Interrelation of the dissolution behavior and solid-state features of acetazolamide cocrystals

Arenas-García, Jenniffer I.; Herrera-Ruiz, Dea; Morales‐Rojas, Hugo; Höpfl, Herbert

doi:10.1016/j.ejps.2016.09.025

Cited by 25 publications

(17 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The single crystal structure of BUM has molecules connected via the carboxylic acid dimer homosynthon and N–H···O hydrogen bonds. These intermolecular interactions together with our experience with similar molecules such as furosemide, − acetazolamide, ,, and p -sulfonamide benzoic acid suggested that coformers such as pyridones (2HP, MeHP, OMeHP) and pyridine carboxamides (INA, PAM, and NAM) will result in binary and possibly ternary cocrystals.…”

Section: Resultsmentioning

confidence: 92%

Supramolecular Synthons in Bumetanide Cocrystals and Ternary Products

Allu

Bolla

Tothadi

et al. 2017

Crystal Growth & Design

View full text Add to dashboard Cite

A novel design strategy for cocrystals of the diuretic sulfonamide drug bumetanide (BUM) with carboxamides is reported based on reliable supramolecular synthons. Binary cocrystals of BUM with pyridine carboxamides, pyridones, and cytosine were obtained by solvent-assisted grinding followed by solution crystallization. All cocrystal structures exhibit hydrogen bonding of the coformer with the carboxylic acid group of BUM via heterosynthons which replace the acid homodimer in the drug crystal structure. Pyridones are inserted as N–H···O dimers which are in turn bonded to the acid group of BUM, while the pyridine amide coformers interact via the acid–amide heterosynthon. Cocrystal polymorphs were obtained for bumetanide–isonicotinamide cocrystal structure with the sulfonamide–pyridine and sulfonamide–acid synthons. Careful crystal packing analysis of BUM structure and nine new binary adducts gave an idea for the design ternary cocrystals, and subsequently four new ternary crystalline products were crystallized. Whereas the binary cocrystal structures were confirmed by single crystal diffraction, the ternary combinations were characterized by their unique powder X-ray diffraction patterns as well as by thermal and spectroscopic techniques.

show abstract

Section: Resultsmentioning

confidence: 92%

Supramolecular Synthons in Bumetanide Cocrystals and Ternary Products

Allu

Bolla

Tothadi

et al. 2017

Crystal Growth & Design

View full text Add to dashboard Cite

show abstract

“…On the other hand, it has been proven that addition of theophylline and caffeine contributes to the bioavailability increase of many compounds including salicylic acid . It is also worth mentioning that there are many documented examples of solubility and dissolution behavior enhancement achieved through crystallization of sparingly soluble pharmaceuticals with phenolic acids. ,− Previous work and this study show that the miscibility of the unknown system can be inferred from the similar known cases using miscibility correlation plots (Figures and ), and, therefore, it seems to be possible to predict solubility in a similar manner. Indeed, there is a linear trend between caffeine and theophylline cocrystals (Figure ).…”

Section: Resultsmentioning

confidence: 51%

Applicability of Phenolic Acids as Effective Enhancers of Cocrystal Solubility of Methylxanthines

Przybyłek

Ziółkowska²,

Mroczyńska³

et al. 2017

Crystal Growth & Design

View full text Add to dashboard Cite

Applicability of phenolic acids as potential cocrystal formers for methylxanthine derivatives was analyzed both in terms of cocrystallization probabilities and solubility advantage. The cocrystal formation abilities were evaluated using mixing enthalpy estimated within the conductor like screening model for real solvents (COSMO-RS) framework. The solubility improvement of potential cocrystals was estimated by formulation of the model relating experimental values to predicted solubilities. This enabled for ranking of potential cocrystals formers according to their solubility enhancement potential. According to the calculation results, a highly linear relationship (R 2 = 0.989) was found between estimated theophylline and caffeine cocrystal solubility values. It has been found that many phenolic acids, especially ones with several hydroxyl groups attached to phenyl ring, are the most promising candidates for cocrystallization with caffeine or theophylline. Experimental verification of the proposed protocol for caffeine and theophylline resulted in eight new molecular complexes, which were synthesized via a mechanochemical approach. All new solids were characterized using powder X-ray diffractometry and Fourier transform infrared spectroscopy combined with a attenuated total reflection technique.

show abstract

“…The difference with respect to pure CTD does not correspond to the elimination of all CAF, indicating that probably a chemical reaction among the residues of CTD and CAF occurred. Thus, for CTD-CAF the cocrystal decomposition process is complex and does not initiate just with coformer release, as observed for other pharmaceutical cocrystals [67,68].…”

Section: Analysis By Ir Spectroscopymentioning

confidence: 79%

Tailoring Chlorthalidone Aqueous Solubility by Cocrystallization: Stability and Dissolution Behavior of a Novel Chlorthalidone-Caffeine Cocrystal

et al. 2022

Self Cite

View full text Add to dashboard Cite

A cocrystal of the antihypertensive drug chlorthalidone (CTD) with caffeine (CAF) was obtained (CTD-CAF) by the slurry method, for which a 2:1 stoichiometric ratio was found by powder and single-crystal X-ray diffraction analysis. Cocrystal CTD-CAF showed a supramolecular organization in which CAF molecules are embedded in channels of a 3D network of CTD molecules. The advantage of the cocrystal in comparison to CTD is reflected in a threefold solubility increase and in the dose/solubility ratios, which diminished from near-unit values for D0D to 0.29 for D0CC. Furthermore, dissolution experiments under non-sink conditions showed improved performance of CTD-CAF compared with pure CTD. Subsequent studies showed that CTD-CAF cocrystals transform to CTD form I where CTD precipitation inhibition could be achieved in the presence of pre-dissolved polymer HPMC 80–120 cPs, maintaining supersaturation drug concentrations for at least 180 min. Finally, dissolution experiments under sink conditions unveiled that the CTD-CAF cocrystal induced, in pH-independent manner, faster and more complete CTD dissolution when compared to commercial tablets of CTD. Due to the stability and dissolution behavior of the novel CTD-CAF cocrystal, it could be used to develop solid dosage forms using a lower CTD dose to obtain the same therapeutic response and fewer adverse effects.

show abstract

Interrelation of the dissolution behavior and solid-state features of acetazolamide cocrystals

Cited by 25 publications

References 56 publications

Supramolecular Synthons in Bumetanide Cocrystals and Ternary Products

Supramolecular Synthons in Bumetanide Cocrystals and Ternary Products

Applicability of Phenolic Acids as Effective Enhancers of Cocrystal Solubility of Methylxanthines

Tailoring Chlorthalidone Aqueous Solubility by Cocrystallization: Stability and Dissolution Behavior of a Novel Chlorthalidone-Caffeine Cocrystal

Contact Info

Product

Resources

About