Karl-Heinz Frömming

Development of computerised procedures for the characterisation of the tableting properties with eccentric machines: extended Heckel analysis

Heckel plots are a suitable and valuable method for analysis of powder compaction with very small amounts of powder. The determination is based upon a non-linear transformation of compression data and thus the signal errors that might be introduced into the analysis might be enlarged and become critical. The method of determination of true density affects the results dramatically as does the accuracy of the powder height determination. The porosity should be corrected for compression of the solid fraction. The accuracy of the powder height detection is the most demanding parameter. The statements are proven by simulations based on real data and analytic calculation. According to these highly corrected Heckel plots, the shape of the plots during the compression phase gives the information about fragmentation and plasticity and additionally about the time dependency of the compression behaviour within one compression on an eccentric press.

Composition and properties of freeze-dried products of nicotinic acid withβ-cyclodextrin and heptakis (2,6-0-dimethyl)-β-cyclodextrin

The purpose of the study was to examine the formation of inclusion compounds in the freeze-dried products obtained from aqueous solutions of nicotinic acid and β-cyclodextrin (β-CD), or heptakis (2,6-0-dimethyl)-β-cyclodextrin (DIMEB). The molar ratios used were 1:1 and 2:1. In addition two freezing temperatures (−40 and −196°C) and different secondary drying temperatures (+50 and +80°C) were used. Freeze-dried products with β-CD obtained after low temperature freezing are of the same crystallographic structure as seen in a pure inclusion compound prepared by coprecipitation. Amorphous products were formed after fast freezing. The molar ratios of included nicotinic acid in the freeze-dried products vary — dependent on the preparation conditions — between 0.75:1 and 1:1. A factorial design proves that the included drug amount can be increased by enhancement of the amount of nicotinic acid used, by faster freezing, and by the combination of these two factors. The proof of inclusion formation was given by a combination of X-ray diffractography, differential scanning calorimetry, thermogravimetry and thermofractography.The freeze-dried preparations obtained with DIMEB were amorphous mixtures of the two components. No proof for inclusion of the nicotinic acid in the cyclodextrin cavity could be given. Higher (−40°C) or lower (−196°C) freezing temperatures and the running of the secondary drying process could not influence these results. The very low stability constant of the complex and steric reasons are responsible for this behavior.

The inclusion compound of emulsified cetostearyl alcohol withβ-cyclodextrin and a competitive reaction with a hydrocortisone/β-cyclodextrin inclusion compound in an oil-in-water cream

Abstractβ-cyclodextrin can form a solid inclusion compound with emulsified cetostearyl alcohol (ECA) by coprecipitation. This was proved by differential scanning calorimetry (DSC), X-ray diffractometry, IR spectrometry and the determination of the foaming ability according to the German Pharmacopeia (DAB 10) for ECA in the coprecipitate. The DSC result shows that both ingredients, cetostearyl alcohol and cetostearyl sulfate, are included in theβ-CD cavity. The coprecipitate is therefore a mixture of inclusion compounds. ECA as a constituent of Hydrophilic Ointment (DAB 10) can substitute up to 10% hydrocortisone in Aqueous Hydrophilic Ointment(DAB 10) containing 1% HC asβ-CD inclusion compound under the conditions of preparation.

In vitro nitrosation of ephedrine in the presence of cyclodextrins

Abstractβ-, and γ-cyclodextrin and heptakis-2,6-di-O-methyl-β-cyclodextrin enhance the nitrosation rate of l-ephedrine if the nitrosation assay procedure (NAP test) is applied. During this reaction with β-cyclodextrin a solid inclusion compound of β-cyclodextrin andN-nitrosoephedrine precipitates. Solubilities and stabilities of inclusion compounds of the cyclodextrins with ephedrine and nitrosoephedrine, respectively, explain especially the catalytic effects of some cyclodextrins on ephedrine.

Nitrosation of mefenorex in the presence of cyclodextrins

Abstractβ- and γ-Cyclodextrin (CD) and heptakis-2,6-di-O-methyl-β-cyclodextrin (DIMEB) form soluble inclusion compounds with mefenorex (MEF); with α-CD a partial inclusion occurs. No solid inclusion compound could be obtained with the four CDs. β-, γ-CD and DIMEB, but not α-CD, enhance the nitrosation rate of MEF if the nitrosation assay procedure (NAP test) is applied. During this reaction with β- and γ-CD, solid inclusion compounds of the CDs and nitrosomefenorex (NMEF) precipitate.