Improved skin-permeated diclofenac-loaded lyotropic liquid crystal nanoparticles: QbD-driven industrial feasible process and assessment of skin deposition

The purpose of the present study was to optimise diclofenac diethylamine-loaded liquid crystal nanoparticles (LCNPs) using the principles of quality by design. Based on risk assessment, the effect of various formulation variables on the critical quality attributes was investigated. A three-level Box-Behnken design with 14 runs was utilised for optimisation. The LCNPs were evaluated for size, polydispersity index, zeta potential, entrapment efficiency, morphology, solid-state characterisation, and drug release. The LCNPs were found to show prolonged drug release up to 12 h as compared to the free drug which showed a 100% release in less than 3 h. The optimised formulation was further investigated for scale-up studies, incorporated into carbopol gel and characterised for rheological parameters, skin permeation, and skin accumulation. Ex-vivo skin permeation studies revealed 1.55 times more permeation as compared to the marketed formulation. The designed gel had the potential to prolong the drug release, improve the permeation of drug through the skin layers, and industrial feasibility. Continue reading here

KEYWORDS: Diclofenac diethylamine, liquid crystal nanoparticles, permeation, quality by design, skin deposition, Glyceryl monooleate (Monegyl-O100), Lutrol® F 127 *(Polaxomer 407), Carbopol® 980P **

* Lutrol® F 127 is the former trade name of Kolliphor® P 407 –  CAS-No: 9003-11-6 – INCI: Poloxamer 407
Regulatory Status: Kolliphor® P 407 meet the requirements of the current USP-NF monographs and European Pharmacopoeia family monograph Poloxamer: Ph. Eur., USP-NF: Poloxamer 407. Kolliphor ® P 407 products are also JPE certified (Japanese Pharmaceutical Excipients): Polyoxyethylene (196) Polyoxylpropylene (67) glycol. More on oleo excipients from BASF

** Carbopol® 980P  – INCI : Carbomer. Carbopol® 980 polymer is a white powder, crosslinked polyacrylic acid that is polymerized in a toxicologically-preferred cosolvent system. It is an extremely efficient rheology modifier capable of providing high viscosity and forms sparkling clear gels or hydro-alcoholic gels and creams. Its short flow, non-drip properties are ideal for applications such as clear gels, hydroalcholic gels, creams, and lotions. More on Lubrizol excipients