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Biomedical subjects

H G Kristensen

Publications and source records attributed to H G Kristensen.

17 recordsLinked to original sources
PubMed2001

Technical optimisation of redispersible dry emulsions.

Preparation of dry emulsions suitable for tablet processing was examined in this study. Liquid o/w-emulsions were spray dried in a laboratory spray dryer applying hydroxypropylmethylcellulose (HPMC) as a solid carrier and emulsifier. As the lipid phase, fractionated coconut oil was used. The ability of various excipients to increase the density of dry emulsions was investigated. Adding sucrose to the formulation, redispersible dry emulsions with higher density were obtained. The type of rotary atomizer did not affect the dry emulsions containing sucrose nor the rate of rotation of the atomizer applied in the spray drying process. By wet granulation, using ethanol as a binder, free-flowing and compactable dry emulsions were obtained and simultaneously the reconstitution properties were preserved. It was concluded that dry emulsions could be optimised for tablet processing by wet granulation. Tablets having a lipid content up to 20% had proper tablet properties.

Emulsions↗
PubMed2001

Preparation of redispersible dry emulsions by spray drying.

Development of stable dry emulsions being able to reform the original o/w-emulsion by reconstitution in water is presented. Dry emulsions were prepared by spray drying liquid o/w-emulsions in a laboratory spray dryer. Three hydroxypropylmethylcellulose (HPMC) types were applied as solid carrier and emulsifier. The lipid phase was fractionated coconut oil. The ratio of solid carrier to lipid phase influenced the reconstitution properties. It was possible to prepare redispersible dry emulsions of a lipid content up to 40% dry powder mass. The different HPMC types had no noticeable effect on the reconstitution properties, but too viscous liquid o/w-emulsions were difficult to atomise. The type of rotary atomizer, or the rate of rotation did not affect the technical properties of the dry emulsions containing 40% lipid. It was concluded that low viscosity HPMC was a useful solid carrier. The dry emulsions remained physically stable for at least 6 months.

Drug Compounding↗
PubMed2001

Direct estimation of the in vivo dissolution of spironolactone, in two particle size ranges, using the single-pass perfusion technique (Loc-I-Gut) in humans.

AIM: The objective of this in vivo dissolution study was to investigate the usefulness of the Loc-I-Gut technique for differentiating between the in vivo dissolution rate of two particle sizes of spironolactone, and to compare these in vivo results with corresponding in vitro data. METHODS: The study included six volunteers, and consisted of three sequential parts (I, II, III). In parts I and III the in vivo dissolution was measured directly by perfusing a semi-open segment in the proximal jejunum. In part II, a solution of spironolactone was administered orally, and the plasma concentration time profile was followed for 48 h. The in vitro dissolution was measured using flow-through cells and different dissolution media simulating human gastrointestinal fluids. RESULTS: A difference in in vivo dissolution rate of the two different particle sizes was observed, based on perfusion data. This difference was not pronounced in the relative bioavailability of spironolactone administered in two different particle sizes. The relative bioavailability was dependent on the bile acid concentration in vivo. In vitro, dissolution rate of the smaller particles was improved at fasted state bile acid concentrations, while the larger particles were only significantly affected at fed state bile acid concentrations. CONCLUSION: In vivo dissolution studies discriminated between the dissolution rate of the two different particle sizes of spironolactone, based on the perfusate samples. The lack of difference in relative bioavailability, might be explained by the insufficient wash-out of particles after ending the perfusion, reabsorption of surface active ingredients along the GI tract, relatively small difference in particle size and the large inter- and intra-individual differences in pharmacokinetic variables.

Adsorption↗
PubMed2000

Dissolution of hydrocortisone in human and simulated intestinal fluids.

PURPOSE: To compare solubility and dissolution rate of hydrocortisone in aspirated human intestinal fluids (HIFs) with simulated intestinal fluids (SIFs) and buffer. METHODS: Solubility and flux from a rotating disk of hydrocortisone were measured. The bile salt content, pH and osmotic pressure were determined in HIFs. RESULTS: In fasted state the solubility of hydrocortisone was higher in HIFs than in the buffer and SIFs. The flux of hydrocortisone in HIFs was similar to the flux in the buffer but lower than the flux in SIFs at fasted state. Addition of intestinal surfactants in SIFs increased solubility and flux at both fasted and fed state. The increase in solubility was caused by micelle formation in SIFs. The increase in flux may partly be explained by increased solubility. The bile salt content of the HIFs did not correlate with the solubility or the flux but pH in the HIFs seems to have some effect on the components of the HIFs resulting in increased solubility. CONCLUSIONS: It is possible to perform comparable dissolution tests in HIFs and SIFs. The lack of correlation between the results in HIFs and the bile salt content may be explained by the relatively low lipophilicity of the model drug.

Anti-Inflammatory Agents↗
PubMed1999

Growth mechanisms in melt agglomeration with a low viscosity binder.

Lactose monohydrate was melt agglomerated in an 8-l high shear mixer using stearic acid as meltable binder. The impeller speed was varied at six levels, and the temperature of the heating jacket was varied at three levels. The agglomerate growth mechanisms were found to be different from those observed in previous melt agglomeration experiments. This is attributed to the low viscosity of the molten stearic acid. A higher impeller speed and a higher jacket temperature resulted in an agglomerate growth that was markedly affected by comminution and accordingly gave rise to agglomerates of a wider size distribution and a higher porosity. A lower impeller speed and a lower jacket temperature resulted in smoother and more spherical agglomerates.

Chemistry, Pharmaceutical↗
PubMed1999

Electrostatic charging during a melt agglomeration process.

Lactose monohydrate was melt agglomerated in an 8-l high shear mixer using stearic acid, polyethylene glycol (PEG) 3000, and a mixture of stearic acid and glycerol monostearate as meltable binders. Electrostatic charging during processing at relative air humidities of 35 and 75%, respectively, was estimated from the voltage of a monitoring probe inserted into the mixer. Stearic acid produced a high level of electrostatic charges, whereas PEG 3000 gave rise to a markedly lower level. Addition of glycerol monostearate to the stearic acid reduced the level of electrostatic charges. A correlation was found between the resistivity of the binder and the level of electrostatic charges in the material. With the stearic acid and the binder mixture, the level of electrostatic charges was higher at a low air humidity. The amount of adhesion to the bowl was found to depend on the level of electrostatic charges.

Chemical Phenomena↗
PubMed1999

Evaluation of melt agglomeration properties of polyethylene glycols using a mixer torque rheometer.

Lactose was melt agglomerated in a mixer torque rheometer with polyethylene glycol (PEG) 2000, 3000, 6000, 8000, 10 000, or 20 000 as meltable binder. A longer massing time caused an increase in mean torque until a maximum value after which the torque decreased. A smaller particle size of the PEG gave rise to a faster initial rise in mean torque. The higher viscosity of the PEG 20 000 resulted in a higher mean torque, whereas no clear difference in mean torque was obtained with the other PEGs. The binder concentration could be varied within a rather wide range without causing overwetting, the range being wider with PEG 3000 than with PEG 20 000. The mean torque values obtained were found to be related to the liquid saturation of the agglomerates. The reproducibility of the experiments was found to be very dependent on the experimental conditions, the highest binder viscosities and binder concentrations giving rise to a poor reproducibility. The results were compared with a few melt agglomeration experiments with PEG 3000 in a high shear mixer. The mixer torque rheometer was found not to be suitable for predicting melt agglomeration properties in the high shear mixer because of a marked difference in the shear forces in the two mixers.

Agglutination↗
PubMed1999

A comparison between direct determination of in vivo dissolution and the deconvolution technique in humans.

AIM: The primary objective of this study was to investigate the in vivo dissolution of carbamazepine in humans and to compare it with the dissolution estimated by deconvolution of plasma concentrations as well as the in vitro dissolution. METHODS: The in vivo study included six healthy volunteers, and consisted of two sequential parts. In part 1 the dissolution was measured by perfusing a semi-open segment in the proximal jejunum in humans. In part 2 the volunteers were given a solution of carbamazepine orally. In both parts of the study, plasma samples were collected up to 48 h after administration of the dose. The in vitro dissolution was measured in a flow-through cell using dissolution medium with and without the addition of bile acids (3 mM). RESULTS: The direct measured in vivo dissolution profile of carbamazepine and the deconvoluted profile were found to be similar. The two dissolution profiles of carbamazepine obtained in vitro were statistically lower than the two in vivo dissolution profiles. The higher in vivo dissolution rate is probably due to efficient sink conditions as a consequence of the high permeability of carbamazepine and more pronounced intestinal motility. CONCLUSION: The jejunal perfusion system was successfully used for in vivo dissolution measurements of carbamazepine and agreed with the deconvoluted plasma profile regarding rate and extent of dissolution. Single-pass perfusion is therefore a meaningful tool for further studies of in vivo dissolution.

Algorithms↗
PubMed1999

Quantitative analysis of povidone (PVP) in drug-PVP matrix using multicomponent analysis.

A method for the quantification of povidone (PVP), in solid dispersions and physical mixtures of the polymer and a very slightly soluble drug substance, has been developed by multicomponent analysis using the concepts of chemometrics. Because the UV-absorbance spectra of PVP is completely overlapped by the UV-absorbance spectra of the drug substance, a direct spectrophotometric method of PVP is impossible. However, UV-spectrophotometric data were analyzed by the Quant + Perkin Elmer software for quantitative multicomponent analysis using chemometrics, and by the optimal method developed using a solvent of pH 7.4, a fast, reliable, and precise detection of PVP was obtained when the content of PVP in the powder sample exceeded 20% (m/m). Two methods were developed by the calibration procedure, using buffers of pH 7.4, respectively pH 8.5. By applying a solvent of pH 8.5, more sample could be taken into use because of the enhanced solubility of the drug substance, and hence it was believed that as more PVP was taken into use, a better prediction of PVP would be obtained. However, as more drug substance was taken into use the UV-absorbance spectrum of PVP was even more overlapped, and an inferior prediction was obtained.

Calibration↗