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| 2. |
- 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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| 3. |
- Dew, Noel, et al.
(författare)
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Catanionic aggregates formed from drugs and lauric or capric acids enable prolonged release from gels
- 2008
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 323:2, s. 386-394
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to add to the range of charged surfactants that can be used to form catanionic aggregates with oppositely charged surface active drug substances, and to apply these aggregates to prolong drug release from gels. The surfactants used in this study, lauric and capric acids are of natural origin-unlike traditionally used, synthetic, surfactants. The mixtures of drug substances and oppositely charged surfactants were studied visually and with cryogenic transmission electron microscopy. Drug release from gels was studied with a modified USP paddle method. This study shows that lauric and capric acids are as, or even more, active in forming catanionic aggregates than traditionally used surfactants such as sodium dodecyl sulfate. It is shown that the length of the hydrophobic part of the surfactant plays an important role in the formation of pharmaceutically interesting catanionic aggregates. As seen in previous studies, using catanionic vesicles prolongs the drug release from gels and decreases the apparent diffusion coefficient by a factor of 10-50, compared to a gel containing only drug substance.
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| 4. |
- Dew, Noel, 1980-
(författare)
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Catanionic Aggregates in Gels : Prolonged Drug Release and Potential Implications for Topical Use
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gels are popular dosage forms. This topical dosage form may be advantageous compared to oral or parenteral dosage forms. Favorable rheological or bioadhesive properties of gels might provide extended contact times at the site of administration compared to aqueous solutions. However, due to the high water content of gels, these are usually quickly emptied of the drug substance. One way of prolonging the drug release from gels is to contain the drug substance in catanionic aggregates in the gel. These aggregates are formed in solutions of oppositely charged surfactants and a drug can be used instead of one of the surfactants. In this thesis catanionic aggregates composed of drug substances and oppositely charged surfactants were studied and the possibility to use these aggregates for the purpose of prolonged drug release was investigated. The formation of catanionic aggregates when using drugs was found to be a common occurrence in addition to which, the oppositely charged surfactant can be varied and surfactants of natural origin with a low toxicity were used. Most combinations tested rendered either vesicles or elongated micelles. When the catanionic aggregates were contained in gels the drug release was substantially prolonged. The apparent diffusion coefficients were lowered 10-100 times compared to the reference gels. When gels with catanionic vesicles with substantial prolonged drug release were applied to skin the penetration rate was lowered extensively. No morphological differences were observed between skin samples that had been exposed to formulations containing catanionic aggregates and skin samples exposed to saline solution, air or formulations containing only the drug. Both conventional, covalently linked pre-formed gels and physical gels, where the catanionic vesicles form the cross-links upon interaction with the polymer, can be used for these purposes. When the effect of drug release on aggregate structure was studied, it was shown that vesicles are present in both conventional and physical gels throughout the drug release process. This thesis shows that catanionic aggregates contained in gels can present an advantageous formulation strategy to prolong the drug release, thereby improving the efficiency of gel formulations.
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| 5. |
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Dew, Noel, 1980-, et al.
(författare)
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Novel Gel Formulations with Catanionic Aggregates Enable Prolonged Drug Release and Reduced Skin Permeation
- 2011
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 63:10, s. 1265-1273
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to investigate skin permeation rates of a drug substance when applied in novel gel formulations with catanionic aggregates. Methods: Reference gel without catanionic aggregates was compared with formulations with catanionic aggregates composed of tetracaine and either sodium dodecyl sulphate (SDS) or capric acid. Carbomer and SoftCAT were used to compare the effect of different gel types to elucidate if physically cross-linked, 'self-destructing' systems had benefits compared with classical, covalently cross-linked, gels. Key findings: The rheological investigation showed that the interactions between the SoftCAT polymer and tetracaine/SDS aggregates were stronger than when the tetracaine/capric acid aggregates were used. The skin permeation was measured ex vivo in horizontal Ussing chambers and the permeation of tetracaine was significantly lower when formulations with tetracaine/SDS aggregates were applied (P < 0.001), but not statistically different from the reference when capric acid was used. Conclusions: No morphological differences could be distinguished between the skin samples exposed to the different formulations or the reference. Skin permeation was compared with silicone sheet permeation and the results indicated that silicone sheets could be used as a model of skin when using these formulations.
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