Chloroquine diphosphate

Differential thermal analysis proved to be a powerful tool in the study of compound polymorphism, and in the characterization of solvate species of drug compounds. In addition, it can be used to deduce the ability of polymorphs to thermally interconvert, thus establishing the system to be monotropic or enantiotropic in nature. For instance, form I of chloroquine diphosphate melts at 216°C, while form II melts at 196°C [18]. The DTA thermogram of form I consists of a simple endotherm, while the thermogram of form II is complicated (see Fig. 4). The first endotherm at 196°C is associated with the melting of form II, but this is immediately followed by an exotherm corresponding to the crystallization of form I. This species is then observed to melt at 216°C, establishing it as the thermodynamically more stable form at the elevated temperature. 

Fig. 4 DTA thermogram of chloroquine diphosphate, form II, illustrating the melting endotherm of form II (196°C), recrystallization to form I, and final melting endotherm attributable to the converted form I (216°C). (Data adapted from Ref. 18.)...

Chloroquine diphosphate- none PDMSa Burst, than fairly constant rates (4 months) [1]... 

Figure 7.3.1.7 A 13C-decoupled HMQC spectrum of 54 mM chloroquine diphosphate in D2O acquired with an inverse detection microcoil probe. The 740-nl F0bs contained 40 nmol (13 jig) of chloroquine. The data, 32 transients per slice, 1024 x 128 (x2, hypercomplex) points, were acquired in 3.6h. The data were zero-filled to 256 points in the 13C dimension. A 40° shifted sinebell function was applied, followed by Gaussian multiplication prior to Fourier transformation...

Nord K, Andersen H, Tormesen HH. Photoreactivity of biologically active compounds. XII. PhotostabUity of polymorphic modifications of chloroquine diphosphate. Drug Stab 1997 1 243-248. 

The simplest and most straightforward application of thermal analysis is concerned with studies of the relative stability of polymorphic forms. For example, DTA thermograms enabled the deduction that one commercially available form of chloroquine diphosphate was phase pure, while another consisted of a mixture of two polymorphs. DTA analysis was used to demonstrate that in spite of the fact that different crystal habits of sulfamethazine could be obtained, these in fact consisted of the same anhydrous poly-morph.f In a study aimed at profiling the dissolution behavior of the three polymorphs and five solvates of spironlactone, DTA analysis was used in conjunction with powder X-ray diffraction to establish the character of the various materials. ... 

Aromoline was screened for in vitro antimalarial properties using a multi-drug resistant (Kl) strain of Plasmodium falciparum. The screen detected the inhibition of incorporation of [3H]-hypoxanthine into P. falciparum, and aromoline was characterized by IC 0.67 pg/ml (with 95% confidence intervals of 0.53 - 0.85). The standard antimalarial drug chloroquine diphosphate exhibits IC 0.14 pg/ml (with 95% confidence intervals of 0.12 - 0.16)[177]. 

The transformation from one crystalline form to the other can also occur during the manufacturing processes. Chloroquine diphosphate crystals for example can be obtained anhydrous by storing the hydrate at elevated temperatures. Dehydration is favored by grinding the raw... 

Meinao IM, Sato El, Andrade LE, et al. Controlled trial with chloroquine diphosphate in systemic lupus erythematosus. Lupus 1996 5 237-241. 

Chandra for their help in the work and Walter Reed Army Institute, Washington DC, for kindly providing us chloroquine diphosphate. 

Figure 16.4 Formation of new crystal modifications during processing of chloroquine diphosphate.

The photochemical reduction of Methylene Blue by triethylamine in methanol has been investigated. Photolysis of 3-(3,4-dichlorophenyl)-l,l-dimethylurea (diuron) in aqueous solution containing methanol gives 3-(3-chlorophenyl)-l,l-dimethylurea. The photostabilities of chloroquine diphosphate and mefloquine hydrochloride have been reported and a commentary published on the... 

Dehydration of hydrates can also lead to the formation of unique crystals. Caffeine Form II was prepared by recrystallizing caffeine from water, drying for 8 days at 30°C, and then heating for 4 hours at 80°C [38]. Chloroquine diphosphate 3 1 hydrate was converted to the anhydrous form at temperatures above 188°C [49]. Etoposide Form I (a monohydrate) was found to undergo a dehydration reaction in the temperature range of 85-115°C to yield etoposide Form la. This form could be melted at 198°C and transformed to etoposide Form Ila, which itself melted at 198°C and crystallized to still another polymorph, etoposide Form Ila at 206°C. Etoposide Form Ila was found to melt at 269°C and convert to its hydrated form, etoposide Form n, when exposed to the atmosphere at room temperature. This hydrate was also found to undergo a dehydration reaction at 90-120°C to yield etoposide Form Ila [50]. 

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