Influence of a charged phospholipid on the release pattern of timolol maleate from cubic liquid crystalline phases

Abstract

The release of timolol maleate, a drug for treatment of glaucoma, from cubic liquid crystals consisting of charged and uncharged lipids was investigated in vitro. It was shown that the release of drug was dependent on the ionic strength of the receptor medium and the relative amount of a charged phospholipid in the cubic phase. In the absence of charged lipids, the release of timolol was complete, irrespective of the medium used, i.e. distilled water or saline solution. In the presence of a negatively charged phospholipid, diacylphosphatidylglycerol, the release of drug from the cubic phase was incomplete when distilled water was the receptor medium. The residual drug was dependent on the amount of charged lipid in the cubic phase. In saline solution, on the other hand, all of the drug was released. The results are interpreted as an effect of electrostatic attraction between the positively charged drug with the negatively charged bilayer surface, which is screened in the presence of saline. The possible influence of the cubic geometry is discussed as well. This work shows that lipids offer many possibilities in the formulation of sustained drug release systems.

Steric Stabilizers for Cubic Phase Lyotropic Liquid Crystal Nanodispersions (Cubosomes)

“…A further element of consideration for cubosomes is their high internal interfacial area, which may lead to stabilizer sequestration within the liquid crystalline nanostructure, which will reduce its contribution to colloidal stability [120]. Although a charged stabilizer can be applied to provide an electrostatic barrier to the flocculation of cubosomes, it is more common to utilize a steric stabilizer, as charged surfactant molecules have a high propensity to disrupt the internal phase structure of cubosomes [121]. Charged nanostructured particles, such as negatively charged liposomes, have also been reported to have a shorter half-life in the blood than neutral liposomes [122,123] and positively charged liposomes were found to be toxic and quickly removed from systemic circulation [124].…”

An injectable liquid crystal system for sustained delivery of entecavir

“…Adding anionic phospholipids or cationic surfactants as an anchoring material were studied previously. The charge interaction between a charged drug and an oppositely charged anchoring material showed enhanced loading and prolonged release properties (Lindell et al, 1998;Lynch et al, 2003). These in vitro studies provided theoretical demonstrations of functionalizing LCs.…”

Self-Assembling Lipid Formulations

“…As lipids are amphiphilic in nature, their solutions and LC phases are typically relatively good solvents by themselves. This property has been demonstrated for a wide range of drug substances such as: acetylsalicylic acid, diclofenac sodium, hydrochlorquine sulfate, and vitamin E [ 7 ] ; propantheline bromide and oxybutynin hydrochloride [ 8 ] ; timolol maleate [ 9 ] ; chlorpheniramine maleate and propanolol hydrochloride [ 10 ] ; melatonin, pindolol, propanolol and primethamine [ 11 ] ; haemoglobin [ 12 ] ; cefazolin [ 13 ] ; and insulin [ 14,15 ] . The vast majority of these studies feature the GMO water system, forming the bi-continuous V 2 phase at relevant temperatures (see Fig.…”