Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

Heinz, Andreas; Strachan, Clare J.; Gordon, Keith C.; Rades, Thomas

doi:10.1211/jpp/61.08.0001

Cited by 72 publications

(60 citation statements)

References 145 publications

(256 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…51 The asymmetric and symmetric vibrations of the COOgroup are far weaker than in the crystalline drug; however amorphous solids are known to exhibit broader bands of lower intensity than their crystalline form. 52 These samples also contain a minor amount of unionized CIP, as a small peak can be seen in their spectra at around 1720 cm -…”

Section: Solid State Fourier Transform Infrared Spectroscopymentioning

confidence: 99%

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: Solid State Fourier Transform Infrared Spectroscopymentioning

confidence: 99%

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

“…Knowledge of the solid state of the API during processing and storage is of the highest importance to assure a safe drug product. Changes in solid state can influence the chemical and physical properties of API's, resulting in different processability (compressibility and powder flow), but also solubility, stability and bioavailability [24]. Norvir, an anti-HIV medicine, was already on the market when in 1998 a polymorphic transformation to a less soluble form of ritonavir was detected [25].…”

Section: Gewijzigde Veldcodementioning

confidence: 99%

Real-time assessment of critical quality attributes of a continuous granulation process

Fonteyne

Vercruysse

Díaz

et al. 2011

Pharmaceutical Development and Technology

104

View full text Add to dashboard Cite

There exists the intention to shift pharmaceutical manufacturing of solid dosage forms from traditional batch production towards continuous production. The currently applied conventional quality control systems, based on sampling and time-consuming off-line analyses in analytical laboratories, would annul the advantages of continuous processing. It is clear that real-time quality assessment and control is indispensable for continuous production. This manuscript evaluates strengths and weaknesses of several complementary Process Analytical Technology (PAT) tools implemented in a continuous wet granulation process, which is part of a fully continuous from powder-to-tablet production line. The use of Raman and NIR spectroscopy and a particle size distribution analyzer is evaluated for the real-time monitoring of critical parameters during the continuous wet agglomeration of an anhydrous theophylline -lactose blend. The solid state characteristics and particle size of the granules were analyzed in real-time and the critical process parameters influencing these granule characteristics were identified. The temperature of the granulator barrel, the amount of granulation liquid added and, to a lesser extent, the powder feed rate were the parameters influencing the solid state of the active pharmaceutical ingredient (API). A higher barrel temperature and a higher powder feed rate, resulted in larger granules.

show abstract

“…[4][5][6][7][8][9][10] As examples, the meta-stable crystalline form of carbamazepine is transformed into a stable form during granulation and drying, 11) and anhydrous caffeine and chlorproamide are transformed during grinding and compressing.…”

Section: )mentioning

confidence: 99%

The Effect of Compaction Force on the Transition to Hydrate of Anhydrous Aripiprazole

T¹,

Taniguchi²,

Nakata³

2018

Chem. Pharm. Bull.

View full text Add to dashboard Cite

Aripiprazole (APZ) is used to treat schizophrenia and is administered as a tablet containing the anhydrous form of APZ. In this study, the effect of compaction force on the crystal form transition was investigated. The crystalline state was observed by X-ray diffraction (XRD). APZ Anhydrous Form II was compacted into tablets. The XRD intensity of anhydrous APZ became lower with higher compressive force. The degree of crystallinity decreased with the compaction force. The powder and the compacted tablets of anhydrous APZ were stored for one week under 60°C and 75% relative humidity. The powder showed no crystal form transition after storage. For the tablets, however, XRD peaks of APZ hydrate were observed after storage. The tablets compacted with higher force showed the higher XRD diffraction intensity of hydrate form. We concluded that the crystallinity reduction of APZ Anhydrous Form II by compaction caused and accelerated the transition to hydrate under high temperature and humidity conditions. In order to manufacture crystallographically stable tablets containing anhydrous APZ, it is important to prevent this crystallinity reduction during compaction.Key words aripiprazole; crystal transition; hydration; compaction; tablet Many active pharmaceutical ingredient (API) bulk powders have various solid states, such as polymorphic forms, solvates, and amorphous forms. 1)The physicochemical properties, chemical stability and dissolution behaviors of the meta-stable crystalline forms and amorphous forms of poorly water-soluble APIs in pharmaceutical preparations are significantly affected by storage conditions including temperature and humidity. Therefore, changes in the crystalline and amorphous forms during the manufacturing process may affect the bioavailability of the pharmaceutical products as a result of changes to their physical properties (melting point, solubility, etc.), chemical stability and absorbability in the gastrointestinal tract.2,3) The crystallization process of metastable bulk drug powder is important for the quality assurance of drugs, depending on the bioavailability of the pharmaceutical formulation. [4][5][6][7][8][9][10] As examples, the meta-stable crystalline form of carbamazepine is transformed into a stable form during granulation and drying, 11) and anhydrous caffeine and chlorproamide are transformed during grinding and compressing.12,13) The crystallinity of SX3288 decreases by grinding and compressing, leading to reduced chemical stability.14)The amorphous state is a state lacking regularity with a wide range of orders and orientations of the molecule. Since an amorphous solid with high chemical potential is more easily soluble in water than the crystalline solid, some poorly water-soluble pharmaceuticals have been used in an amorphous state, with the expectation of improving the dissolution rate in water. 15,16) However, the amorphous state has the potential to change to a more stable crystalline state by adsorbing various solvent vapors during the storage of pharmaceuticals. 17)Ari...

show abstract

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

Cited by 72 publications

References 145 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

Real-time assessment of critical quality attributes of a continuous granulation process

The Effect of Compaction Force on the Transition to Hydrate of Anhydrous Aripiprazole

Contact Info

Product

Resources

About