Formulation and Evaluation of Lidocaine Lipid Nanosystems for Dermal Delivery

Abstract

The objective of the present investigation was to formulate solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for improving the dermal delivery of a local anesthetic agent lidocaine (LID). SLN and NLC were characterized for particle size distribution, polydispersity index, entrapment efficiency, X-ray powder diffraction pattern (XRD), thermal behavior by differential scanning colorimeter (DSC) and surface morphology by transmission electron microscopy (TEM). LID-loaded SLN and NLC were formulated into hydrogels for topical application. The in vitro permeation profiles of LID SLN gel, LID NLC gel, and a marketed LID formulation (Xylocaine gel) were evaluated by using guinea pig skin. The in vivo efficacy of LID SLN gel, LID NLC gel, and a marketed LID formulation (Xylocaine gel) gel was evaluated on guinea pig using pinprick test. LID SLN showed a particle size of 78.1 nm with a polydispersity index of 0.556, whereas LID NLC showed a particle size of 72.8 nm with a polydispersity index of 0.463. The entrapment efficiency of LID in both SLN and NLC was 97% and 95.9%, respectively. The TEM studies revealed the almost spherical nature of LID SLN and NLC formulations. The XRD and DSC studies of LID SLN suggested amorphization of drug in the carrier system. The SLN formulation was stable with respect to particle size, polydispersity, and entrapment efficiency for 6 months at 40 degrees C/75% relative humidity (RH). Negligible leakage was observed for the NLC formulation when stored for 1 month at 40 degrees C/75% RH. In vitro permeation studies indicated that LID SLN gel and LID NLC gel significantly sustained the LID release compared to that of Xylocaine gel. The in vivo efficacy results supported the results of the in vitro permeation studies wherein the LID SLN gel and LID NLC gel resulted in fivefold and sixfold increase in duration of anesthesia, respectively, compared to that of Xylocaine gel.

Application of quality by design principles in the development and evaluation of semisolid drug carrier systems for the transdermal delivery of lidocaine

“…The components of the NLC formulation have similar lipophilicity as the skin, so they have good miscibility with the skin lipids, and this can cause greater penetration [37]. Our results are in good agreement with other studies, which revealed that lipid nanocarriers can improve penetration and effectiveness of encapsulated lidocaine [2,5,38,39]. The high penetration rate of LID through the epidermis predicts the fast accumulation of the drug in the dermis, which is the site of action for local anesthetics.…”

The Impact of Variables on Particle Size of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers; A Comparative Literature Review

“…The NLC formulation was evaluated for just 1 month in the above-mentioned conditions, and it was found to be stable. 49 Domperidone is a dopaminereceptor antagonist widely used in the treatment of motion sickness. Due to its poor water solubility and consequent low oral absorbability, extensive first pass metabolism which leads to poor oral bioavailability (around 15%), 50,51 therapeutic administration at low doses (10 mg) or for long-term treatment, and repetitive dosing make this drug an interesting candidate for the development of SLN and NLC.…”

Novel sulpiride-loaded solid lipid nanoparticles with enhanced intestinal permeability

“…The polydispersity index measures the width of the particle dispersion, providing information on the homogeneity of the particle size distribution of the system. The literature reports that polydispersity indices less than 0.3 are considered ideal and are referred to as indicating a narrow size distribution, 22,23 whereas polydispersity values less than 0.1 are referred to as monodispersed. 24 Therefore, according to Table 2, all the formulations had a narrow size dispersion.…”