Enhanced dissolution and bioavailability of gliclazide using solid dispersion techniques

Gliclazide is practically insoluble in water and its bioavailability is limited by dissolution rate. To enhance the dissolution rate and bioavailability the present study was aimed to formulate solid dispersions using different water soluble polymers such as polyethylene glycol 4000 (PEG 4000), polyethylene glycol 6000 (PEG 6000) using fusion method and polyvinyl pyrrolidone K- 30 (PVP K 30) by solvent evaporation method. The interaction of gliclazide with the hydrophilic polymers was studied by Differential Scanning Calorimetry (DSC), Fourier Transformation-Infrared Spectroscopy (FTIR) and X-Ray diffraction analysis. Solid dispersions were characterized for physicochemical properties like drug content, surface morphology and dissolution studies. Various factors like type of polymer and ratio of the drug to polymer on the solubility and dissolution rate of the drug were also evaluated. Pharmacokinetic studies of optimized formulation were compared with pure drug and marketed formulation in wistar rats. The dissolution of the pure drug and solid dispersion prepared with PVP K 30 (1:1) showed 38.3 + 4.5 % and 95 + 5.2 % release respectively within 30 min. Peak plasma concentration of pure drug, solid dispersion (PVP K 30) and marketed formulation was found to be 8.76 + 2.5, 16.04 + 5.5 and 9.24 + 3.6 g/ml respectively, from these results it was observed that there is two fold increase in peak plasma concentration compared to pure drug. Solid dispersion is an effective technique in increasing solubility, dissolution rate and bioavailability of the poorly soluble drugs.

Factors affecting the pharmacokinetics of herbal preparations and their impact on the outcome of clinical trials

This paper summarizes research on the pharmacokinetic characteristics of popular herbal medicines (such as Hypericum perforatum, Echinacea, Camellia sinensis, Tanacetum parthenium and Ginkgo biloba) in human studies, and in in vitro and in vivo systems. The effects of extract formulation, dosing frequency and biotransformation on the absorption and bioavailability of herbal drugs are briefly discussed.

Oral agents in the treatment of type 2 diabetes

The tools available to the physician involved in the management of type 2 diabetes expanded dramatically in the 1990s and the prospects for continued expansion of the theraputic repertoire are good. The newer agents target different features of the syndrome of type 2 diabetes, and offer the prospect of being able to tailor drug therapy according to the needs of individual patients who might differ in the balance of aetiological risk factors for type 2 diabetes. The cost of the newer agents and the lack of comparative clinical studies with hard end-points currently limit their use, and a new generation of comparative clinical studies is required before we can face up to this challenge. The fact that Asia and Africa are the regions with the greatest potential increase in the prevalence of type 2 diabetes makes further cost reductions in the provision of these drugs a priority (AU)

Erythromycin and the newer macrolides

Recent macrolide development has been directed by clinical pharmacology dictates, ethical considerations, and patient concerns. Patient non-compliance, a major repercussion from erythromycin's side-effects, produces lost clientele, resistent bacterial strains, and escalating costs for the patient and healthcare system. Structural alteration of the macrolide molecule (after its macrocyclic lactone ring), has enhanced the antibacterial spectrum, pharmacokinetics, tissue penetration, and drug tolerance. New macrolide derivatives differ from the proto-type (erthromycin) in pharmacokinetic and dynamic profiles, and include roxithromycin, dirithromycin, clarithromycin, and azithromycin. Josamycin is less active than erythromycin. This review discusses the new macrolides widely used in the Caribbean, with reference to erythromycin (AU)

Prediction of serum-theophylline level using the disease factor product a pilot study - abstract

In this pilot study, we examined the performance of a population-based pharmacokinetic model designed to predict serum theophylline levels in patients with compromised pulmonary function. Ten patients were followed prospectively and the measured steady-state theophylline levels were compared with the predicted levels, that were calculated with formulae based on the disease factor product (DFP). DFP is the combined product of all factors that are known to influence theophylline clearance. In this way, an individualized theophylline clearance could be calculated and a prediction for the steady-state serum level of theophylline could be made. We found no significant difference between the predicted and measured theophylline levels, regardless of whether DFP was calculated with all present factor (approach 1) or with only the largest enhancing and the largest inhibiting factors (approach 2) present. For individual patients the best correlation (R = 0.68) between measured and predicted levels was found with approach 1. Therefore, there is evidence from this pilot study, that the pharmacokinetic model performs in a clinically acceptable manner and could be used to individualize theophyline therapy and adjust the dosage regimen to changes in patients' disease factors(AU)

Multiple intraosseous sites versus peripheral intravenous sites in a pig model comparison of drug pharmacokinetics - abstract

The pharmacokinetics of injected sodium bicarbonate and radioactive tracers were studied from various intraosseous (IO) sites and a peripheral intravenous (IV) site. Anaesthetised piglets (12-23kg) were catheterised with peripheral 22-gauge IV catheters and 18-gauge bone marrow needles in the medial malleolar, tibial, femoral and humeral IO sites. Standardised aliquots of NaHCO3, (1meq/kg) and Tc-99m DTPA (600 micro-curies) were injected at randomly selected sites. The initial time and maximal level of CO2 rise after NaHCO3 injected were monitored using an end tidal CO2 monitor. The initial time to reach, and proportion of injected tracer in the central circulation were determined using radioactivity counter measure of carotid blood samples drawn at 1.5 second intervals for 1 minute and at 2, 5, 10, 20, 30, and 40, minutes. The following kinetics were determined: SAS analysis by ANOVA. KINETICS - DTPA time to carotid (sec); Tracer amount/Total dose (percentage total dose; Initial CO2 rise (sec);Maximal CO2 rise (mmHg);- IV - 12.8, .032, 12.8 9.6 respectively; HUMERUS - 12.0, .048, 12.0, 8.4 respectively; FEMUR - 13.5, .035, 12.6, 8.1 respectively; ANKLE - 18.6, .037, 13.6, 7.3 respectively; TIBIA - 17.3, .033, 12.9, 12.9 respectively. There was no statistically significant difference (p>.05) in the following: 1) Time of initial expired CO2 rise, 2) Maximal expired CO2 rise, 3) Time of tracer to reach the central circulation from IO and IV sites. Our study suggests: (1) IO and IV sites are similarly rapid means of injection delivery to the central circulation, (2) adjustments in dosages of medication may not be required to achieve the same IO effects as IV injection (AU)