Naftopidil Molecular Salts with Improved Dissolution and Permeation

Mannava, M. K. Chaitanya; Dandela, Rambabu; Tothadi, Srinu; Solomon, K. Anand; Nangia, Ashwini

doi:10.1021/acs.cgd.9b01689

Cited by 26 publications

(24 citation statements)

References 32 publications

(47 reference statements)

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“…Polymorphs, solvates, and hydrates have limited existence. During the last decade, the cocrystallization method was applied to APIs to improve their physicochemical and processability properties without affecting their therapeutic role as a drug ( Schultheiss and Newman, 2009 ; Mannava et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Pharmaceutical Cocrystals: From Bench to Market

Bandaru¹,

Rout²,

Kenguva³

et al. 2021

Front. Pharmacol.

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The pharmacokinetics profile of active pharmaceutical ingredients (APIs) in the solid pharmaceutical dosage forms is largely dependent on the solid-state characteristics of the chemicals to understand the physicochemical properties by particle size, size distribution, surface area, solubility, stability, porosity, thermal properties, etc. The formation of salts, solvates, and polymorphs are the conventional strategies for altering the solid characteristics of pharmaceutical compounds, but they have their own limitations. Cocrystallization approach was established as an alternative method for tuning the solubility, permeability, and processability of APIs by introducing another compatible molecule/s into the crystal structure without affecting its therapeutic efficacy to successfully develop the formulation with the desired pharmacokinetic profile. In the present review, we have grossly focused on cocrystallization, particularly at different stages of development, from design to production. Furthermore, we have also discussed regulatory guidelines for pharmaceutical industries and challenges associated with the design, development and production of pharmaceutical cocrystals with commercially available cocrystal-based products.

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Section: Introductionmentioning

confidence: 99%

Recent Advances in Pharmaceutical Cocrystals: From Bench to Market

Bandaru¹,

Rout²,

Kenguva³

et al. 2021

Front. Pharmacol.

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“…The multicomponent solids exhibited biphasic drug release in which the release rate was faster in the initial 1 h, followed by slower release until the end of the diffusion experiment (Figure c) . Flux was derived from the slope of the linear portion of the plot on cumulative drug release per unit area vs time.…”

Section: Results and Discussionmentioning

confidence: 99%

“…Both the cocrystals and salts are reported to improve the diffusion/permeability of a small number of drugs, 10,43 although a few studies have elaborated that there is no significant improvement in the drug diffusion. 12,13,43 In the present context, ECB constitutes cocrystals/salts with different coformers of varying log P values. ECB has a log P of −0.43, which indicates the hydrophilic nature of the drug; hence, the influence of log P of the coformers on the diffusion of the multicomponent solids was investigated.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…12 The multicomponent solids exhibited biphasic drug release in which the release rate was faster in the initial 1 h, followed by slower release until the end of the diffusion experiment (Figure 9c). 43 Flux was derived from the slope of the linear portion of the plot on cumulative drug release per unit area vs time. The initial flux of the drug was rapid as observed from the slope of all the multicomponent systems until 1 h, followed by decreased flux; see Table 3.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Tuning Diffusion Permeability of an Anti-Retroviral Drug, Emtricitabine, via Multicomponent Crystallizations

Palanisamy

Sanphui

Jyothi

et al. 2021

Crystal Growth & Design

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Emtricitabine (ECB) is an anti-retroviral drug that inhibits HIV reverse transcriptase and prevents transcription of RNA to DNA. ECB exhibits high solubility and low permeability (log P < 0). To modify the diffusion behavior of ECB, a high throughput cocrystal screening has been carried out with coformers that contain carboxylic acid/amide functionalities via solvent assisted grinding. The screening study resulted in the formation of cocrystals with benzoic acid (BA), caprolactam (CPR), and salts with 2,6-dihydroxybenzoic acid (DHBA), malonic acid (MLN), maleic acid (MLE), and saccharin (SAC), which were confirmed with single crystal X-ray diffraction. In addition, 15N solid state NMR spectroscopy was exploited to define the ionization state of the multicomponent systems. The 2-aminopyrimidine homodimer of the cytosine analogue in the ECB is replaced by aminopyrimidine···carboxylic acid/amide in the cocrystals and aminopyrimidinium···carboxylate/saccharinate heterosynthons in the salts. The terminal hydroxyl group of the ECB forms a hydrogen bond with its carbonyl group, which is consistent in the ECB–BA cocrystal, ECB–DHBA and ECB–MLN salts. In addition, the hydroxyl group of ECB is hydrogen bonded with the relatively stronger acceptors like the carbonyl/sulfonyl group of caprolactam, maleate, and saccharinate in their corresponding multicomponent crystals. The diffusion studies of ECB multicomponent crystals using a Franz diffusion cell suggest that the ECB–BA cocrystal exhibited an enhanced diffusion and flux compared to that of native drug and other multicomponent crystals. An inverse correlation was observed partially between the flux values with crystal densities and binding energies of the ECB multicomponent systems.

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“…Recent studies report both the crystal structures and the properties of the prepared salts. Unfortunately, most of them contain a relatively small number of samples (Sanphui et al, 2014;Mannava et al, 2020;Gunnam & Nangia, 2019;Banik et al, 2016;Martin et al, 2013;Thakuria & Nangia, 2013;Goud et al, 2013). Several studies with systematic large datasets are now available (20-50 salts) that bring new insight into this topic (de Moraes et al, 2017;Arlin et al, 2011;Collier et al, 2006;Black et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Structure–property relations of a unique and systematic dataset of 19 isostructural multicomponent apremilast forms

Jirát¹,

Babor²,

Ridvan³

et al. 2022

Int Union Crystallogr J

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The structure–property relations are examined for apremilast cocrystals and solvates in this work. A unique and large dataset of multicomponent crystal forms is presented including 7 cocrystals and 12 solvates. In total, 15 of the presented multicomponent forms and their crystal structures are published here for the first time. This dataset is unique owing to the extreme crystal packing similarity of all 19 crystal forms. This fact makes the evaluation of structure–property relations significantly easier and more precise since the differences in the crystal lattice arrangement are close to negligible. Properties of the guest molecules used here can be directly correlated with the macroscopic properties of the corresponding multicomponent forms. Interestingly, a considerable correlation was found between the intrinsic dissolution rate of the multicomponent forms and their solubility, as well as the solubility of their guest molecules in the dissolution medium. The latter is of particular interest as it can aid in the design of multicomponent forms with tuned properties.

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Naftopidil Molecular Salts with Improved Dissolution and Permeation

Cited by 26 publications

References 32 publications

Recent Advances in Pharmaceutical Cocrystals: From Bench to Market

Recent Advances in Pharmaceutical Cocrystals: From Bench to Market

Tuning Diffusion Permeability of an Anti-Retroviral Drug, Emtricitabine, via Multicomponent Crystallizations

Structure–property relations of a unique and systematic dataset of 19 isostructural multicomponent apremilast forms

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