PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9876510

Interactions between lonidamine and beta- or hydroxypropyl-beta-cyclodextrin.

G F Palmieri·P Wehrlé·S Martelli
View original source ↗Export metadata ↓

Abstract

The possibility of obtaining inclusion complexes between lonidamine and beta- or hydroxypropyl-beta-cyclodextrin have been evaluated by phase solubility diagram, differential scanning calorimetry (DSC), and x-ray diffractometry. The applied complexation methods were spray-drying, kneading, and solid dispersion. DSC and x-ray analyses of the powders revealed an external interaction between lonidamine and cyclodextrins. Dissolution profiles of the obtained powders were also studied to define the most appropriate preparation method and molar ratio to use in attempts to increase lonidamine water solubility.

Explore related subjects

2-Hydroxypropyl-beta-cyclodextrinAntineoplastic AgentsCalorimetry, Differential ScanningCyclodextrinsDrug InteractionsIndazolesSolubilityWaterX-Ray Diffractionbeta-CyclodextrinsJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

G F Palmieri, P Wehrlé, S Martelli. 1998. Interactions between lonidamine and beta- or hydroxypropyl-beta-cyclodextrin.. https://doi.org/10.3109/03639049809082367

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2002

Effect of acute and chronic administration of the selective 5-HT2C receptor antagonist SB-243213 on midbrain dopamine neurons in the rat: an in vivo extracellular single cell study.

In this study, we examined the effect of the acute and chronic administration of the selective 5-HT2C receptor antagonist SB-243213 (SB) on the activity of spontaneously active dopamine (DA) cells in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) in anesthetized, albino, male Sprague-Dawley rats. This was accomplished using the technique of in vivo extracellular single cell recording. The acute i.v. administration of SB-243213 (0.025-3.2 mg/kg) did not significantly alter the basal firing rate or pattern of either spontaneously active SNC or VTA DA neurons compared to vehicle-treated controls. The acute i.p. administration of either 1 or 10 mg/kg of SB-243213 did not significantly alter the number of spontaneously active DA cells in the SNC or VTA compared to vehicle-treated controls, whereas the 3 mg/kg dose only significantly decreased the number of spontaneously active VTA DA neurons. Overall, the 1 mg/kg dose of SB-243213 did not significantly alter the firing pattern of either SNC or VTA DA neurons compared to vehicle-treated controls. In contrast, the 3 mg/kg dose significantly altered the firing pattern of SNC DA neurons, whereas the 10 mg/kg dose altered the firing pattern of DA neurons in both the SNC and VTA. The repeated i.p. administration (21 days) of 1, 3, and 10 mg/kg of SB-243213 or 20 mg/kg of clozapine produced a significant decrease in the number of spontaneously active DA cells in the VTA compared to vehicle-treated controls. The decrease in the number of spontaneously active VTA DA cells was not reversed by the i.v. administration of (+)-apomorphine (50 microg/kg). The repeated administration of either 1 or 3 mg/kg of SB-243213 had minimal effects on the firing pattern of either SNC or VTA DA neurons. In contrast, the firing pattern of VTA DA neurons was significantly altered by 10 mg/kg dose of SB-243213. Overall, our results indicate that antagonism of the 5-HT2C receptor alters the activity of midbrain DA neurons in anesthetized rats and suggest that SB-243213 has an atypical antipsychotic profile following chronic administration.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2002

The effects of water-soluble cyclodextrins on the histological integrity of the rat nasal mucosa.

The aim of this study was to investigate the effect of highly water-soluble cyclodextrins (CDs) on the histological integrity of the nasal mucosa. In order to evaluate their effects, the in vivo single and repeated nasal exposure studies were performed using male Wistar rats. The rat nasal cavity was excised after an application of various CD solutions at different times. The morphological appearances of the rat nasal mucosae were analyzed with the light microscopic and the scanning electron microscopic studies. By utilizing 5-min exposure of each CD solution to the nasal mucosa, no tissue damage was visible for 1.5% w/v beta-CD and 5 and 20% w/v hydroxypropyl beta-CD (HP beta-CD), and the effects were quite similar to controls. However, using 20% w/v randomly methylated beta-CD (RM beta-CD) showed severe damage on the integrity of nasal mucosa. The severity was similar to 1% w/v polyoxyethylene-9-lauryl ether or l% w/v sodium deoxycholate. Meanwhile, 30 or 60 min exposure to 10% w/v HP beta-CD or RM beta-CD resulted in no obvious mucosal damage. In addition, in vivo repeated dosing of RM beta-CD did not show any toxicity up to 20% w/v. These results suggest that at least, less than 10% w/v CD solutions do not induce gross tissue damage and can keep the histological integrity of the nasal mucosa.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2002

Common solubilizers to estimate the Caco-2 transport of poorly water-soluble drugs.

Solubilizers are often used to enhance the bioavailability of drugs with poor aqueous solubility. This study focuses on the use of the Caco-2 system containing solubilizers to predict the absorption of poorly water-soluble drugs in humans. First, the effects of propylene glycol (PG), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), polyethylene glycol 400 (PEG 400), and Tween 80 on the viability (transepithelial electrical resistance, TEER) of 3-day cultured Caco-2 monolayers were evaluated. These solubilizers, even at the low concentration, reduce the viability of Caco-2 monolayers; these results indicate the impossibility for 3-day cultured Caco-2 monolayers to be used for this test. Next, the effects of PG, Tween 80, PEG 400, HP-beta-CD, Pluronic F-68 (Pluronic), HCO-40, sodium lauryl sulfate (SLS), Gelucire 44/14, Transcutol P, and extract gall powder on the viability of 21-day cultured Caco-2 monolayers and the apparent permeability (P(app)) of propranolol (PPL), Nadolol (NDL), and FITC-dextran 4000 (FD-4) were investigated. Five different solubilizing methods (20% PG, 5% Tween 80, 5% PEG 400, 5% HP-beta-CD, and 5% Tween 80+5% PEG 400) did not affect the viability of 21-day cultured Caco-2 monolayers. Furthermore, the P(app) values of the three compounds containing these solubilizers did not differ from the values for control formulations (without solubilizers). These results clearly suggest that the use of PG, Tween 80, PEG 400, or HP-beta-CD as solubilizing excipients and the testing of these formulations on 21-day cultured Caco-2 monolayers can predict intestinal absorption of poorly water-soluble drugs in humans.

2-Hydroxypropyl-beta-cyclodextrin↗