Sven Gohla - Academia.edu (original) (raw)
Papers by Sven Gohla
European Journal of Pharmaceutical Sciences, 1996
Drug nanocrystals are a formulation principle for systemic and also intracellular delivery of poo... more Drug nanocrystals are a formulation principle for systemic and also intracellular delivery of poorly soluble drugs. Their production by bottom up techiques (precipitation – hydrosols, Nanomorph) and by top down techniques (bead milling – NanoCrystal®, high pressure homogenization – DissoCubes®, NANOEDGE®) is briefly described, representing the first generation of nanocrystals. The second generation, the smartCrystal®, is produced by combination processes. They are featured by e.g. increased physical stability and/or smaller sizes (<100 nm), favourable when exposed to the destabilizing electrolytes in biological fluids and for uptake by cells by pinocytosis. The lab scale processes were successfully transferred to industrial scale by using discontinuous bead mills and high capacity homogenizers (top down), precipitation can be performed by static blenders. According to the nanotoxicological classification system (NCS), the nanocrystals belong to class I, being highly tolerable. They can be produced using only regulatorily accepted excipients. Both ease the way to the patient and market. Nanotoxicity studies confirm the good tolerability. The nanocrystal products on the market are no direct intracellular delivery systems. They transport drug to the biological barrier and then promote penetration and permeation of drugs in molecular form through barriers and cellular membranes (cellular delivery mechanism I). Formulations based on the cellular uptake of nanocrystals are still in development (cellular delivery mechanism II). Examples are i.v. targeting to endothelial cells of the blood-brain barrier and the loading of blood cells (monocytes, erythrocytes) to use these cells as transport vehicles for the nanocrystals. By now, very little work has been done to study and actively modulate the intracellular fate of nanocrystals.
European Journal of Pharmaceutics and Biopharmaceutics, 2011
Journal of Microencapsulation, 2002
Solid lipid nanoparticles (SLN) were produced by high pressure homogenization using piston-gap ho... more Solid lipid nanoparticles (SLN) were produced by high pressure homogenization using piston-gap homogenizers. Batch sizes varied between 40 ml and 50 l. Because of the different batch sizes, different homogenizer types were used, but the same functional principles were maintained, and the change from 40 ml to 50 l was not critical. With increasing batch sizes, the product quality in terms of particle size distribution and physical storage stability improved. Medium scale (30 l and 50 l) drug-free and drug-loaded SLN batches could be produced reproducibly and batch-to-batch uniformity was proven: within one batch particle sizes were homogeneous. This study revealed the influence of pressure and temperature for the hot homogenization technique A change of pressure between 300-500 bars induced only minor differences in particle size, but some influence of the heating temperature was found. More important than control of the heating process was the control of the cooling process of the final product. A too rapid cooling deteriorated the product quality: cooling with water of 18 degrees C proved to be the optimum cooling condition.
European Journal of Pharmaceutics and Biopharmaceutics, 2000
To evaluate the potential use of solid lipid nanoparticles (SLN) in dermatology and cosmetics, gl... more To evaluate the potential use of solid lipid nanoparticles (SLN) in dermatology and cosmetics, glyceryl behenate SLN loaded with vitamin A (retinol and retinyl palmitate) and incorporated in a hydrogel and o/w-cream were tested with respect to their influence on drug penetration into porcine skin. Conventional formulations served for comparison. Excised full thickness skin was mounted in Franz diffusion cells and the formulations were applied for 6 and 24 h, respectively. Vitamin A concentrations in the skin tissue suggested a certain drug localizing effect. High retinol concentrations were found in the upper skin layers following SLN preparations, whereas the deeper regions showed only very low vitamin A levels. Because of a polymorphic transition of the lipid carrier with subsequent drug expulsion following the application to the skin, the drug localizing action appears to be limited for 6-24 h. Best results were obtained with retinol SLN incorporated in the oil-in-water (o/w) cream retarding drug expulsion. The penetration of the occlusion sensitive drug retinyl palmitate was even more influenced by SLN incorporation. Transepidermal water loss (TEWL) and the influence of drug free SLN on retinyl palmitate uptake exclude pronounced occlusive effects. Therefore enhanced retinyl palmitate uptake should derive from specific SLN effects and is not due to non-specific occlusive properties.
Journal of Microencapsulation, 2005
This study describes the development, preparation and characterization of solid lipid nanoparticl... more This study describes the development, preparation and characterization of solid lipid nanoparticles (SLN) containing the novel anti-ageing substance alpha-lipoic acid. Lipoic acid is chemically labile, i.e. the degradation products possess an unpleasant odour. Therefore, the active was encapsulated in SLN. A lipid with low melting point (Softisan 601) was selected for preparation of active-loaded SLN after screening the solubility of alpha-lipoic acid in physicochemically different lipids. An entrapment efficiency of 90% (UV analysis) was obtained for all developed formulations using Miranol Ultra C32 as emulsifying agent. Particle size stability was monitored during 3 months storing the samples at 20 degrees C and at 4 degrees C. Results of DSC analysis confirm that these systems are characterized by a solid-like behaviour, although with a very low crystallinity index.
Journal of Microencapsulation, 2002
... Solid lipid nano-particles can combine physical integrity of particle shape (Dingler 1998) as... more ... Solid lipid nano-particles can combine physical integrity of particle shape (Dingler 1998) as well as j. microencapsulation, 2002, vol. 19, no. 1, 11±16 * To whom correspondence should be addressed; e-mail: gohla.sven@juvena.ch ...
Journal of Controlled Release, 2000
European Journal of Pharmaceutics and Biopharmaceutics, 2000
Journal of Dermatological Science, 1998
Bulletin of Experimental Biology and Medicine, 1991
European Journal of Pharmaceutical Sciences, 1996
Drug nanocrystals are a formulation principle for systemic and also intracellular delivery of poo... more Drug nanocrystals are a formulation principle for systemic and also intracellular delivery of poorly soluble drugs. Their production by bottom up techiques (precipitation – hydrosols, Nanomorph) and by top down techniques (bead milling – NanoCrystal®, high pressure homogenization – DissoCubes®, NANOEDGE®) is briefly described, representing the first generation of nanocrystals. The second generation, the smartCrystal®, is produced by combination processes. They are featured by e.g. increased physical stability and/or smaller sizes (<100 nm), favourable when exposed to the destabilizing electrolytes in biological fluids and for uptake by cells by pinocytosis. The lab scale processes were successfully transferred to industrial scale by using discontinuous bead mills and high capacity homogenizers (top down), precipitation can be performed by static blenders. According to the nanotoxicological classification system (NCS), the nanocrystals belong to class I, being highly tolerable. They can be produced using only regulatorily accepted excipients. Both ease the way to the patient and market. Nanotoxicity studies confirm the good tolerability. The nanocrystal products on the market are no direct intracellular delivery systems. They transport drug to the biological barrier and then promote penetration and permeation of drugs in molecular form through barriers and cellular membranes (cellular delivery mechanism I). Formulations based on the cellular uptake of nanocrystals are still in development (cellular delivery mechanism II). Examples are i.v. targeting to endothelial cells of the blood-brain barrier and the loading of blood cells (monocytes, erythrocytes) to use these cells as transport vehicles for the nanocrystals. By now, very little work has been done to study and actively modulate the intracellular fate of nanocrystals.
European Journal of Pharmaceutics and Biopharmaceutics, 2011
Journal of Microencapsulation, 2002
Solid lipid nanoparticles (SLN) were produced by high pressure homogenization using piston-gap ho... more Solid lipid nanoparticles (SLN) were produced by high pressure homogenization using piston-gap homogenizers. Batch sizes varied between 40 ml and 50 l. Because of the different batch sizes, different homogenizer types were used, but the same functional principles were maintained, and the change from 40 ml to 50 l was not critical. With increasing batch sizes, the product quality in terms of particle size distribution and physical storage stability improved. Medium scale (30 l and 50 l) drug-free and drug-loaded SLN batches could be produced reproducibly and batch-to-batch uniformity was proven: within one batch particle sizes were homogeneous. This study revealed the influence of pressure and temperature for the hot homogenization technique A change of pressure between 300-500 bars induced only minor differences in particle size, but some influence of the heating temperature was found. More important than control of the heating process was the control of the cooling process of the final product. A too rapid cooling deteriorated the product quality: cooling with water of 18 degrees C proved to be the optimum cooling condition.
European Journal of Pharmaceutics and Biopharmaceutics, 2000
To evaluate the potential use of solid lipid nanoparticles (SLN) in dermatology and cosmetics, gl... more To evaluate the potential use of solid lipid nanoparticles (SLN) in dermatology and cosmetics, glyceryl behenate SLN loaded with vitamin A (retinol and retinyl palmitate) and incorporated in a hydrogel and o/w-cream were tested with respect to their influence on drug penetration into porcine skin. Conventional formulations served for comparison. Excised full thickness skin was mounted in Franz diffusion cells and the formulations were applied for 6 and 24 h, respectively. Vitamin A concentrations in the skin tissue suggested a certain drug localizing effect. High retinol concentrations were found in the upper skin layers following SLN preparations, whereas the deeper regions showed only very low vitamin A levels. Because of a polymorphic transition of the lipid carrier with subsequent drug expulsion following the application to the skin, the drug localizing action appears to be limited for 6-24 h. Best results were obtained with retinol SLN incorporated in the oil-in-water (o/w) cream retarding drug expulsion. The penetration of the occlusion sensitive drug retinyl palmitate was even more influenced by SLN incorporation. Transepidermal water loss (TEWL) and the influence of drug free SLN on retinyl palmitate uptake exclude pronounced occlusive effects. Therefore enhanced retinyl palmitate uptake should derive from specific SLN effects and is not due to non-specific occlusive properties.
Journal of Microencapsulation, 2005
This study describes the development, preparation and characterization of solid lipid nanoparticl... more This study describes the development, preparation and characterization of solid lipid nanoparticles (SLN) containing the novel anti-ageing substance alpha-lipoic acid. Lipoic acid is chemically labile, i.e. the degradation products possess an unpleasant odour. Therefore, the active was encapsulated in SLN. A lipid with low melting point (Softisan 601) was selected for preparation of active-loaded SLN after screening the solubility of alpha-lipoic acid in physicochemically different lipids. An entrapment efficiency of 90% (UV analysis) was obtained for all developed formulations using Miranol Ultra C32 as emulsifying agent. Particle size stability was monitored during 3 months storing the samples at 20 degrees C and at 4 degrees C. Results of DSC analysis confirm that these systems are characterized by a solid-like behaviour, although with a very low crystallinity index.
Journal of Microencapsulation, 2002
... Solid lipid nano-particles can combine physical integrity of particle shape (Dingler 1998) as... more ... Solid lipid nano-particles can combine physical integrity of particle shape (Dingler 1998) as well as j. microencapsulation, 2002, vol. 19, no. 1, 11±16 * To whom correspondence should be addressed; e-mail: gohla.sven@juvena.ch ...
Journal of Controlled Release, 2000
European Journal of Pharmaceutics and Biopharmaceutics, 2000
Journal of Dermatological Science, 1998
Bulletin of Experimental Biology and Medicine, 1991