Biomedical subjects

Per Holm

Publications and source records attributed to Per Holm.

7 recordsLinked to original sources

PubMed2005

In vivo evaluation of tablets and capsules containing spray-dried o/w-emulsions for oral delivery of poorly soluble drugs.

It is recognised that poorly soluble drugs may show an increased oral bioavailability when incorporated in o/w-emulsions. Encapsulating the emulsion lipid droplets in hydroxypropyl methylcellulose (HPMC) by spray drying has been demonstrated to preserve an improved bioavailability releasing lipid droplets from the powder in vivo. However, the spray-dried powder is cohesive and bulky requiring additional processing to improve handling. This was resolved in previous work where a directly compressible dry emulsion formulation was described. The purpose of the present study is to investigate the oral bioavailability resulting from administration of a directly compressible dry emulsion as a tablet and compare it with a HPMC dry emulsion powder and a simple lipid solution. Four female Beagle dogs received a single dose of each formulation containing the same amount of medium-chain triglycerides (MCT) and a model drug, Lu 28-179. Cyclodextrin solutions administered orally and intravenously were used as references. The absolute bioavailability decreased in the order cyclodextrin solution (0.14), HPMC dry emulsion (0.11), technically improved dry emulsion (0.10) and MCT solution (0.06). The directly compressible dry emulsion tablets were concluded to be comparable to a HPMC dry emulsion powder in terms of bioavailability. The lack of statistically significant differences relative to a MCT solution was ascribed to a low and variable absolute oral bioavailability of the model drug.

Administration, Oral↗

PubMed2004

Process characteristics and compaction of spray-dried emulsions containing a drug dissolved in lipid.

The objective of the present study is to prepare directly compressible powders, containing a poorly water-soluble drug dissolved in medium-chain triglycerides (MCT), by spray drying o/w-emulsions in a pilot plant spray dryer. In addition to the lipid phase, the emulsions contained a water-soluble carrier (a sugar), a water-insoluble carrier (magnesium alumino metasilicate) and a combined emulsifier and film-forming agent (gelatine). A factorial design was used to investigate the effect of formulation variables on the spray drying process and powder properties. The factors varied were soluble carrier type (trehalose or mannitol), insoluble carrier particle size distribution (granular or fine powder) and amount of lipid phase in the emulsion (low or high). Compressibility and compactibility of the spray-dried emulsions were mainly affected by the content of lipid in the powders and decreased on increasing the amount of lipid. Increasing the particle size of the insoluble carrier decreased spray drying process yield and lipid encapsulation efficiency whereas compactibility and handling properties were improved. Incorporation of a soluble carrier becoming amorphous on spray drying resulted in tablets with an increased mechanical strength compared to powders containing a crystalline soluble carrier.

Emulsions↗

PubMed2003

The preparation of agglomerates containing solid dispersions of diazepam by melt agglomeration in a high shear mixer.

The aim of this study was to prepare by melt agglomeration agglomerates containing solid dispersions of diazepam as poorly water-soluble model drug in order to evaluate the possibility of improving the dissolution rate. Lactose monohydrate was melt agglomerated with polyethylene glycol (PEG) 3000 or Gelucire 50/13 (mixture of glycerides and PEG esters of fatty acids) as meltable binders in a high shear mixer. The binders were added either as a mixture of melted binder and diazepam by a pump-on procedure or by a melt-in procedure of solid binder particles. Different drug concentrations, maximum manufacturing temperatures, and cooling rates were investigated. It was found to be possible to increase the dissolution rate of diazepam by melt agglomeration. A higher dissolution rate was obtained with a lower drug concentration. Admixing the binders by the melt-in procedure resulted in similar dissolution rates as the pump-on procedure. The different maximum manufacturing temperatures and cooling rates were found to have complex effects on the dissolution rate for formulations containing PEG 3000, whereas only minor effects of the cooling procedure were found with Gelucire 50/13. Gelucire 50/13 resulted in faster dissolution rates compared to PEG 3000.

Diazepam↗

PubMed2003

Validation of an image analysis method for estimating coating thickness on pellets.

A digital image analysis method for the estimation of mean pellet size and coating thickness employing optical microscopy was evaluated. The coating thickness was expressed as the difference in mean projected area radius of the uncoated and the coated pellets. The repeatability, the intermediate precision and the robustness of the image analysis method were investigated. The repeatability and the intermediate precision of the image analysis method was excellent with a low degree of scatter between the measurements. The robustness investigation on the image analysis method illustrated the importance of controlling and monitoring the illumination technique utilised. Calibration of the image analysis equipment was of the highest importance. Using pellets with a high degree of sphericity and narrow size distribution, it was sufficient to use 1000 pellets to estimate the mean pellet size and the coating thickness with an accuracy of +/-1.2 microm. An equation is presented for an approximation of the number of pellets necessary to achieve a given accuracy in the estimation of mean pellet size and coating thickness.

Drug Implants↗

PubMed2003

A new process control strategy for aqueous film coating of pellets in fluidised bed.

The parameters with effect on maximum spray rate and maximum relative outlet air humidity when coating pellets in a fluidised bed were investigated. The tested variables include type of water based modified release film coating (Eudragit NE 30D, Eudragit RS 30D, Aquacoat ECD) coating principle (top spray, bottom spray), inlet air humidity and type of pellets (sugar spheres, microcrystalline cellulose pellets). The maximum spray rate was not influenced by the coating principles. The highest spray rate was obtained for the film polymer with the lowest tackiness which is assumed to be the controlling factor. The type of pellets affected the maximum spray rate. A thermodynamic model for the coating process is employed throughout the process and not just during steady state. The thermodynamic model is incorporated into a new process control strategy. The process control strategy is based on in-process calculation of degree of utilisation of the potential evaporation energy (DUE) of the outlet air and the relative outlet air humidity (RH). The spray rate is maximised using set points of DUE and RH as control parameters. The product temperature is controlled simultaneously by regulating the inlet air temperature.

Drug Implants↗

PubMed2002

Effects of droplet size and type of binder on the agglomerate growth mechanisms by melt agglomeration in a fluidised bed.

This study was performed in order to evaluate the effects of binder droplet size and type of binder on the agglomerate growth mechanisms by melt agglomeration in a fluidised bed granulator. Lactose monohydrate was agglomerated with melted polyethylene glycol (PEG) 3000 or Gelucire 50/13 (esters of polyethylene glycol and glycerol), which was atomised at different nozzle air flow rates giving rise to median droplet sizes of 40, 60, and 80 microm. Different product temperatures were investigated, below the melting range, in the middle of the melting range, and above the melting range for each binder. The agglomerates were found to be formed by initial nucleation of lactose particles immersed in the melted binder droplets. Agglomerate growth occurred by coalescence between nuclei followed by coalescence between agglomerates. Complex effects of binder droplet size and type of binder were seen at low product temperatures. Low product temperatures resulted in smaller agglomerate sizes, because the agglomerate growth was counteracted by very high binder viscosity or solidification of the binder. At higher product temperatures, neither the binder droplet size nor the type of binder had a clear effect on the final agglomerate size.

Fats↗

PubMedDate not supplied

Tablets of functionalized polystyrene beads alone and in combination with solid reagents or catalysts. Preparation and applications in parallel solution and solid phase synthesis.

Pretreatment of polystyrene beads with a nonpolar organic solvent is the key for the generation of mechanically robust tablets consisting of neat functionalized polystyrene beads, both alone and in combination with solid reagents or catalysts. The novel dosing methodology provides accurately preweighed tablets in virtually any shape and size and with excellent disintegration properties, speeding up parallel solution and solid phase synthesis. The use of tablets is demonstrated in parallel Mitsunobu and acylation reactions.

Catalysis↗