Cocrystallization with flufenamic acid: comparison of physicochemical properties of two pharmaceutical cocrystals

Aitipamula, Srinivasulu; Wong, Annie B. H.; Chow, Pui Shan; Tan, Reginald B. H.

doi:10.1039/c3ce42182a

Cited by 64 publications

(66 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An O-H···N hydrogen bond involving the carboxylic acid of the FFA and unsaturated N atom of the imidazole ring of TP results in a fourcomponent supramolecular unit. 34 The identity of each powder sample was confirmed by comparison of the measured and predicted PXRD patterns shown in Figure 2. It can be seen that the calculated PXRD patterns were in good agreement with the experimental data for all crystals.…”

Section: Ffa I and Ffa Cocrystals Characterization Morphology Predicmentioning

confidence: 82%

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

et al. 2017

View full text Add to dashboard Cite

Effects of three polymers, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and copolymer of vinyl pyrrolidone/vinyl acetate (PVP-VA), on the dissolution behaviour of the cocrystals of flufenamic acid with theophylline (FFA-TP CO) and nicotinamide (FFA-NIC CO) were investigated at multiple length scales. At the molecular level, the interactions of crystal surfaces with a polymer were analysed by observing etching pattern changes using atomic force microscopy. At the macroscopic scale, dissolution rates of particular faces of a single crystal were determined by measurement of the physical retreat velocities of the faces using optical light microscopy. In the bulk experiments, the FFA concentration in a dissolution medium in the absence or presence of a polymer was measured under both sink and non-sink conditions. It has been found that the dissolution mechanisms of FFA-TP CO are controlled by the defect sites of the crystal surface and by precipitation of the parent drug FFA as individual crystals in the bulk fluid. In contrast, the dissolution mechanisms of FFA-NIC CO are controlled by surface layer removal and by a surface precipitation mechanism, where the parent drug FFA precipitates directly onto the surface of the dissolving cocrystals. Through controlling the dissolution environment by pre-dissolving a polymer, PVP or PVP-VA, which can interact with the crystal surface to alter its dissolution properties, improved solubility and dissolution rates of FFA-TP CO and FFA-NIC CO have been demonstrated.

show abstract

Section: Ffa I and Ffa Cocrystals Characterization Morphology Predicmentioning

confidence: 82%

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In a different study, Aitipamula and coworker reported [88] Figure 24a. The resultant cocrystal shows a better solubility and dissolution rate compared to FFA (Figure 24b).…”

Section: Flufenamic Acid Cocrystalsmentioning

confidence: 92%

“…In a different study, Aitipamula and coworker reported [88] a multidrug cocrystal of FFA with theophylline along with two other coformers-namely, 2-pyridone and 4,4΄-pyridine. The crystal structure contains theophylline dimer between the saturated N of the imidazole ring and one of the carbonyl group forming N-H Figure 24a.…”

Section: Flufenamic Acid Cocrystalsmentioning

confidence: 99%

Drug‑Drug and Drug‑Nutraceutical Cocrystal/Salt as Alternative Medicine for Combination Therapy: A Crystal Engineering Approach

2018

View full text Add to dashboard Cite

The pre-formulation of pharmaceutical cocrystals and salts is a concept of crystal engineering that has emerged as a promising technique for drug development in pharmaceutical industry. Recent introduction of pharmaceutical cocrystals in regulatory guidelines of US Food and Drug Administration (FDA) made them one of the potential alternatives when salt preparation is not feasible. Apart from generally regarded as safe (GRAS) coformers, drug-drug and drug-nutraceutical cocrystals are recent additions to pharmaceutical cocrystal family that have additional health benefits. Indeed, preparation of salt forms is a routine practice to deal with inadequacies associated with the active pharmaceutical ingredient (API) and happens to be a potentially reliable method. Amongst them, drug-drug and drug-nutraceutical cocrystals have drawn significant importance in the recent past as they reduce drug load and cost effects during multiple disease diagnosis. However, one has to be prudent in the selection of drug molecules, the presence of complementary hydrogen bond synthon, disease management during multiple disease therapy, etc. that play important roles in their preparation. That is the reason why drug-drug cocrystals are scarce in the literature compared to pharmaceutical cocrystals containing GRAS coformers and salt forms. Herein, we discuss case studies preferably the reported drug-drug, drug-nutraceutical cocrystals, and a few salts with an emphasis on their role in physicochemical property modulation.

show abstract

“…FFA showed a characteristic peak due to the stretching of secondary amine N-H at 3318 cm −1 . The C = O and C = C vibrational wavenumbers are clear at 1654 cm −1 and 1578 cm −1 , respectively [ 44 , 45 ]. No significant shift in the peaks between FFA and PL were recorded.…”

Section: Resultsmentioning

confidence: 99%

Influence of the microwave technology on solid dispersions of mefenamic acid and flufenamic acid

et al. 2017

View full text Add to dashboard Cite

The present studies were undertaken to develop solvent-free solid dispersions (SDs) for poorly soluble anti-inflammatory drugs mefenamic acid (MA) and flufenamic acid (FFA) in order to enhance their in vitro dissolution rate and in vivo anti-inflammatory effects. The SDs of MA and FFA were prepared using microwaves irradiation (MW) technique. Different carriers such as Pluronic F127® (PL), Eudragit EPO® (EPO), polyethylene glycol 4000 (PEG 4000) and Gelucire 50/13 (GLU) were used for the preparation of SDs. Prepared MW irradiated SDs were characterized physicochemically using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infra-red (FT-IR) spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The physicochemical characteristics and drug release profile of SDs were compared with pure drugs. The results of DSC, TGA, FT-IR, PXRD and SEM showed that SDs were successfully prepared. In vitro dissolution rate of MA and FFA was remarkably enhanced by SDs in comparison with pure MA and FFA. The SDs of MA and FFA prepared using PEG 400 showed higher drug release profile in comparison with those prepared using PL, EPO or GLU. The dissolution efficiency for MA-PEG SD and FFA-PEG SD was obtained as 61.40 and 59.18%, respectively. Optimized SDs were also evaluated for in vivo anti-inflammatory effects in male Wistar rats. The results showed significant % inhibition by MA-PEG (87.74% after 4 h) and FFA-PEG SDs (81.76% after 4 h) in comparison with pure MA (68.09% after 4 h) and pure FFA (55.27% after 4 h) (P<0.05). These results suggested that MW irradiated SDs of MA and FFA could be successfully used for the enhancement of in vitro dissolution rate and in vivo therapeutic efficacy of both drugs.

show abstract

Cocrystallization with flufenamic acid: comparison of physicochemical properties of two pharmaceutical cocrystals

Cited by 64 publications

References 36 publications

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

Drug‑Drug and Drug‑Nutraceutical Cocrystal/Salt as Alternative Medicine for Combination Therapy: A Crystal Engineering Approach

Influence of the microwave technology on solid dispersions of mefenamic acid and flufenamic acid

Contact Info

Product

Resources

About