Comparative interaction of 2-hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin with itraconazole: Phase-solubility behavior and stabilization of supersaturated drug solutions (original) (raw)
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Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs
Brazilian Journal of Pharmaceutical Sciences, 2011
Cyclodextrins (CDs) are cyclic oligosaccharides composed of D-glucopyranoside units linked by glycosidic bonds. Their main property is the ability to modify the physicochemical and biological characteristics of low-soluble drugs through the formation of drug:CD inclusion complexes. Inclusion complexation requires that host molecules fit completely or partially within the CD cavity. This adjustment is directly related to the physicochemical properties of the guest and host molecules, easy accommodation of guest molecules within the CD cavity, stoichiometry, therapeutic dose, and toxicity. However, dosage forms may achieve a high volume, depending on the amount of CD required. Thus, it is necessary to increase solubilization efficiency in order to use smaller amounts of CD. This can be achieved by adding small amounts of water-soluble polymers to the system. This review addresses aspects related to drug complexation with CDs using water-soluble polymers to optimize the amount of CD us...
2015
The main objective of this study was to investigate different manufacturing processes claimed to promote inclusion complexation between different drugs and cyclodextrins (econazole and α-cyclodextrin; indomethacin and methyl-β-cyclodextrin; olanzapine and methyl-β-cyclodextrin; flurbiprofen and methyl-β-cyclodextrin) in order to enhance the apparent solubility and dissolution properties of drugs. Specifically, the effectiveness of supercritical carbon dioxide processing for the preparation of solid drug-cyclodextrin inclusion complexes was investigated and compared to other preparation methods. Nitrate, besylate, sulfosalicylate dihydrate and maleate salts of econazole were synthesised. The solid drug-cyclodextrin inclusion complexes were prepared by physical mixing, freeze drying from aqueous solution and processing with supercritical carbon dioxide. The complexes were evaluated by scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, 1H-nuclear...
Solubility of Cyclodextrins and Drug/Cyclodextrin Complexes
Molecules
Cyclodextrins (CDs), a group of oligosaccharides formed by glucose units bound together in a ring, show a promising ability to form complexes with drug molecules and improve their physicochemical properties without molecular modifications. The stoichiometry of drug/CD complexes is most frequently 1:1. However, natural CDs have a tendency to self-assemble and form aggregates in aqueous media. CD aggregation can limit their solubility. Through derivative formation, it is possible to enhance their solubility and complexation capacity, but this depends on the type of substituent and degree of substitution. Formation of water-soluble drug/CD complexes can increase drug permeation through biological membranes. To maximize drug permeation the amount of added CD into pharmaceutical preparation has to be optimized. However, solubility of CDs, especially that of natural CDs, is affected by the complex formation. The presence of pharmaceutical excipients, such as water-soluble polymers, preservatives, and surfactants, can influence the solubilizing abilities of CDs, but this depends on the excipients' physicochemical properties. The competitive CD complexation of drugs and excipients has to be considered during formulation studies.
CYCLODEXTRIN AS SOLUBILIZER AND TARGETING AGENT FOR DRUGS
International Journal of Applied Pharmaceutics, 2024
Natural cyclic oligosaccharides called cyclodextrins (CDs) improve the bioavailability of drugs by the formation of inclusion complexes involving small and macromolecules of poorly soluble compounds in water. CDs act as a solubilizer and targeting agent for drugs with low water solubility, enabling them to effectively target specific cells. Where poorly water-soluble compounds interact with the hydrophobic cavity of CDs to enhance their solubility. CDs are effective drug delivery agents because of their essential function as processing complex carriers. Various ligands can be utilized to modify the surface of cyclodextrin to actively target drugs. It is possible to consider it to have amphiphilic characteristics by enduring a chemical transformation with long aliphatic chains, and a variety of amphiphilic CDs can produce nanoparticles without the usage of surfactants. CD-nanocarriersact as cargo with solubilizers for drugs and a targeting agent for specific receptors present in specific cells and release the drug. CDs have many applications, including the reduction of drug-induced gastrointestinal discomfort, avoiding interactions between drug-drug and drugexcipient, and transforming drug products that are liquid into microcrystalline solid powders. Because of their biocompatibility and biodegradability, CDs have outstanding properties that make them particularly useful in the pharmaceutical and cosmetic industries.
Dissolution Enhancement of a Poorly Water-Soluble Drug Using Cyclodextrin as Water-Soluble Carriers
International Journal of Pharmacology and Pharmaceutical Sciences
Cyclodextrin are the functional excipients which are useful for enhancing solubility, and are being used in an increasing way to overcome the undesirable pharmaceutical characteristics especially poor aqueous solubility. It has generally been assumed that mechanism where cyclodextrin exert their effects, especially their augmentation of solubility is via the formation of non-covalent dynamic inclusion complexes. The aim of this study was to prepare and characterization of atenolol-cyclodextrin(CDs) complex. Atenolol (ATN) is widely use as anti-hypertensive drug (beta blocker) it oral bioavailability is 46-60% such low bioavailability has been attributed to low aqueous solubility of atenolol. To increase its aqueous solubility two different type of cyclodextrins (CDs): beta Cyclodextrin (BCD) and hydroxy-propyl beta cyclodextrin (HPBCD) were used. Solubility depends on the type of CDs, increased solubility were obtained. When the more substituted CDs (HPBCD) were used instead of non-...
Effect of Cyclodextrin Types and Co-Solvent on Solubility of a Poorly Water Soluble Drug
Scientia Pharmaceutica
The aim of the study was to investigate the solubility of piroxicam (Prx) depending on the inclusion complexation with various cyclodextrins (CDs) and on ethanol as a co-solvent. The phase-solubility method was applied to determine drug solubility in binary and ternary systems. The results showed that in systems consisting of the drug dissolved in ethanol-water mixtures, the drug solubility increased exponentially with a rising concentration of ethanol. The phase solubility measurements of the drug in aqueous solutions of CDs, β-CD and γ-CD exhibited diagrams of A L-type, whereas 2,6-dimethyl-β-CD revealed A P-type. The destabilizing effect of ethanol as a co-solvent was observed for all complexes regardless of the CD type, as a consequence of it the lowering of the complex formation constants. In systems with a higher concentration of ethanol, the drug solubility was increased in opposition to the decreasing complex formation constants. According to this study, the type of CDs played a more important role on the solubility of Prx, and the use of ethanol as a co-solvent exhibited no synergistic effect on the improvement of Prx solubility. The Prx solubility was increased again due to the better solubility in ethanol.
Effect of self-aggregation of γ-cyclodextrin on drug solubilization
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2010
The purpose of this study was to investigate the physicochemical properties of drug-saturated aqueous cyclodextrin (CD) solutions. Phase solubility profiles of different drugs were determined in aqueous solutions containing c-cyclodextrin (cCD) and/or hydroxypropyl-ccyclodextrin (HPcCD) in absence or presence of watersoluble polymers. 1 H-NMR and turbidity analysis were performed as well as permeation studies. Phase solubility diagrams showed that the observed cCD content (1-20% w/v) was only slightly different from the theoretical values for aqueous solutions that had been saturated with indomethacin, diclofenac sodium or amphotericin B, all displayed A-type profiles, while it was less than the theoretical value in solutions that had been saturated with corticosteroids (hydrocortisone and dexamethasone) that displayed B S -type profiles. In the latter case self-assemble of drug/CD complexes decreased the overall CD solubility. Water-soluble polymers enhanced aqueous solubility of the drugs tested by stabilizing the drug/CD complexes, i.e. enhancing their stability constants, without affecting the observed aqueous cCD solubility. When the drug solubility leveled off (the B S -type profiles) the amount of dissolved cCD increased and approached the theoretical values. Hydrocortisone formed partial inclusion complex with cCD and HPcCD and no non-inclusion or aggregates could be detected in diluted solutions by 1 H-NMR. Both permeation and turbidity studies showed that formation of dexamethasone/cCD complex promoted CD aggregation. All these observations indicate that CD aggregate formations play a role in CD solubilization of lipophilic and poorly water-soluble drugs and that the water-soluble polymers enhance the complexation efficiency of cCD and HPcCD by stabilizing the self-assembled drug/CD nanoparticles and promote non-inclusion complex formation.
The effects of organic salts on the cyclodextrin solubilization of drugs
International Journal of Pharmaceutics, 2003
Previous studies have indicated that conventional description of drug/cyclodextrin complexes in aqueous solutions as inclusion complexes are not as unambiguous as one might think. It has been shown that in some cases drug/cyclodextrin complexes consist of a mixture of inclusion and non-inclusion complexes. Furthermore it has been shown that drug/cyclodextrin complexes can form aggregates containing up to couple of hundred complexes. In this present study -cyclodextrin (CD) solubilization of hydrocortisone is enhanced by including short-chain anionic and cationic species in the aqueous complexation medium. For example, maximum hydrocortisone solubility in pure aqueous CD solutions or suspensions is 2.2 mg/ml. Addition of 1% (w/v) sodium acetate to the complexation medium increases this value to 7.1 mg/ml (or over 220%). Further addition of 0.25% (w/v) hydroxypropyl methylcellulose to the medium increased the hydrocortisone solubility to over 9 mg/ml. Similar results were obtained when sodium salicylate or benzalkonium chloride were added to the complexation medium. It is also shown that cyclodextrin complexes of lipophilic compounds that have good affinity for the cyclodextrin cavity can be used to enhance cyclodextrin solubilization of drugs that have low affinity for the cavity. All these observations can be explained by formation of drug/cyclodextrin complex aggregates.