Correlation between in vitro release from topical delivery vehicles and microbicidal activity of triclosan.

This study reports the formulation, stability, in vitro release and microbicidal activity of a cream, emulsion, foot gel, cover stick and after sun spray containing triclosan. Triclosan is a broad-spectrum antimicrobial agent with activity against a wide range of both gram-negative and gram-positive bacteria that has found increasing popular use in personal care products. These products were stable for up to 3 months when stored at 5, 25, and 40 degrees C. Antimicrobial zone inhibition tests showed that that was a liner relationship, R2 > 0.92, between the release of triclosan from these products and the size of the inhibition zones. This means the in vitro/in vivo correlation for these products was good and that release studies can be used to predict the antimicrobial activity of triclosan.

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.

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.

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.

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.

Preformulation stability screening of ivermectin with non-ionic emulsion excipients.

As an important and complementary step during a preformulation study differential scanning calorimetry (DSC) and high-pressure liquid chromatography (HPLC) were used to determine the compatibility between ivermectin and commonly used excipients for preparing non-ionic emulsions. Ivermectin was found to exhibit interactions with 21 excipients, while it was compatible with 25 excipients. HPLC showed a significant decrease in drug amount +20%, when substances interacted with invermectin.

A study of the changes during heating of paracetamol.

The orthorhombic form of paracetamol has been shown to exhibit greater compressibility and faster dissolution than the monoclinic form. The orthorhombic form is produced by melting of monoclinic crystals of paracetamol followed by cooling at specific rates. Cooling rate, although a very important factor, is not the only factor influencing the formation of either of the two morphs. To study the cooling rate required for production of form II, paracetamol samples were melted in a differential scanning calorimeter, cooled at three specific rates, and melted again. In all of the samples, cooling resulted in the glassy form followed by recrystallization and the melting of form II. On the hot-stage microscope both forms were produced in one sample. Standardizing conditions for prediction of the resulting form remains a problem. There seems to be a great deal of overlap of the two forms' transition phases, which would make it difficult to force the crystallization of one form by keeping the solution or melt at a specific temperature. The thermal behavior of paracetamol during the heating and cooling phases must be understood in order to manipulate the process. A video camera mounted on a hot-stage microscope was used to follow the changes during heating and cooling of both forms. Nucleation, crystal growth, habit transformation, sublimation, and the final melt are shown on snap shots taken from the video.

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.

Solid-phase extraction and HPLC determination of levamisole hydrochloride in sheep plasma.

The anthelmintic, levamisole, was determined in sheep plasma by means of ion-pair solid-phase extraction (SPE) and reverse-phase liquid chromatography. The SPE columns were conditioned with 2 ml of methanol followed by 1 ml of octane sulphonic-acid buffer. After sample application, the columns were washed with 2 ml of the same buffer, followed by elution with 90/10 acetonitrile:buffer. A phenyl reverse-phase column (Spherisorb S5 Phenyl, 250 x 4.6 mm) was used with a mobile phase of acetonitrile: 0.005 M of octane sulphonic-acid sodium salt and 0.2% triethylamine in water, pH 3.5, 38/62. Extraction recoveries of 89-94% were achieved over the range from 100-3750 ng/ml. Accuracy and precision were better than 96% and 2.6%, respectively, over said range, with a limit of quantitation of 50 ng/ ml.

A comparison of haemodynamic and vasoconstrictory responses in sheep with a toxic fraction from Pachystigma pygmaeum and with the plant material.

ST-segment changes in the ECG, which are an indication of acute myocardial ischaemia, are obtained when a small quantity of an extract from dried Pachystigma pygmaeum is injected intravenously in sheep. When the fraction was injected subcutaneously, animals reached a crisis after about 5 h, with low values of stroke volumes and high values for pulmonary arterial pressures, pulmonary vascular resistances and heart rates. The haemodynamic changes are an indication of the development of pump failure of the heart. In sheep, injected subcutaneously with the toxic fraction, as well as for sheep dosed with plant material through rumen fistula, increased serum levels for thromboxane and increased or decreased levels for prostacycline were observed. The experimental results are interpreted as being an indication that these prostaglandines may be involved in the development of gousiekte by impeding cardiopulmonary function as a result of coronary and pulmonary vasoconstriction. The sudden death observed in some gousiekte sheep may be due to myocardial ischaemia and associated arrhythmias.

Physical and structural comparison of oxyphenbutazone monohydrate and anhydrate.

Two crystal forms of oxyphenbutazone (a monohydrate and an anhydrate) were prepared by recrystallization. The forms were characterized by means of differential scanning calorimetry, thermogravimetry, infrared spectrophotometry, X-ray powder diffraction patterns, thermomicroscopy, scanning electron microscopy, as well as powder and intrinsic dissolution rates. The crystal structure of the anhydrate has been elucidated and compared with that of the monohydrate.

Physical characterization of the methanol solvate of urapidil.

The methanol solvate of urapidil was prepared and characterized by means of differential scanning calorimetry, thermogravimetric analysis, infrared spectroscopy, X-ray powder diffraction, intrinsic dissolution rate, and solution calorimetry. The stoichiometry of the urapidil:methanol solvate was found to be 1:1. The crystal and molecular structures were determined from three-dimensional X-ray data. The stability of the solvate under different storage conditions was also determined.

Physical characterization of two oxyphenbutazone pseudopolymorphs.

Two pseudopolymorphic forms of oxyphenbutazone, a benzene solvate (Solvate B) and a cyclohexane solvate (Solvate C), were prepared by recrystallization from benzene and cyclohexane, respectively. The forms were characterized by means of differential scanning calorimetry, thermogravimetry, infrared spectrophotometry, X-ray powder diffraction, and thermomicroscopy, as well as powder and intrinsic dissolution rates. The dissolution rates of the two pseudopolymorphs were shown to be superior to those of the anhydrate, hemihydrate, and monohydrate which were previously reported. A brief stability report is included.

Physical characterization of the hydrates of urapidil.

Three hydrates of urapidil were prepared and characterized by means of differential scanning calorimetry, thermogravimetric analysis, infrared spectroscopy, X-ray powder diffraction, intrinsic dissolution rates, and solution calorimetry. The stoichiometry of the urapidil hydrates was found to be 1:5, 1:3, and 1:1 (urapidil:water). The crystal and molecular structures of urapidil pentahydrate were determined from three-dimensional X-ray data. The stability of the pentahydrate and monohydrate under different storage conditions was also determined.

Physicochemical properties and X-ray structural studies of the trigonal polymorph of carbamazepine.

The trigonal polymorph of carbamazepine (alpha-carbamazepine) was obtained by crystallization from a number of solvents. It was characterized by means of differential scanning calorimetry, thermogravimetric analysis, infrared spectroscopy, X-ray power diffraction, thermal microscopy, and powder and intrinsic dissolution rates. The crystal and molecular structures were determined by single-crystal, three-dimensional X-ray analysis. A comparison is drawn between the physicochemical properties of the monoclinic (beta) and trigonal (alpha) forms. Structural features of carbamazepine occurring in these forms and in the acetone solvate are compared. Substantial differences were detected between the two polymorphic forms with regard to infrared and differential scanning calorimetry data, thermomicroscopical behavior, morphology, and molecular conformation.

Effects of an oats fibre tablet and wheat bran in healthy volunteers.

The daily intake of total dietary fibre of a group of 18 healthy volunteers was raised from a mean of 22.1 g to 32 g by supplementing their diet with either 23 g wheat bran or 15 g oats fibre tablets in a cross-over design for two 3-week periods with a wash-out period of 4 weeks in between. Both fibre supplements improved mean glucose tolerance, although not significantly. During the first period, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and very-low-density lipoprotein cholesterol were significantly lowered by both fibre preparations. During the second period significant reductions in TC and LDL-C were obtained only in the group taking the oats fibre tablets. This could probably be explained as an effect of the gel-forming fibre components in oats fibre. High-density lipoprotein cholesterol concentrations remained unchanged. The oats fibre tablet also proved easier to take and caused fewer side-effects. This study shows that if dietary fibre concentrates are used to increase fibre intake in Western societies, better results will probably be obtained by using a dietary fibre concentrate or mixture of concentrates that contain both soluble and insoluble components.

Physical characterization of solid forms of urapidil.

Polymorphic forms of urapidil were prepared by various techniques. Three polymorphic forms were identified and their solid-state properties were characterized by thermal behaviour, X-ray powder diffraction, IR spectra, intrinsic dissolution rates, solution calorimetry and scanning electron microscopy. Solution calorimetry was used to determine each polymorph in mixtures of Forms I and II, with a reproducibility of +/-3%. The stability of the three polymorphic forms was followed over a period of three months under different conditions and it was concluded that Forms I, II and III of urapidil were enantiotropic.