| 1. |
- Adane, M., et al.
(författare)
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The use of extragranular disintegrants in multiple-unit tablet formulations : effect on compressibility, compactibility and disintegration
- 2007
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Ingår i: Journal of drug delivery science and technology. - 1773-2247. ; 17:4, s. 279-284
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Tidskriftsartikel (refereegranskat)abstract
- Multiple-unit tablets formed from mixtures of microcrystalline cellulose pellets and disintegrants (Ac-Di-Sol, Primojel or Kollidon CL) by compaction were investigated with the aim of controlling tablet tensile strength and disintegration time. The effects of pellet porosity, compaction pressure, and type and amount of disintegrant were studied. Primojel made the pellets less prone to deformation during compression, while the other two disintegrants had very minor effects on the compression behavior. Ac-Di-Sol and Primojel generally increased the tablet tensile strength, whereas the effect of Kollidon CL was dependent on the initial pellet porosity. Kollidon CL was found to significantly reduce the disintegration time, but the other two disintegrants had variable efficacy, and for the low-porosity pellets significantly increased the disintegration time. These results are interpreted as resulting from the interplay between the mechanical characteristics of the pellets and the mechanisms of action of the disintegrants.
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| 2. |
- Bramer, Tobias, et al.
(författare)
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Effects of pH and ionic strength on catanionic drug-surfactant mixtures used for prolonged release from gels.
- 2007
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Ingår i: Journal of drug delivery science and technology. - 1773-2247. ; 17:4, s. 285-291
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the influence of pH and ionic strength on the phase behavior of two different catanionic drug-surfactant mixtures, and to study drug release from gels facilitated by the catanionic aggregates. Simplified phase diagrams were constructed for diphenhydramine or tetracaine mixed with SDS, varying the pH approximately between 6 and 11, and the NaCI concentration from 0.45 to 1.8%. The phases formed were studied visually, rheologically and with cryo-TEM. Some mixtures containing catanionic vesicles and micelles were selected for drug release studies from gels, varying the pH and NaCI concentration here as well. Both catanionic systems investigated proved relatively resilient to changes in the ionic strength. Changes in pH, on the other hand, caused marked effects to the phase behavior in both systems. The influence of pH was particularly strong in the drug-rich part of the tetracaine/SDS system, where increasing the pH causes precipitation. As expected, the drug release in both systems was somewhat affected by changes in both pH and ionic strength, but remained in all cases significantly prolonged as compared to the release of free, non-complexed, drug. These studies show that catanionic mixtures may be used to obtain prolonged drug release from gels, and that the concept also works when the gels are exposed to a pH that is a couple of units above the pKa of the cationic component. Furthermore, the ionic strength has no pronounced effect on the drug release, as long as it is kept within reasonable pharmaceutical levels.
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| 3. |
- Fichtner, Frauke, et al.
(författare)
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Drug release from compacted single inert matrix agglomerates
- 2007
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Ingår i: Journal of Drug Delivery Science and Technology. - 1773-2247. ; 17:4, s. 273-277
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Tidskriftsartikel (refereegranskat)abstract
- The effect of compaction on the drug release from single, sodium chloride loaded, microcrystalline cellulose agglomerates of different porosities was investigated in this study. The drug release from uncompacted agglomerates and from agglomerates regained from tablets compacted at a range of different compaction pressures was monitored measuring the conductivity of the dissolution medium in a recirculation flow-through system. The drug release profiles were described using the mean dissolution time (MDT), the variation of dissolution time (VDT) and the relative dispersion coefficient (RD). It was found that depending on physical structure changes of the matrix, the drug release rate of compacted agglomerates could be enhanced or retarded in comparison with uncompacted agglomerates. The retardation is suggested to be due to a densification of the matrix and the enhancement due to a crack formation in the external surface of the matrix.
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| 4. |
- Fransén, Nelly, et al.
(författare)
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The in vitro transport of dihydroergotamine across porcine nasal respiratory and olfactory mucosa and the effect of a novel powder formulation
- 2007
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Ingår i: Journal of Drug Delivery Science and Technology. - 1773-2247. ; 17:4, s. 267-271
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to investigate the transport of dihydroergotamine (DHE) across porcine nasal respiratory and olfactory mucosa and to evaluate the absorption enhancing effect of a novel dry powder formulation compared with a reference solution with the horizontal Ussing chamber method. The powder formulation was obtained by mixing micronized DHE particles and mucoadhesive carrier particles (sodium starch glycolate) to create an interactive mixture. The horizontal Ussing chamber method was chosen as the in vitro model since it provides the opportunity to apply a dry powder formulation and compare the transport across the two types of nasal mucosa. A histological evaluation confirmed that the mucosa had been correctly isolated. The results showed no significant difference in the absorption from the powder formulation compared with the reference solution, but the transport of DHE was significantly higher across olfactory mucosa than across respiratory mucosa. This may be explained by facilitated transport through paracellular transfer along the olfactory nerve cells.
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| 5. |
- Lennernäs, Hans, et al.
(författare)
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Oral drug absorption and the biopharmaceutics classification system
- 2007
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Ingår i: Journal of drug delivery science and technology. - 1773-2247. ; 17:4, s. 237-244
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Forskningsöversikt (refereegranskat)abstract
- Bioavailability (BA) and bioequivalence (BE) play a central role in pharmaceutical product development and BE studies are presently being conducted for New Drug Application (NDAs) of new compounds, in supplementary NDAsfor new medical indications and product line extensions, in Abbreviated New Drug Applications (ANDAs) of generic products and in applications for scale-up and post-approval changes. The Biopharmaceutics Classification System (BCS) has been developed to provide a scientific approach for classifying drug compounds based on solubility as related to dose and intestinal permeability in combination with the dissolution properties of the oral immediate release (IR) dosage form. The aim of BCS is to provide a regulatory tool for replacing certain BE studies by accurate in vitro dissolution tests. The aim of the present review is to present the status of BCS and discuss its future application in pharmaceutical product development. This will be discussed in relation to novel findings in human intestinal absorption, permeability and solubility. The future application of BCS is likely to be increasingly important if the BCS borders for certain Class II and III drugs are extended. The BCS is also a simple tool in early drug development to determine the rate-limiting step in the oral absorption process, which has facilitated the information between different experts involved in the overall drug development process. In the future, this increased awareness of a proper biopharmaceutical characterization of new drugs may result in drug molecules with a sufficiently high permeability, solubility and dissolution rate that will automatically increase the importance of BCS as a regulatory tool over time.
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| 6. |
- Neuhoff, Sibylle, et al.
(författare)
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Advantages and disadvantages of using bovine serum albumin and/or Cremophor EL as extracellular additives during transport studies of lipophilic compounds across Caco-2 monolayers
- 2007
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Ingår i: Journal of drug delivery science and technology. - 1773-2247. ; 17:4, s. 259-266
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Tidskriftsartikel (refereegranskat)abstract
- The effects of Cremophor EL (CEL) and bovine serum albumin (BSA) on the active and passive permeation of BCS class II compounds (felodipine, asimadoline) were studied across Caco-2 cells. The effect of BSA on either or both sides of the monolayers, apically applied CEL in the presence ofbasolateral BSA and the effect ofaddition of CEL on P-gp by the use ofquinidine were investigated. Presence of 4% BSA improved sink conditions and recovery from 60 to 95% for both felodipine and asimadoline. Efflux ratios obtained under comparable sink conditions, indicated that felodipine was transported by passive diffusion, while quinidine and asimadoline were transported actively. CEL decreased the transport rate for felodipine and asimadoline in the absorptive direction and increased in the secretory direction at different CEL concentrations, most likely due to the incorporation of drug into micelles. Our results indicate that inclusion of BSA is generally sufficient to increase the recovery for lipophilic BCS class II compounds. The overall effect of CEL on the permeability of a drug is compound specific and, therefore, less predictable and cannot be recommended.
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| 7. |
- Persson, Eva M., et al.
(författare)
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Is there an effect of food on the biliary secretion of cyclosporine and three in vivo formed metabolites in a porcine model?
- 2007
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Ingår i: Journal of Drug Delivery Science and Technology. - 1773-2247. ; 17:4, s. 253-258
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the effect of lipids and P-glycoprotein (P-gp) inhibition on the biliary secretion of cyclosporine (CsA) and in vivo formed metabolites in pigs. A parallel group design including 12 pigs in four groups and a combined single-pass intestinal perfusion and bile collection method was employed. CsA was perfused through the jejunum in an isotonic fluid alone and with verapamil or lipids added. The study showed that there was no difference between the administration groups, except for the fraction of the absorbed dose that was excreted in bile was twice as high when CsA was administered together with lipids. In conclusion, CsA is excreted via the biliary route in pigs without any significant involvement of P-gp. Concomitant food-intake could increase the secretion to the bile, presumably by prolonged associations between the CsA and the lipid species.
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| 8. |
- Reijmar, K., et al.
(författare)
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Bactericidal and hemolytic properties of mixed LL-37/surfactant systems
- 2007
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Ingår i: Journal of drug delivery science and technology. - 1773-2247. ; 17:4, s. 293-297
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between acyl chain homologues (C10 and C12) of n-acyl β-D-maltoside and the antimicrobial peptide LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) was investigated. Emphasis was placed on peptide-micelle complexation and its consequences for peptide proteolytic stability, as well as bactericidal and hemolytic effects of the mixed systems. From circular dichroism and liposome leakage experiments, it was found that LL-37 interacts with both surfactants investigated, and that this reduces the effective free peptide concentration. Analogously, LL-37 displayed increased proteolytic stability towards Pseudomonas aeruginosa elastase in surfactant solution. Despite this, conditions can be found at which the bactericidal effect of mixed peptide-surfactant systems is comparable to that of free LL-37. However, also a number of challenges to this type of antimicrobial peptide (AMP) carrier system were identified, notably related to reduction of bactericidal effect for some systems, and occurrence of hemolysis for mixed peptide-surfactant systems displaying advantageous bactericidal effects. Any use of such AMP carrier systems will therefore have to be carefully optimized in order to retain bactericidal activity and minimize toxicity.
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