Effects of Ball-Milling and Cryomilling on Sulfamerazine Polymorphs: A Quantitative Study

MacFhionnghaile, Pól; Hu, Yun; Gniado, Katarzyna; Curran, Sinéad; McArdle, Patrick; Erxleben, Andrea

doi:10.1002/jps.23978

Cited by 31 publications

(40 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cryomilling holds the sample at a temperature below 0 o C, which helps to prevent crystallization of the sample during milling. 48 As shown in Figure 4, following cryomilling CIP still had some residual crystallinity. The four most prominent peaks of the CIP zwitterion are still present in the PXRD of the cryomilled sample; however they are less intense than those obtained with the drug milled at room temperature.…”

Section: Cryomillingmentioning

confidence: 94%

Two Faces of Ciprofloxacin: Investigation of Proton Transfer in Solid State Transformations

Mesallati

Mugheirbi

Tajber

2016

Crystal Growth & Design

View full text Add to dashboard Cite

Ciprofloxacin (CIP) can exist in two different forms: the zwitterion and the unionized form. While the crystal structure of each has been described independently, the ability of CIP to transform from one to the other in the solid state has not been described. The crystal structures of unionized and zwitterionic CIP were therefore compared using computational methods, including their packing arrangement, hydrogen bonding, packing energy, intermolecular potentials and HOMO/LUMO energy gap. The pure amorphous form of CIP has also never been prepared or studied. Ball milling, cryomilling and spray drying were used in this study to prepare partially and fully amorphous CIP for the first time. The physical characteristics were examined by PXRD, FTIR and DSC. CIP proved to be very difficult to amorphize, and only spray drying in pure water resulted in a fully amorphous product. It was discovered that while most processing methods resulted in the more stable zwitterionic form of the drug, spray drying in an ethanol/water mixture produced the unionized form. The zwitterion was found to convert to the unionized form upon heating to its melting point, whereas the reverse transformation occurred when unionized CIP was exposed to high humidity. This study thus provides insight into the proton transfer which can occur in a zwitterionic drug in the solid state, and the resultant changes to its crystal structure. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3 Abstract Ciprofloxacin (CIP) can exist in two different forms: the zwitterion and the unionized form.While the crystal structure of each has been described independently, the ability of CIP to transform from one to the other in the solid state has not been described. The crystal structures of unionized and zwitterionic CIP were therefore compared using computational methods, including their packing arrangement, hydrogen bonding, packing energy, intermolecular potentials and HOMO/LUMO energy gap. The pure amorphous form of this drug has also never been prepared or studied. Ball milling, cryomilling and spray drying were used in this study to prepare partially and fully amorphous CIP for the first time. The physical characteristics, and in particular ionization state, of these samples were examined by PXRD, FTIR and DSC. Analysis of the crystal packing of unionized and zwitterionic CIP revealed that the presence of ionic interactions between the charged groups of the latter results in a denser and more stable crystal lattice. A greater HOMO/LUMO energy gap was also calculated for this sample, confirming its lower reactivity. CIP proved to be very difficult to amo...

show abstract

Section: Cryomillingmentioning

confidence: 94%

Two Faces of Ciprofloxacin: Investigation of Proton Transfer in Solid State Transformations

Mesallati

Mugheirbi

Tajber

2016

Crystal Growth & Design

View full text Add to dashboard Cite

show abstract

“…Co-amorphous SMZ/CA was prepared by cryomilling an equimolar mixture of SMZ and CA and characterized by XRPD as previously described by us (MacFhionnghaile et al, 2014). Co-amorphous SMZ/DA and SMZ/NaTC were obtained in the same way in the present study.…”

Section: Preparation and Characterization Of The Co-amorphous Systemsmentioning

confidence: 99%

“…We have recently studied the milling-induced amorphization of the model API sulfamerazine (SMZ) and demonstrated that co-milling with multifunctional carboxylic acids such as citric acid (CA) can increase the stability of the amorphous phase under ambient conditions from a few hours for the drug alone to several weeks (MacFhionnghaile et al, 2014). In continuation of this work we now report a detailed study of the dissolution behavior of three selected co-amorphous SMZ/carboxylic acid co-former systems, namely SMZ/DA, SMZ/CA and SMZ/NaTC (DA = deoxycholic acid, NaTC = sodium taurocholate, Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

The influence of co-formers on the dissolution rates of co-amorphous sulfamerazine/excipient systems

Gniado

Löbmann

Erxleben

2016

International Journal of Pharmaceutics

Self Cite

View full text Add to dashboard Cite

A comprehensive study on the dissolution properties of three co-amorphous sulfamerazine/excipient systems, namely sulfamerazine/deoxycholic acid, sulfamerazine/citric acid and sulfamerazine/sodium taurocholate (SMZ/DA, SMZ/CA and SMZ/NaTC; 1:1 molar ratio), is reported. While all three co-formers stabilize the amorphous state during storage, only coamorphization with NaTC provides a dissolution advantage over crystalline SMZ and the reasons for this were analyzed. In the case of SMZ/DA extensive gelation of DA protects the amorphous phase from crystallization upon contact with buffer, but at the same time prevents the release of SMZ into solution. Disk dissolution studies showed an improved dissolution behavior of SMZ/CA compared to crystalline SMZ. However, enhanced dissolution properties were not seen in powder dissolution testing due to poor dispersibility. Co-amorphization of SMZ and NaTC resulted in a significant increase in dissolution rate, both in powder and disk dissolution studies.

show abstract

“…Mechanochemistry, due to its non-equilibrium nature, is often employed to produce polymorphs 6 and co-crystals 53 Co-milled 1 and g (HP) in a 1:1 ratio results in a new XRPD pattern ( Figure S13, SI) suggesting the formation of a new co-crystalline adduct. This is further supported by the thermal analysis ( Figure S14, SI) where the material shows an endothermic peak at 187 °C, followed by melting at 202 °C.…”

Section: Ball Millingmentioning

confidence: 99%

Tailoring Cocrystal and Salt Formation and Controlling the Crystal Habit of Diflunisal

Pallipurath

Civati

Eziashi

et al. 2016

Crystal Growth & Design

Self Cite

View full text Add to dashboard Cite

Crystal habit modification of the drug diflunisal that normally grows into extremely thin, long needles has been achieved by breaking the stacking effect with the help of co-formers. Eight new co-crystals are reported, along with three crystal structures. In all cases, ortho F disorder, often a feature in diflunisal structures was absent due to the presence of CH…F interactions. Co-milling diflunisal with oxalic acid produced 1:1 and 2:1 co-crystals. In contrast, in solution crystallisation oxalic acid played the role of an additive resulting in the crystallisation of diflunisal form I rather than form III. To rationalize co-crystal formation a statistical analysis of the CCDC data base for aromatic o-hydroxy carboxylic acids was carried out. All co-crystals of o-hydroxy carboxylic acids with the COOH dimer motif have an electron-withdrawing group on one of the acids. COOH…Nar motifs are formed preferentially over carboxylic homo-dimers in the presence of an Nar co-former. AbstractCrystal habit modification of the drug diflunisal that normally grows into extremely thin, long needles has been achieved by breaking the stacking effect with the help of co-formers. Eight new co-crystals are reported, along with three crystal structures. In all cases, ortho F disorder, often a feature in diflunisal structures was absent due to the presence of CH…F interactions. Co-milling diflunisal with oxalic acid produced 1:1 and 2:1 co-crystals. In contrast, in solution crystallisation oxalic acid played the role of an additive resulting in the crystallisation of diflunisal form I rather than form III. To rationalize co-crystal formation a statistical analysis of the CCDC data base for aromatic o-hydroxy carboxylic acids was carried out. All co-crystals of o-hydroxy carboxylic acids with the COOH dimer motif have an electron-withdrawing group on one of the acids. COOH…Nar motifs are formed preferentially over carboxylic homo-dimers in the presence of an Nar co-former.

show abstract

Effects of Ball-Milling and Cryomilling on Sulfamerazine Polymorphs: A Quantitative Study

Cited by 31 publications

References 84 publications

Two Faces of Ciprofloxacin: Investigation of Proton Transfer in Solid State Transformations

Two Faces of Ciprofloxacin: Investigation of Proton Transfer in Solid State Transformations

The influence of co-formers on the dissolution rates of co-amorphous sulfamerazine/excipient systems

Tailoring Cocrystal and Salt Formation and Controlling the Crystal Habit of Diflunisal

Contact Info

Product

Resources

About