Dissolution enhancers cyclodextrins

J Pitha, J Pitha. Amorphous water-soluble derivatives of cyclodextrins. Nontoxic dissolution-enhancing excipients. J Pharm Sci 74 987-990, 1985. 

Hirai, S. Formulation studies of cefotiam hexetil hydrochloride effect of a-cyclodextrin as dissolution enhancer. Proceedings of 7th International Symposium on Cyclodextrins. Osa, T., Ed. Komiyama Printing Co., Ltd. Tokyo, 1994 39-44. 

Beta-cyclodextrin Complexing agent, dissolution enhancer, stabilizer... 

Zheng, Y. Xuan, X. P. Wang, J. J. Fan, M. H. The enhanced dissolution P-cyclodextrin in some hydrophilic ionic liquids. /. Phys. Chem. A, 114, 3926-3931. 

Certain surface-active compounds [499], when dissolved in water under conditions of saturation, form self-associated aggregates [39,486-488] or micelles [39,485], which can interfere with the determination of the true aqueous solubility and the pKa of the compound. When the compounds are very sparingly soluble in water, additives can be used to enhance the rate of dissolution [494,495], One can consider DMSO used in this sense. However, the presence of these solvents can in some cases interfere with the determination of the true aqueous solubility. If measurements are done in the presence of simple surfactants [500], bile salts [501], complexing agents such as cyclodextrins [489 191,493], or ion-pair-forming counterions [492], extensive considerations need to be applied in attempting to extract the true aqueous solubility from the data. Such corrective measures are described below. 

The bioavailability of silibinin from the extract is low and seems to depend on several factors such as (i) the content of accompanying substances with a solubilizing character such as other flavonoids, phenol derivatives, aminoacids, proteins, tocopherol, fat, cholesterol, and others found in the extract and (ii) the concentration of the extract itself (132,133). The systemic bioavailability can be enhanced by adding solubilizing substances to the extract (11,134). The bioavailability of silibinin can also be enhanced by the complexation with phosphatidylcholine or p-cyclodextrin, and possibly by the choice of the capsule material (135-137). The variations in content, dissolution, and (oral) bioavailability of silibinin between different commercially available silymarin products—despite the same declaration of content—are significant (138). 

Nagarsenker, M. S., R. N. Meshram, and G. Ramprakash (2000). Solid dispersion of hydroxypropyl-fi-cyclodextrin and ketorolac enhancement iofvitro dissolution rates, improvement in antiin ammatory activity and reduction in ulcerogenicity in rdtfharm. Pharmacol., 52 949-956. 

Consequently, absorption enhancers were used in dry powder and liquid formulations to enhance the pulmonary absorption of SCT. Without absorption enhancers, SCT absorption from dry powder or solution was similar to that observed after intratracheal administration. However, the absorption was more improved from dry powder than from solution when absorption enhancers (oleic acid, lecithin, citric acid, taurocholic acid, dimethyl-[5-cyclodextrin, octyl-P-D-glu-coside) were co-administered intratracheally. Such improved absorption could be due to the fact that enhancers added to the dry powder dissolved at high concentration because only a trace volume of fluid lining the alveolar epithelium was available for their dissolution. However, the potential implications of such a mechanism on lung toxicity, especially in lung edema, is yet to be investigated in detail [68]. 

The highly water-soluble 2-hydroxypropyl-/i-cyclodextrin (2-HP-/1-CD) is a commercially useful general complexing agent. Inclusion complexes of poorly water-soluble Naproxen with 2-HP-/1-CD were useful to increase its solubility and dissolution rate, and resulted in an enhancement of bio-availability and minimized the gastrointestinal toxicity of the drug [69]. The water solubility of melatonin, which is an indole amide neurohormone, was also enhanced in a complex with 2-HP-/J-CD [70]. 

Cyclodextrins may be used to form inclusion complexes with a variety of drug molecules, resulting primarily in improvements to dissolution and bioavailability owing to enhanced solubility and improved chemical and physical stability see Section 18. 

Uekama, K., Horiuchi, Y., Kikuchi, M., et al. (1988) Enhanced dissolution and oral bioavailability of a-tocopheryl esters by dimethyl-P-cyclodextrin complexations. J. Incl. Phenom. 6 167-174. 

McCray JE, Brusseau ML. (1999). Cyclodextrin enhanced in situ flushing of multiple-component immiscible organic liquid contamination at the field scale Analysis of dissolution behavior. Environmental Science and Technology 33 89-95. 

Ghorab, M.K. Adeyeye, M.C. Enhancement of ibuprofen dissolution via wet granulation with -cyclodextrin. Pharm. Develop, and Technology 2001, 6 (3), 303-312. 

ABSTRACT Fendiline hydrochloride [N-/1-phenylethyl/-3 9 3-diphenylpropylamine.HC is a sparingly soluble and hardly absorbable coronary vasodilator The fendiline base forms complex ivith /3-cyclodextrin in a molar ratio of 1 2 The enhanced solubility and dissolution rate of the complex resulted in a better bioavailability of the drug,... 

Cinnarizine(CN), [1 -(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine] one of cerebral blood flow improvers, is widely used orally for treatment of cerebral apoplexy, cerebral arteriosclerosis and post traumatic cerebral sympton. However, CN, a weak base of pKa 7.47(1), is slightly soluble in water, as the solubility is less than 10 mg/ml at 37°C. Accordingly, it was less absorbed in patients of achlorhydria. This study, therefore, was attenpted to apply cyclodextrin conplexation to an enhancement of the solubility, dissolution rate, and bioavailability of CN. 

There are numerous examples of medicinal products in which dissolution rate enhancing technologies are applied to increase the bioavailabiUty or absorption rate of an active substance. Cardiac glycosides should be given as micronised particles in a solid oral dosage form because otherwise their dissolution rate and hence their bioavaUability is too low. Piroxicam was shown to be absorbed faster when given as a cyclodextrin complex, which increases the dissolution rate. Similarly, the bioavailabiUty of albendazole as a cyclodextrin complex was increased compared to crystalline non-complexed albendazole, based on the same mechanism. And finally, the bioavailabiUty of amorphous chloramphenicol is higher than that of crystalline chloramphenicol. 

Celecoxib HP-P-CD PVP, HPMC, PEG Kneading Water containing 1% sodium lauryl sulphate Upon addition of water-soluble polymers, increased solubilization strength of cyclodextrins and apparent stability constants of systems along with marked enhancement in dissolution rate [67]... 

T. Taupitz, J.B. Dressman, C.M. Buchanan, and S. Klein, Cyclodextrin-water soluble polymer ternary complexes enhance the solubility and dissolution behaviour of poorly soluble drugs. Case example Itraconazole, Eur. J. Pharm. Biopharm., 83,378-387, 2013. 

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