Hydrolysis of Saturated Soybean Phosphatidylcholine in Aqueous Liposome Dispersions

Grit, Mustafa; Underberg, W.J.M.; Crommelin, Daan J.A.

doi:10.1002/jps.2600820405

Cited by 101 publications

(41 citation statements)

References 10 publications

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“…Chemically, phospholipid exhibits the maximum stability against hydrolysis at pH 6.5 which triggered the need of optimum pH for maximum EE. Therefore, gel formulations were adjusted to final pH of 7.4 for maximum %EE and biocompatibility with the physiological condition after topical application (Grit et al, 1993).…”

Section: Preparation and Characterizations Of El3-s80-loaded Gel Formmentioning

confidence: 99%

Optimized permeation enhancer for topical delivery of 5-fluorouracil-loaded elastic liposome using Design Expert: part II

et al. 2015

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Objective: To prepare and optimize the topical elastic liposome (EL)-loaded carbopol-980 gel of 5-Fluorouracil (5-FU) containing permeation enhancers (azone, propylene glycol (PG) and lauryl alcohol (LA)) and further evaluation for permeation flux of 5-FU, the activation energy and irritation in the rat skin. Methods: EL formulations were prepared using phosphatidylcholine and varied surfactants (Span 60, Span 80 and Tween-80) by rotator evaporation method and optimized by experimental design. In vitro characterizations dictated the EL containing Span 80 (lipid:surfactant ¼ 7:3) (EL3-S80) for further optimization of gel. Different gel formulations (5% w/w) with varying concentration (1-3%) of permeation enhancers were prepared and evaluated for viscosity, spreadability, the 5-FU permeation and deposition. The activation energy using the Franz diffusion cell and the plausible irritation using the Draize test were assessed on the albino rat and rabbit, respectively. Results and discussion: EL3-S80 was selected as an optimized EL owing to maximum desirability (0.99) and enhanced 5-FU flux (187.86 ± 14.1 mg/cm 2 /h). EL3-S80 suspension loaded gels (0.5%) revealed reduced viscosity leading to higher spreadability than blank gel. EL containing 3% azone in gel, EL containing 3% LA in gel and EL containing 3% PG in gel portrayed 187.86 ± 14.1, 117.7 ± 13.4 and 106.7 ± 7.3 mg/cm 2 /h as enhanced 5-FU flux values, respectively as compared to drug solution (8.8 ± 0.76 mg/cm 2 /h). Furthermore, reduced value of activation energy (2.63-folds) and the non-irritancy of gel could be effective and safe. Conclusion: ELA-3 gel formulation could be used as an effective and economic gel in cutaneous cancer and skin-related keratoses.

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Section: Preparation and Characterizations Of El3-s80-loaded Gel Formmentioning

confidence: 99%

Optimized permeation enhancer for topical delivery of 5-fluorouracil-loaded elastic liposome using Design Expert: part II

et al. 2015

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“…Thus, lipid hydrolysis is considered a critical parameter for the chemical stability of liposomal products. A considerable amount of research has been conducted on the factors that affect the hydrolysis rate, including pH and ionic strength of the storage solution (7)(8)(9). Because of these factors, the "assay of lipid components" and "degradation products related to the lipids" are recommended for pharmaceutical specifications in the draft guidance presented by the US FDA for liposomal products (10).…”

Section: Introductionmentioning

confidence: 99%

“…While unsaturated lipids may be analyzed by ultraviolet (UV) detection, saturated lipids, which are commonly used in liposomal formulations, have no specific absorbance in the UV region, and conventional UV detection cannot be used unless derivatized. Thus, the refractive index detector (RID), evaporative light-scattering detector (ELSD), charged aerosol detector (CAD), and MS were applied for the simultaneous HPLC analysis of lipids (8,(11)(12)(13). Since ELSDs are higher sensitivity than that exhibited by RIDs, compatible with gradient elution, more easily available than CAD, and simpler to maintain than LC-MS, they are widely used for lipid analyses.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination of Polyethylene Glycol-Conjugated Liposome Components by Using Reversed-Phase High-Performance Liquid Chromatography with UV and Evaporative Light Scattering Detection

2013

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Abstract. Liposomes incorporating polyethylene glycol (PEG)-conjugated lipids (PEGylated liposomes) have attracted attention as drug delivery carriers because they show good in vivo stability. The lipid component of PEGylated liposomal formulations needs to be quantified for quality control. In this study, a simple reversed-phase high-performance liquid chromatography (HPLC) method with an evaporative light-scattering detector (ELSD) was established for simultaneous determination of hydrogenated soy phosphatidylcholine, cholesterol, PEG-conjugated lipid, and hydrolysis products of phospholipid in PEGylated liposomal formulations. These lipids were separated using a C18 column with a gradient mobile phase consisting of ammonium acetate buffer and ammonium acetate in methanol at a flow rate of 1.0 ml/min. This method provided sufficient repeatability, linearity, and recovery rate for all lipids. However, the linearity and recovery rates of cholesterol achieved using a ultraviolet (UV) detector were better than those achieved using an ELSD. This validated method can be applied to assess the composition change during the preparation process of liposomes and to quantify lipid components and hydrolysis products contained in a commercially available liposomal formulation DOXIL®. Taken together, this reversed-phase HPLC-UV/ELSD method may be useful for the rapid or routine analysis of liposomal lipid components in process development and quality control.

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“…1) that limit the stability and useful shelf life of phospholipid-based pharmaceutical products such a liposomes, emulsions, and microemulsions (1)(2)(3)(4). The hydrolytic pathway of phosphatidylcholine (PC) involves base-catalyzed breakdown of two carboxy ester bonds.…”

Section: Introductionmentioning

confidence: 99%

“…The hydrolytic pathway of phosphatidylcholine (PC) involves base-catalyzed breakdown of two carboxy ester bonds. Lysophosphatidylcholine (LPC) is produced as the first intermediate product along with a free fatty acid (FFA) (2). A subsequent hydrolytic event releases glycerophosphorylcholine and a second fatty acid (Fig.…”

Section: Introductionmentioning

confidence: 99%

Simple Chromatographic Method for Simultaneous Analyses of Phosphatidylcholine, Lysophosphatidylcholine, and Free Fatty Acids

Mengesha

Bummer

2010

AAPS PharmSciTech

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Abstract. This study describes a simple chromatographic method for the simultaneous analyses of phosphatidylcholine (PC) and its hydrolytic degradation products: lysophosphatidylcholine (LPC) and free fatty acids (FFA). Quantitative determination of PC, LPC, and FFA is essential in order to assure safety and to accurately assess the shelf life of phospholipid-containing products. A single-run normalphase high-performance liquid chromatography (HPLC) with evaporative light scattering detector has been developed. The method utilizes an Allsphere silica analytical column and a gradient elution with mobile phases consisting of chloroform: chloroform-methanol (70:30%, v/v) and chloroform-methanolwater-ammonia (45:45:9.5:0.5%, v/v/v/v). The method adequately resolves PC, LPC, and FFA within a run time of 25 min. The quantitative analysis of PC and LPC has been achieved with external standard method. The free fatty acids were analyzed as a group using linoleic acid as representative standard. Linear calibration curves were obtained for PC (1.64-16.3 μg, r 2 =0.9991) and LPC (0.6-5.0 μg, r 2 = 0.9966), while a logarithmic calibration curve was obtained for linoleic acid (1.1-5.8 μg, r 2 =0.9967). The detection and quantification limits of LPC and FFA were 0.04 and 0.1 μg, respectively. As a means of validating the applicability of the assay to pharmaceutical products, PC liposome was subjected to alkaline hydrolytic degradation. Quantitative HPLC analysis showed that 97% of the total mass balance for PC could be accounted for in liposome formulation. The overall results show that the HPLC method could be a useful tool for chromatographic analysis, stability studies, and formulation characterization of phospholipid-based pharmaceuticals.

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Hydrolysis of Saturated Soybean Phosphatidylcholine in Aqueous Liposome Dispersions

Cited by 101 publications

References 10 publications

Optimized permeation enhancer for topical delivery of 5-fluorouracil-loaded elastic liposome using Design Expert: part II

Optimized permeation enhancer for topical delivery of 5-fluorouracil-loaded elastic liposome using Design Expert: part II

Simultaneous Determination of Polyethylene Glycol-Conjugated Liposome Components by Using Reversed-Phase High-Performance Liquid Chromatography with UV and Evaporative Light Scattering Detection

Simple Chromatographic Method for Simultaneous Analyses of Phosphatidylcholine, Lysophosphatidylcholine, and Free Fatty Acids

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