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Abstract
Vesicular delivery systems such as liposomes and niosomes have been reported to serve as a local depot for the sustained release of drugs. Also, lipid based formulations such as lipospheres have evoked a considerable interest in the past few years. The purpose of this study was to formulate a controlled release topically effective drug delivery system for aceclofenac (a non steroidal anti-inflammatory drug) utilizing the aforementioned vesicular delivery systems and lipospheres to overcome the side effects resulting from the oral administration of the drug. Lipid film hydration method was used to prepare aceclofenac multilamellar liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) with or without charge inducers and multilamellar niosomes prepared from Span 40 or Span 60 and (CH). PC:CH and Span:CH were utilized in the preparation of the vesicles at three molar ratios, viz: 7:4, 7:6 and 7:7. A comparative study was done between liposomes and niosomes through evaluation of entrapment efficiency, particle size, shape, differential scanning calorimetry and in vitro drug release. Stability study was carried out by investigating the leakage of aceclofenac from both vesicular systems and the change in particle size when stored at (2-8ºC) for three months. The anti-inflammatory effect of the aceclofenac vesicles was assessed by the rat paw edema technique. Entrapment efficiency increased by increasing (CH) content up to an optimum level as well as by the inclusion of charge inducers and utilization of Span 60 to reach a maximum of 47.16% and 45.06% for liposomes and niosomes respectively. The particle size of the prepared vesicles was well suited for topical delivery through the skin. DSC measurements showed the interaction of aceclofenac with bilayer components. Both vesicular systems controlled the release of aceclofenac for 8 hours in which the release was affected by (CH) content, type of surfactant as well as type of charge. Aceclofenac niosomes have shown better stability compared to liposomes as manifested by drug retention levels as well as particle size change during storage. Also, aceclofenac niosomes showed superior sustained in vivo anti-inflammatory activity. The liposomal and niosomal formulations proved to be promising topical delivery systems for aceclofenac, however niosomes have proven to be more stable and was of more efficacious anti-inflammatory effect compared to liposomes.
Lipospheres were prepared using different lipid cores and phospholipid coats adopting melt and solvent techniques. Characterization was carried out through photomicroscopy, scanning electron microscopy, particle size analysis, DSC, in vitro drug release and assessment of physical stability. The anti-inflammatory effect of aceclofenac lipospheres was assessed by the rat paw edema technique and compared to the marketed product. Results revealed that the lipospheres system was able to entrap aceclofenac at very high levels (93.1%). The particle size of the prepared lipospheres was well suited for topical drug delivery. DSC revealed the molecular dispersion of aceclofenac when incorporated in lipospheres. Both entrapment efficiency and release were affected by the technique of preparation, core and coat types, core to coat ratio and drug loading. Lipospheres were very stable after three months storage at 2-8ºC manifested by low leakage rate (less than 7%) and no major changes in particle size. Finally, aceclofenac lipospheres were found to possess superior anti-inflammatory activity compared to the marketed product in both lotion and paste consistencies. Lipospheres proved to be promising topical system for the delivery of aceclofenac as they possessed the ability to entrap the drug at very high levels and high stability, and to sustain the anti-inflammatory effect of the drug.
Keywords: Aceclofenac, liposomes, niosomes, lipospheres, anti-inflammatory.