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W Liebenberg

Publications and source records attributed to W Liebenberg.

At least 19 recordsLinked to original sources
PubMed2003

Developing a discriminating dissolution test for three mebendazole polymorphs based on solubility differences.

Mebendazole, a broad spectrum anthelmintic drug, is practically insoluble in water and exists in three polymorphic forms, A, B, and C, of which C is pharmaceutically favoured. Since the dissolution of drugs from solid oral dosage forms can depend on the crystal form of the drug an attempt should be made while developing dissolution tests to set test parameters that are sensitive to changes in the crystal form. USP 24 describes 0.1 M hydrochloric acid containing 1.0% sodium lauryl sulphate (SLS) as the dissolution medium for mebendazole tablets. Results showed that the high concentration of sodium lauryl sulphate in the USP dissolution medium does not allow the use of this test to distinguish between the solubility differences of the three mebendazole polymorphs. By decreasing the amount of sodium lauryl sulphate in the dissolution medium clear differences in the dissolution rates of the three forms were observed. The most discriminating medium was 0.1 M HCl, containing no sodium lauryl sulphate.

Algorithms↗
PubMed2001

Characterization of the solubility and dissolution properties of several new rifampicin polymorphs, solvates, and hydrates.

Based on reports that tuberculosis is on the increase, this investigation into the physicochemical properties of rifampicin when recrystallized from various solvent systems was undertaken. Rifampicin is an essential component of the currently recommended regimen for treating tuberculosis, although relatively little is known about its solubility and dissolution behavior in relation to its solid-state properties. A rifampicin monohydrate, a rifampicin dihydrate, two amorphous forms, a 1:1 rifampicin:acetone solvate, and a 1:2 rifampicin:2-pyrrolidone solvate were isolated and characterized using spectral, thermal, and solubility measurements. The crystal forms were relatively unstable because except for the 2-pyrrolidone solvate, all the hydrated or solvated materials changed to amorphous forms after desolvation. Fourier transform infrared (FTIR) analysis confirmed the favorable three-dimensional organization of the pharmacophore to ensure antibacterial activity in all the crystal forms except the 2-pyrrolidone solvate. In the 2-pyrrolidone solvate, the strong IR signals of 2-pyrrolidone interfered with the vibrations of the ansa group. The 2-pyrrolidone solvate was the most soluble in phosphate buffer at pH 7.4. This solvate also had the highest solubility (1.58 mg/ml) and the fastest dissolution in water. In 0.1 M HCl, the dihydrate dissolved the quickest. A X-ray amorphous form (amorph II) was the least soluble and had the slowest dissolution rate because the powder was poorly wettable and very electrostatic.

Antibiotics, Antitubercular↗
PubMed2000

Dissolution properties of piroxicam powders and capsules as a function of particle size and the agglomeration of powders.

The poor dissolution characteristics of relatively insoluble drugs have long been a problem to the pharmaceutical industry. An example is piroxicam, a highly potent anti-inflammatory agent. In many countries, a large number of generic piroxicam products are available to the prescriber. The aim of this study was to investigate the cause of the dissolution problems experienced by manufacturers of generic piroxicam capsules. Two raw material batches and the dissolution properties of several piroxicam capsules were studied. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) results showed that the two raw material samples were identical with respect to polymorphic modification. The particles of powder 1 were smaller than those of powder 2, but the dissolution of powder 1 was much slower than that of powder 2. The dissolution results for the capsules showed a marked difference among different brands, with capsule C not meeting the USP tolerance. Adding surfactant to the dissolution medium increased the dissolution of both powder 1 and capsule C. Failure of powder 1 or capsule C to meet USP dissolution criteria could result in differences in product efficacy, as well as in potential side effects. Such observations should be taken into account along with other relevant considerations when decisions regarding the generic substitution of oral piroxicam products are made.

Administration, Oral↗
PubMed2000

Solubility and dissolution properties of generic rifampicin raw materials.

Rifampicin shows polymorphism; therefore, it is necessary to select a suitable crystal form at an early stage of development to ensure optimum solubility and dissolution rates. This study was an investigation into the crystal properties of several rifampicin raw materials currently being used by manufacturers of generic rifampicin raw materials in South Africa. Powders were characterized by X-ray diffraction (XRD), infrared (IR) spectroscopy, and differential scanning calorimetry (DSC). The solubility in water and dissolution properties in water, buffer pH 7.4 and 0.1 M HCl, were also measured. The main difference between the powders was the amorphous content. XRD, IR, and DSC methods could detect the presence of amorphous rifampicin. In contrast to expectations, an increase in amorphous content significantly reduced the dissolution rate of the powders in water and buffer pH 7.4. This behavior was attributed to the electrostatic properties of the very fine particles in the amorphous powders. The results of this study showed that the physical properties of rifampicin raw materials varied not only among manufacturers, but also among batches from the same manufacturer.

Antibiotics, Antitubercular↗
PubMed2000

Characterization of zopiclone crystal forms found among generic raw materials.

This paper deals with the occurrence of polymorphs and pseudopolymorphs and their effect on the solid-state properties of zopiclone, a poorly water soluble nondiazepine sedative and hypnotic drug. X-ray powder diffraction (XRPD), infrared spectroscopy (IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), particle size analysis, dissolution studies, and solubility determinations were used to characterize the zopiclone raw materials. An anhydrated form, a dihydrated form, and a mixture of these two crystal forms were found and characterized among the zopiclone powders.

Azabicyclo Compounds↗
PubMed2000

Effects of derivatives of NGP 1-01, a putative calcium channel antagonist, on electrically stimulated guinea-pig papillary muscle.

In earlier work we have reported calcium antagonistic properties for the polycyclic compound NGP 1-01. We now have derivatized NGP 1-01 by side-chain substitution to obtain ten novel aromatic and aliphatic imino-keto and amino-ether compounds. Electrophysiological tests were conducted on these compounds using isolated guinea-pig papillary muscle preparations to record calcium-mediated (slow) action potentials (APs). The lipophilicities of the compounds, expressed as chromatographically determined RM values, were measured and the molecular surface areas calculated. Several derivatives showed increased activity compared with NGP 1-01. All compounds with aromatic side-chains (benzyl, phenethyl, phenylpropyl) were active (concentrations required for complete suppression of the AP varied between 1 x 10(-5) M and 5 x 10(-5) M) and compounds with shorter (methyl, butyl) aliphatic side-chains were inactive whilst activity increased dramatically in those compounds with octyl side-chains. Lipophilicity and calculated molecular volumes correlated linearly and bulkier, more lipophilic molecules had increasing activities in the electrophysiological assay. We therefore conclude that bulky substituents on the nitrogen atom increase calcium antagonistic activity in this series of compounds.

Animals↗
PubMed1999

The dissolution and complexing properties of ibuprofen and ketoprofen when mixed with N-methylglucamine.

The objectives of this study were to improve the aqueous dissolution properties of the poorly soluble nonsteroidal anti-inflammatory drugs ibuprofen and ketoprofen and to explore the use of N-methylglucamine (meglumine) to enhance the dissolution properties of poorly water-soluble drug powders. Changes in both differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) results indicate that possibly complexes were produced between ibuprofen and N-methylglucamine. Similar changes were not observed for equivalent ketoprofen and N-methylglucamine mixtures. The results of solubility and dissolution studies in water at 25 degrees C and 37 degrees C showed that N-methylglucamine, in mixtures and coprecipitates, increased the solubility, intrinsic dissolution, and powder dissolution of ketoprofen and ibuprofen. N-Methylglucamine significantly improved the solubility and dissolution properties of both ibuprofen and ketoprofen even when DSC and XRD behavior did not indicate the formation of complexes.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

The effect of polymorphism on powder compaction and dissolution properties of chemically equivalent oxytetracycline hydrochloride powders.

In South Africa, oxytetracycline is identified as an essential drug; many generic products are on the market, and many more are being developed. In this study, six oxytetracycline hydrochloride powders were obtained randomly from manufacturers, and suppliers were compared. It was found that compliance to a pharmacopoeial monograph was insufficient to ensure the optimum dissolution performance of a simple tablet formulation. Comparative physicochemical raw material analysis showed no major differences with regard to differential scanning calorimetry (DSC), infrared (IR) spectroscopy, powder dissolution, and particle size. However, the samples could be divided into two distinct types with respect to X-ray powder diffraction (XRD) and thus polymorphism. The two polymorphic forms had different dissolution properties in water or 0.1 N hydrochloride acid. This difference became substantial when the dissolution from tablets was compared. The powders containing form A were less soluble than that containing form B.

Calorimetry, Differential Scanning↗
PubMed1998

Identification of the mebendazole polymorphic form present in raw materials and tablets available in South Africa.

A preformulation study of four different raw materials of mebendazole showed that three samples were polymorph C and the other polymorph A, or a mixture of form A and B. X-ray powder diffractometry and infrared spectroscopy indicated that this powder could be form B, but powder dissolution, for which a much slower dissolution was obtained, suggests polymorph A. Literature prescribes the use of polymorph C pharmaceutically, but generic manufacturers should be aware that forms other than C are still available on the market. The four mebendazole tablets currently available in South Africa were also tested and it was found that all of them contained polymorph C.

Calorimetry, Differential Scanning↗
PubMed1997

Dental hygiene.

Explore the source record for details and available documents.

Dental Hygienists↗
PubMed1996

The biological activity of two symmetric amine derivatives of the cis-syn-cis triquinane system.

N-benzyl-3,11-azatricyclo[6.3.0.0]undecane and N-octyl-3,11-azatricyclo[6.3.0.0]undecane, two triquinane compounds containing an endocyclic nitrogen atom and differing side-chains, were synthesized by thermal 2 + 2 cycloreversion from the symmetric cage compound pentacyclo[5.4.0.0.0.0]undecane-8,11-dione. The conformation of the cyclic system showed close similarity with the conformation of the hydrate of 4-methyltricyclo[6.3.0.0]undeca-3,11-dione. Both N-benzyl-3,11-azatricyclo[6.3.0.0]undecane and N-octyl-3,11-azatricyclo[6.3.0.0]undecane showed similar suppressant activity on the Ca2+ action potential of guinea-pig papillary muscle--the benzyl (aromatic) derivative fully suppressed the action potential (AP) whilst the aliphatic (octyl) derivative suppressed the AP to about 50% at the same dosages. Similarly, both these compounds (irreversibly) suppressed the chronotropy of spontaneously contracting guinea-pig atria by approximately 30% at concentrations of 1 x 10(-5) M or more.

Action Potentials↗