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.

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.

Pharmacological effects of Agapanthus africanus on the isolated rat uterus.

The Agapanthus africanus plant is used by South African traditional healers as a phytomedicine in herbal remedies to treat pregnancy-related ailments and to augment labour. It has already been shown that an aqueous extract of A. africanus causes smooth muscle contractions in the isolated uterus and ileum preparations. In the present study, the effects of an aqueous extract of A. africanus leaves was examined on receptor systems involved in contraction of the uterine smooth muscle in order to determine the mechanism of its pharmacological effect relevant to its ethnic use to augment labour. The extract was tested on the isolated rat uterus preparation. The aqueous extract of A. africanus leaves was found to exhibit agonist activity on uterine muscarinic receptors and to promote the synthesis of prostaglandins in the oestrogenized rat uterus. Some pharmacological justification for the ethnic use of A. africanus as a herbal oxytocic in prolonged labour has been provided.

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.

Antiviral properties of 4-amino-(D3)-trishomocubanes.

Two amino derivatives of (D3)-Trishomocubanes recently synthesized were evaluated for their in vivo and in vitro activities against selected viruses. Both these derivatives exhibited promising in vivo activity against Herpes simplex Type II and Influenza A2/Taiwan, comparable with aciclovir and amantadine, respectively. No in vitro activity was observed for both compounds against Herpes simplex Types I and II and Rhinovirus 1A.

Synthesis and biological activity of D3-trishomocubyl-4-amines.

The D3-trishomocubyl system was prepared from tertiary pentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecan-8-ols 5 in one step by using a modified Ritter reaction yielding only one of the possible two geometrical isomers of 4-amino-3-alkyl (or aryl)-D3-trishomocubane (8). Promising antagonism of reserpine-induced catalepsy was exhibited by these compounds which compared favorable with that of amantadine. Weak to mild anticholinergic properties were observed during the reduction of oxotremorine induced tremor and salivation procedure. Acute toxicities similar to that of amantadine were observed for some of these compounds. D3-Trishomocubyl-4-amines appeared as a promising new class of anti-Parkinson agents.

The adrenergic properties of ring-brominated isoprenaline analogues.

The beta 1- and beta 2-adrenoceptor activity of the 2- and 6-ring-brominated analogues of isoprenaline were evaluated in vitro. The 2-bromo-substituted analogue exhibits a far greater activity on beta 1- and beta 2-receptors than the 6-bromo-substituted analogue.

Synthesis and antimicrobial activity of a series of caespitin derivatives.

Chemical modification of the naturally occurring phlorophenone antimicrobial agent caespitin is described. These modifications include variations in the phenone side chain, substitution with prenyl, allyl, and benzyl in the 4-position of the phlorophenone nucleus, and ring cyclizations via etherification to give furan and chroman compounds. Several of these derivatives show enhanced in vitro potency over caespitin. Studies on the development of microbial resistance against these compounds show that no or very little resistance developed after several passes of these compounds in representative microbial strains.