Category: Formulation and Quality
Purpose: Oxicams, BCS Class II drugs belonging to the class of NSAIDS (non-steroidal anti-inflammatory drugs) are potent hydrophobic compounds indicated in conditions of rheumatoid arthritis, ankylosing spondylitis and osteoarthritis in which rapid onset of drug action is desired to reduce inflammation and pain. However, many adverse effects (such as Nausea, upset stomach, diarrhea, dizziness etc.) are reported when they are administrated orally. The objective of this study is to develop deformable liposomes of meloxicam (model drug) to enhance the solubility and permeation for topical drug delivery across the stratum corneum for local (dermal), or systemic (transdermal) effects, to significantly reduce inflammation and pain and thereby greatly reduce the side effects.
Methods: Meloxicam loaded deformable liposomes were prepared by the thin film hydration method followed by sonication. Chemical analysis was performed by using an HPLC method for the quantitation of meloxicam to determine its entrapment efficiency and amount found in human skin samples following permeation studies. Physical characterization of particle size and zeta potential were determined using a Malvern Zetasizer DLS (Dynamic Light Scattering). Morphology, thermodynamic and visualization tests, such as transmission electron microscopy (TEM), differential scanning calorimetry (DSC), confocal microscopy (CLSM), were utilized to characterize the vesicles and understand the mechanism of penetration of these deformable liposomes. After the characterization, an in vitro skin permeation study was performed using Franz diffusion cells with human cadaver skin samples.
Results: As summarized in Table 1, the deformable liposomes of meloxicam (MX) were composed of phospholipid (PL), cetylpyridinium chloride (CPC), cholesterol (Chol) and/or permeation enhancer menthol (Men), anti-oxidant poplyphenol-1 (PP-1) and polyphenol-2 (PP-2). Formulations 1 to 4 were prepared based on the studies conducted by Duangjit1. Formulation 5 was prepared to study the effect of menthol in the liposome formulation. Formulations 6 and 7 were made using two different polyphenol compounds, which acted as both anti-oxidants and additional anti-inflammatory drugs.
The results indicated that these deformable liposomes of meloxicam provided substantial enhancement of meloxicam solubility compared to conventional liposomes (controls: F1 and F2), demonstrating much higher entrapment rates (70-100% vs 20%) and smaller, homogeneous particles, as shown in Table 1. Notably, the deformable liposomes containing polyphenols showed higher entrapment rate compared to transfersomes and menthosomes transdermal technology platforms.
Preliminary skin permeation study has been conducted using Franz Diffusion Cells on human cadaver skins. The obtained results also revealed meloxicam loaded deformable liposomes improved permeability, as demonstrated in Figures 1 and 2.
Specifically, permeation results of Formulation 7 (containing PP-1) showed the highest amount of meloxicam resided in the skin, while that of Formulation 6 displayed the highest amount of meloxicam penetrated through the skin and detected in receptor compartments.
Conclusion: Different compositions of deformable liposomes have been developed with high drug entrapment rate, homogeneous particle size and improved solubility and permeability. The dermal and transdermal delivery using deformable liposomes can be a promising alternative to conventional oral delivery of NSAIDS with enhanced local and systemic onset of action and reduced side effects.
Reference: Duangjit S, et al. Comparative study of novel ultradeformable liposomes: menthosomes, transfersomes and liposomes for enhancing skin permeation of meloxicam. Biol Pharm Bull. 2014;37(2):239-47.
Zhang Zhang– Piscataway, New Jersey
Zhang Zhang– Piscataway, New Jersey
Bozena Michniak-Kohn– Professor of Pharmaceutics, Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey
Julia Zhang– Ph.D Student, Rutgers University, Piscataway, NJ