Aqueous solubility of diclofenac diethylamine in the presence of pharmaceutical additives: A comparative study with diclofenac sodium

Citation
E. Khalil et al., Aqueous solubility of diclofenac diethylamine in the presence of pharmaceutical additives: A comparative study with diclofenac sodium, DRUG DEV IN, 26(4), 2000, pp. 375-381
Citations number
18
Categorie Soggetti
Pharmacology & Toxicology
Journal title
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
ISSN journal
03639045 → ACNP
Volume
26
Issue
4
Year of publication
2000
Pages
375 - 381
Database
ISI
SICI code
0363-9045(2000)26:4<375:ASODDI>2.0.ZU;2-M
Abstract
Aqueous solubility of diclofenac diethylamine (DDEA), a nonsteroidal anti-i nflammatory drug currently formulated as a topical emulgel, was studied in the presence of pharmaceutical additives and compared with diclofenac sodiu m (DS). Electrolytes at low concentrations exhibited a salting-in effect on DDEA with peak solubility that was attributed to the association of DDEA i nto micelles, followed by a salting-out effect at higher concentrations, by which structure formation by DDEA molecules increased and precipitation oc curred. For DS, which is nor capable of forming micelles, the salting-our e ffect was dominant due to the common ion effect. Cosolvents displayed signi ficant enhancement in solubility of both salts except glycerol, which showe d a slight increase in solubility, of DDEA and a decrease in solubility of DS due to transformation into the less soluble hydrate form. Ethanol and po lyethylene glycol (PEG) 400 cosolvent systems at all concentrations showed positive deviations from the log-linens solubility equation. In the case of propylene glycol (PG) cosolvent systems, negative deviations were observed at low volume fractions of cosolvent, while positive deviations were obser ved at high volume fractions of cosolvent for DS and DDEA. The parent drug, being less ionizable and highly nonpolar, showed negative deviations Ltp t o 90% PG content. Thus, the positive deviations for DS and DDEA could be at tributed to the more ionizable carboxylic group and its higher ability for hydrogen bonding at higher fractions of cosolvent. Polyvinylprrolidone (PVP ) and PEG4000 or PEG6000 enhanced rite solubility of DS and DDEA, with PVP exerting higher solubility: efficiency and DS showing better solubility tha n DDEA. Solubilities of DS in Tween 80 (T80) and Pluronic F-127 (PF127) aqu eous solutions were almost similar, while the solubility of DDEA in the pre sence of T80 was higher than the solubility in the presence of PF127. DS ap peared ro be located more in the polyoxyethylene mantle of the micelles, wh ile DDEA was located more in the core of the micelles.