| 1. |
- Bramer, Tobias, et al.
(författare)
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Catanionic drug-surfactant mixtures : Phase behavior and sustained release from gels
- 2003
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Ingår i: Pharmaceutical research. - 0724-8741 .- 1573-904X. ; 20:10, s. 1661-1667
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study mixtures of SDS and the drugs diphenhydramine, tetracaine, and amitriptyline to compile phase diagrams and to investigate the use of interesting phases for sustained release from gels. METHODS: Phase diagrams were composed by studying large numbers of different compositions of negatively charged SDS and positively charged drug compounds visually, rheologically, and by cryotransmission electron microscopy. Drug release from Carbopol 940 and agar gels containing interesting phases, e.g., vesicle and branched micelle phases, was measured in vitro by the USP paddle method. RESULTS: Vesicles and elongated and branched micelles were formed on the SDS-rich side in all three systems examined. The tetracaine system differed from the other two in that it showed a vesicle area in the drug-rich side. Release of diphenhydramine from Carbopol 940 gels was slowed by at least a factor of 10 when in the form of vesicles or branched micelles. The same delay was found for both drug-rich and SDS-rich tetracaine vesicles. CONCLUSIONS: Mixtures of SDS and positively charged drugs form the same interesting phases as traditional catanionic mixtures. This may prove useful in obtaining functional controlled-release systems when using gels as drug carriers.
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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. |
- Dew, Noel, et al.
(författare)
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Gel formation in systems composed of drug containing catanionic vesicles and oppositely charged hydrophobically modified polymer.
- 2009
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Ingår i: Colloids and Surfaces B. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 70:2, s. 187-197
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to explore if mixtures of drug containing catanionic vesicles and polymers give rise to gel formation, and if so, if drug release from these gels could be prolonged. Catanionic vesicles formed from the drug substances alprenolol or tetracaine, and the oppositely charged surfactant sodium dodecyl sulphate were mixed with polymers. Three polymers with different properties were employed: one bearing hydrophobic modifications, one positively charged and one positively charged polymer bearing hydrophobic modifications. The structure of the vesicles before and after addition of polymer was investigated by using cryo-TEM. Gel formation was confirmed by using rheological measurements. Drug release was studied using a modified USP paddle method. Gels were observed to form only in the case when catanionic vesicles, most likely with a net negative charge, were mixed with positively charged polymer bearing lipophilic modifications. The release of drug substance from these systems, where the vesicles are not trapped within the gel but constitute a founding part of it, could be significantly prolonged. The drug release rate was found to depend on vesicle concentration to a higher extent than on polymer concentration.
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| 4. |
- Dew, Noel, 1980-, et al.
(författare)
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Gel formulations containing catanionic vesicles composed of alprenolol and SDS : effects of drug release and skin penetration on aggregate structure
- 2012
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Ingår i: Colloids and Surfaces B. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 89, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- To fully utilize the extended contact time of gel formulations a novel formulation with drug containing catanionic aggregates offering prolonged drug release and skin penetration were investigated. This study aimed to further explore the drug release process from catanionic vesicles in gels. Catanionic vesicles were formed from alprenolol and sodium dodecyl sulphate. Physical gels composed of catanionic vesicles and a SoftCAT polymer were used as well as covalent Carbopol gels. Drug release was measured in vitro using a modified USP paddle method and the skin penetration was studied using dermatomized pig ear skin mounted in horizontal Ussing chambers. The aggregate structure was visualized with cryo-TEM during the drug release and skin penetration process. The study results show that catanionic vesicles are present in the formulations throughout the drug release process and during the clinically relevant skin application time. Hence, the decreased skin penetration rate stems from the prolonged release of drug substance from the gels. The rheological investigation shows that the gel structure of the physically cross-linked gels is maintained even as the drug substance is released and the gel volume is decreased.These findings indicate that the applicability of formulations like these is a future possibility.
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| 5. |
- Berglin, Cecilia Engmer, et al.
(författare)
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Local treatment of the inner ear : A study of three different polymers aimed for middle ear administration
- 2015
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 135:10, s. 985-994
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion: A formulation based on sodium hyaluronate (NaHYA) was the most promising candidate vehicle for intra-tympanic drug administration regarding conductive hearing loss, inflammatory reactions, and elimination. Objectives: Recent advances in inner ear research support the idea of using the middle ear cavity for drug administration to target the inner ear. This paper presents rheological and safety assessments of three candidate polymer formulations for intra-tympanic drug administration. Method: The formulations were based on sodium carboxymethyl cellulose (NaCMC), sodium hyaluronate (NaHYA), and poloxamer 407 (POL). Rheological studies were performed with a controlled rate instrument of the couette type. Safety studies were performed in guinea pigs subjected to an intra-tympanic injection of the formulations. Hearing function was explored with ABR before and 1, 2, and 3 weeks after the injection. Elimination of the formulations marked with coal was explored with an endoscopic digital camera 1, 2, and 3 weeks after injection. Middle and inner ear morphology was examined with light microscopy 6 days after injection. Results: The results speak in favor of NaHYA, since it did not cause prolonged hearing threshold elevations. The results of the elimination and morphological investigations support the conclusion of NaHYA being the most promising candidate for intra-tympanic administration.
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| 6. |
- Berglin, Cecilia Engmér, et al.
(författare)
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Magnetic Resonance Imaging of the Middle and Inner Ear After Intratympanic Injection of a Gadolinium-Containing Gel
- 2014
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Ingår i: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 35:3, s. 526-532
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To investigate the distribution and elimination of a gadolinium containing high viscosity formulation of sodium hyaluronan (HYA gel) after injection to the middle ear.MATERIALS AND METHODS:The T1 contrast agent gadolinium-diethylenetriamine pentaacetic acid-bis methylamine (Gd-DTPA-BMA) was added to HYA gel and delivered to the middle ear of 13 albino guinea pigs by 3 different ways of injection. Magnetic resonance imaging was performed with a 4.7 T MRI system using a T1-weighted 3-dimentional rapid acquisition with relaxation enhancement sequence.RESULTS:An injection technique where the Gd-DTPA-BMA-containing HYA gel was delivered to the middle ear through a percutaneous injection through the auditory bulla after a small incision had been made in the tympanic membrane gave the best filling of the middle ear, covering the cochlea and the region of the round window niche for 24 hours in a majority of the ears studied. Ears injected without an incision in the tympanic membrane showed an immediate uptake of Gd-DTPA-BMA in the inner ear as a sign of rupture of the round window membrane.CONCLUSION:A percutaneous injection of a HYA gel into the tympanic bulla is distributed in a predictable way and gives a good filling of the middle ear cavity. The HYA gel remains in close vicinity to the RWM for more than 24 hours. Injection should be performed after an incision of the tympanic membrane has been made to prevent rupture of the round window membrane.
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| 7. |
- Berglin, Cecilia Engmer, et al.
(författare)
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Prevention of cisplatin-induced hearing loss by administration of a thiosulfate-containing gel to the middle ear in a guinea pig model
- 2011
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Ingår i: Cancer Chemotherapy and Pharmacology. - New York : Springer-Verlag New York. - 0344-5704 .- 1432-0843. ; 68:6, s. 1547-1556
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Tidskriftsartikel (refereegranskat)abstract
- Thiosulfate may reduce cisplatin-induced ototoxicity, most likely by relieving oxidative stress and by forming inactive platinum complexes. This study aimed to determine the concentration and protective effect of thiosulfate in the cochlea after application of a thiosulfate-containing high viscosity formulation of sodium hyaluronan (HYA gel) to the middle ear prior to i.v. injection of cisplatin in a guinea pig model. The release of thiosulfate (0.1 M) from HYA gel (0.5% w/w) was explored in vitro. Thiosulfate in the scala tympani perilymph of the cochlea 1 and 3 h after application of thiosulfate in HYA gel to the middle ear was quantified with HPLC and fluorescence detection. Thiosulfate in blood and CSF was also explored. The potential otoprotective effect was evaluated by hair cell count after treatment with thiosulfate in HYA gel applied to the middle ear 3 h prior to cisplatin injection (8 mg/kg b.w.). HYA did not impede the release of thiosulfate. Middle ear administration of thiosulfate in HYA gel gave high concentrations in the scala tympani perilymph while maintaining low levels in blood, and it protected against cisplatin-induced hair cell loss. HYA gel is an effective vehicle for administration of thiosulfate to the middle ear. Local application of a thiosulfate-containing HYA gel reduces the ototoxicity of cisplatin most likely without compromising its antineoplastic effect. This provides a minimally invasive protective treatment that can easily be repeated if necessary.
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| 8. |
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| 9. |
- Bramer, Tobias, et al.
(författare)
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Implications of regular solution theory on the release mechanism of catanionic mixtures from gels
- 2009
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Ingår i: Colloids and Surfaces B. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 71:2, s. 214-225
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to apply the regular solution theory of mixed micelles to gain new insights on the drug release mechanism, when using catanionic mixtures as a method of obtaining prolonged release from gels. Synergistic effects were investigated at equilibrium and quantified in terms of regular solution theory interaction parameters. The drug release from catanionic aggregates was studied both in a polymer free environment, using dialysis membranes, and in gels, using a modified LISP paddle method. The drug release kinetics was modelled theoretically by combining the regular solution theory with Fick's diffusion laws assuming a contribution to the transport only from monomeric species (stationary aggregates). The theoretical predictions were found to be in reasonably good agreement with experiments. An analysis of the calculated distribution of species between aggregated and monomeric states was shown to provide further insights into the release mechanism.
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| 10. |
- Bramer, Tobias, et al.
(författare)
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Pharmaceutical applications for catanionic mixtures
- 2007
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 59:10, s. 1319-1334
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Forskningsöversikt (refereegranskat)abstract
- Mixtures of oppositely charged surfactants, so called catanionic mixtures, are a growing area of research. These mixtures have been shown to form several different types of surfactant aggregates, such as micelles of various forms and sizes, and lamellar structures, such as vesicles. In this review, a short introduction to the field of catanionic mixtures is presented and the pharmaceutical possibilities offered by such mixtures are reviewed. There are several interesting ideas on how to apply catanionic mixtures to improve the delivery of, for example, drug compounds and DNA, or for HIV treatment.
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