Jan Karlsen

Alginate in Drug Delivery Systems

ABSTRACT Alginates are established among the most versatile biopolymers, used in a wide range of applications. The conventional use of alginate as an excipient in drug products generally depends on the thickening, gel-forming, and stabilizing properties. A need for prolonged and better control of drug administration has increased the demand for tailor-made polymers. Hydrocolloids like alginate can play a significant role in the design of a controlled-release product. At low pH hydration of alginic acid leads to the formation of a high-viscosity “acid gel.” Alginate is also easily gelled in the presence of a divalent cation as the calcium ion. Dried sodium alginate beads reswell, creating a diffusion barrier decreasing the migration of small molecules (e.g., drugs). The ability of alginate to form two types of gel dependent on pH, i.e., an acid gel and an ionotropic gel, gives the polymer unique properties compared to neutral macromolecules. The molecule can be tailor-made for a number of applications. So far more than 200 different alginate grades and a number of alginate salts are manufactured. The potential use of the various qualities as pharmaceutical excipients has not been evaluated fully, but alginate is likely to make an important contribution in the development of polymeric delivery systems. This natural polymer is adopted by Ph.Eur. It can be obtained in an ultrapure form suitable for implants. This review discusses the present use and future possibilities of alginate as a tool in drug formulation.

Studies on curcumin and curcuminoids

ZusammenfassungEs wurde die Kinetik des pH-abhängigen Curcumin-Abbaus untersucht. Eine Darstellung der Geschwindigkeitskonstante gegen die pH-Werte liefert die pKa-Werte des sauren Protonen. Diese Kurve zeigt aber gleichzeitig die Komplexität des Curcumin-Abbaus an.SummaryThe kinetics of the pH-dependant degradation of curcumin has been investigated. A plot of the rate constant against pH indicates the pKa values of the acid protons. The graph also indicates the complexity of the curcumin degradation.

Bioadhesion of hydrated chitosans : an in vitro and in vivo study

Abstract The (bio)adhesivity of several chitosan chloride samples was screened in vitro and compared with hydroxypropyl-methylcellulose (HPMC), Carbopol 934P and polycarbophil by a force of detachment method. This revealed differences between samples, but was judged to be insufficient to describe the bioadhesive behaviour of fully hydrated chitosan. Therefore, an ex vivo method was designed, where freshly excised cattle corneas were treated with tritiated chitosan in solution. The contact time, pH, ionic strength and chitosan molecular weight were investigated by means of factorial design, and were shown to have significant effects on the adsorption. In addition, interactions were seen between the parameters. These effects were not seen when chitosan was incubated with polycarbonate membranes instead of corneas. It is concluded that fully hydrated chitosan has a specific bioadhesive activity towards biological surfaces. In the in vivo study, liposomes and chitosan-coated liposomes containing 125I-labelled bovine serum albumin (BSA) as a marker were applied to the eyes of anaesthetised rats and their retention at 10, 30 and 90 min compared. Both formulations showed significantly longer retention than a solution of the free 125I-BSA, but coating the liposomes with chitosan did not significantly improve their retention. It is concluded that the adhesive interaction between chitosan and a biological substrate is dependent on formulation factors as well as the chitosan quality.

Studies on curcumin and curcuminoids VIII. Photochemical stability of curcumin

ZusammenfassungDie photochemische Stabilität von Curcumin wurde untersucht und die Hauptprodukte der Spaltung identifiziert. Die Abbau- und Halbzeit-Reaktionen des Curcumins in verschiedenen Lösungsmitteln und im festen Zustand werden beschrieben.SummaryThe photodecomposition of curcumin when exposed to UV/visible radiation is studied. The main degradation products are identified. The reaction mechanisms are investigated and the order of the over-all degradation reactions and the half-lives of curcumin in different solvents and in the solid state are determined.

Interactions between liposomes and chitosan

Abstract Negative and neutral liposomes were coated with the cationic polysaccharide chitosan, and the interaction was studied by photon correlation spectroscopy (PCS), electrophoretic light scattering (ELS) and cryo-electron microscopy. As shown with ELS, both types of liposomes had a reproducible change in zeta potential after coating. Electron micrographs showed no visible change in individual liposomes, but a limited degree of aggregation for neutral and a more extensive formation of liposomal clusters for negative liposomes. After centrifugation and washing, the liposomes were still coated and appeared unchanged on the electron micrographs.

Kinetics of thiamin and thiamin phosphate esters in human blood, plasma and urine after 50 mg intravenously or orally

SummaryThe concentrations of thiamin and thiamin monophosphate and diphosphate in plasma and whole blood samples were assessed in six healthy subjects for 12 h and in urine for 24 h following an IV and PO bolus dose of 50 mg thiamin HCl.Unphosphorylated thiamin increased rapidly in plasma after IV administration and then decreased to its initial value within 12 h in all but one subject; the half-life was 96 min. Thiamin mono and -diphosphate increased moderately (56%), and decreased slowly; the half-life of diphosphate was 664 min. Within 24 h, 53% of the administered dose was recovered in the urine, indicating a restricted distribution.After oral administration, the peak thiamin concentration in plasma was reached after 53 min and the concentration then had increased to 179% of its initial value. The elimination half-life was 154 min, and only 2.5% of the given dose was recovered in the urine. The relative bioavailability of thiamin was 5.3%. A moderate amount of the administered thiamin was stored in blood.Other body tissues must play an important part, therefore, in the distribution of thiamin.

Concomitant determination of thiamin and its phosphate esters in human blood and serum by high-performance liquid chromatography

A high-performance liquid chromatographic method for the simultaneous determination of thiamin and thiamin phosphate esters in human blood or serum has been developed. The eluent consists of acetonitrile and phosphate buffer, in the ratios 90:10 (v/v) for the elution of thiamine and 60:40 (v/v) for the phosphate esters. The four compounds are eluted within 15 min. The detection limit is 13-16 fmol. Between-assay variation is 5-11%. Samples of whole blood and serum from 30 healthy adults were analysed. The following reference values were obtained for 15 females 15 males (nM, mean +/- S.D.). In serum: thiamin, 10.9 +/- 2.9/16.9 +/- 3.3; thiamin monophosphate, 8.3 +/- 1.5/3.7 +/- 1.5. In whole blood: thiamin, 29.6 +/- 10.0/33.4 +/- 10.4; thiamin monophosphate, 9.7 +/- 2.3/10.9 +/- 5.1; thiamin diphosphate, 121 +/- 29.6/165 +/- 40.4.

Micelle-like structures in human saliva

Abstract The acquired enamel pellicle can easily be visualized by scanning electron microscopy (SEM) at low magnifications, and some researchers have described the surface morphology of the acquired pellicle as being predominantly globular based on scanning and transmission electron microscopic examinations. This is consistent with the adsorption of salivary protein aggregates in the form of globular or micelle-like structures comprising amphiphilic salivary proteins. The aim of the present study was to demonstrate the presence of and to characterize possible globular structures of human saliva. Parotid saliva was collected from three healthy individuals and examined by transmission electron microscopy, photon correlation spectroscopy (PCS) and zeta potential determinations. TEM examinations (negative staining with a 2% ammonium molybdate solution) demonstrated globular structures in parotid saliva in the size range 150–200 nm. The globular structures appeared to be more clustered (comprising 6–10 globules) with increasing time after sampling. The PCS analyses likewise demonstrated particles in parotid saliva with an initial size in the range 100–150 nm. Unimodal analysis showed that the mean hydrodynamic diameter of the salivary particles increased to about 450 nm 50 min after sampling. Size distribution processor (SDP) analyses, furthermore, indicated the presence of three different size fractions of the salivary particles; one in the size range of about 10 nm, one in the size range of 40–110 nm and one of 240–500 nm. Initial addition of 0.5 ml of 50 mM pyrophosphate solution (PP) to the saliva samples seemed to inhibit the increase in size of the globular structures, which were then less than 50 nm. Addition of PP to the saliva samples 120 min after sampling, disintegrated the globular structures, as the unimodal mean of the particle size decreased from about 450 nm to 100–150 nm. The PCS intensity (counts s −1 ) also decreased. Zeta potential determinations indicated an overall net negative surface charge of the salivary globular structures of about −13 to −17 mV. The study clearly demonstrated the presence of negatively charged globular structures of human parotid saliva in the size range of about 100–500 nm, consistent with micelle-like structures consisting of amphiphilic salivary proteins. Calcium seems furthermore to be of importance in maintaining the structure of these salivary particles.

Interactions between liposomes and chitosan II : effect of selected parameters on aggregation and leakage

The interaction between liposomes and chitosan has been described in an earlier paper. In the present work, the production of liposome-chitosan complexes (Chitosomes) was further studied using factorial designs. The parameters studied were the stirring rate, rate of addition of liposomes to polymer, ionic strength, chitosan quality, lipid/polymer ratio and pH. Particle size, polydispersity and charge were the measured parameters. Cryo-electron microscopy was used for further study of one of the combinations. It was found that the ionic strength, chitosan quality, lipid/polymer ratio and pH had a significant effect on the resulting aggregate size. The leakage of quinine from Chitosomes was compared to the leakage from liposomes using a fractional dialysis method. The leakage rates were similar, but the Chitosomes produced a higher initial release and showed less scattering of the data. Measurements of zeta potential indicated adsorption of quinine to the liposomal membrane. Chitosomes could be stored in a refrigerator for at least 6 months without significant change in particle size.

Electrical methods for skin moisture assessment

Skin sites on 8 test subjects were treated with moisturizers, and different electrical measuring methods were compared regarding their quality in the assessment of the induced changes in the stratum corneum hydration level. Low frequency susceptance measurements were found preferable to high frequency admittance measurements, and the advantages of monopolar measurements with the three-electrode system are described.