixtures. Furthermore, thermal and infrared analysis provided evidence for the possible formation of new phases stemming from partial ionization of the counterions. Besides, the structure of a previously undetermined form I of the tridecanedioic acid was solved by single crystal X-ray diffraction.

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Characterisation and fundamental insight into the formation of new solid state, multicomponent systems of propranolol

Cited by 3 publications

References 55 publications

Submerged Eutectic-Assisted, Solvent-Free Mechanochemical Formation of a Propranolol Salt and Its Other Multicomponent Solids

Submerged Eutectic-Assisted, Solvent-Free Mechanochemical Formation of a Propranolol Salt and Its Other Multicomponent Solids

Propranolol-loaded nanostructured lipid carriers for topical treatment of infantile hemangioma

Impact of the Dicarboxylic Acid Chain Length on Intermolecular Interactions with Lidocaine

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