Ionic Liquids Assisted Topical Drug Delivery for Permeation Enhancement: Formulation Strategies, Biomedical Applications, and Toxicological Perspective.

Topical drug delivery provides several benefits over other conventional routes by providing localizing therapeutic effects and also avoids the gastrointestinal tract circumventing the first-pass metabolism and enzymatic drug degradation. Being painless, the topical route also prevents the difficulties linked with the parenteral route. However, there are limitations to the current topical systems which necessitate the need for further research to find functional excipients to overcome these limitations. This review deals in depth with the ionic liquids concerning their physicochemical properties and applicability as well as their role in the arena of topical drug delivery in permeation enhancement, bioavailability enhancement of the drugs by solvation, and drug moiety modification. The review gives a detailed insight into the recent literature on ionic liquid-based topical formulations like ionic liquid-based emulsions, active pharmaceutical ingredient-ionic liquids, ionic liquid-based bacterial cellulose membranes, topical small interfering RNA (siRNA) delivery, and ionogels as a possible solutions for overcoming the challenges associated with the topical route. This review also takes into account the toxicological aspects and biomedical applications of ionic liquids.

Development and Optimization of Luliconazole Nanostructured Lipid Carriers Based Gel by Quality by Design its Skin Distribution Studies, Dermatokinetic Modeling & In-Vitro and Ex-Vivo Correlation.

AIM: The present study was aimed to improve the permeability of Luliconazole (LZ) and to localize high drug concentrations at skin layers by Quality by Design (QbD) based Nanostructured lipid carriers (NC) based gel. METHODS: Quality Target Product Profile was set, and Critical Quality attributes were identified. FT-IR and DSC studies confirmed compatibility. Risk assessment was carried out by screening the factors using 2IV7-2 fractional factorial design and optimization by Box Behnken design. Cholesterol: Cetyl Palmitate, PEG 200 and probe sonication time were identified as factors, Particle size (<200 nm), PDI (0.4), % Entrapment efficiency (% EE, >80%) and % Cumulative Drug release (% CDR, >95%) as responses. Contour plots, overlay plots and desirability, were utilized to create design space. RESULTS: The quadratic polynomial equations showed increased lipid content, PEG 200 and optimum sonication time reduced particle size, PDI, improved % EE and % CDR. The optimized formula was formulated into a gel. Ex-vivo permeation studies performed using pig ear pinna skin revealed that developed LZ NC gel exhibited greater permeation 272.98±8.57 (µg/cm2) and 32.11 ±4.7 (µg/cm2/h) flux than plain drug dispersed gel. Dermatokinetic parameters of LZ NC gel revealed that a highly significant amount of LZ was permeated, distributed and transported through the skin layers. The better linear correlations were obtained by LZ permeation through a synthetic membrane (in-vitro) and pig ear pinna skin (ex-vivo). CONCLUSION: The above findings revealed that developed LZ NC gel exhibited better permeation and localization at skin layers in treating fungal infections.

Preclinical pharmacokinetics and biodistribution studies of asenapine maleate using novel and sensitive RP-HPLC method.

AIM: Asenapine maleate (ASPM) is a newer antipsychotic drug available as a sublingual tablet in the market. EXPERIMENTAL: To investigate the pharmacokinetic and tissue distribution study of ASPM following oral administration in rats, reversed-phase HPLC method was developed and validated. RESULTS: ASPM was extracted from plasma and tissue matrix by liquid-liquid extraction technique and analyzed using mobile phase consisted of phosphate buffer pH 3.0 and acetonitrile (65:35% v/v). The method showed good linearity (10-500 ng/ml) with recovery 83-102%. In pharmacokinetics study, half-life was 32.74 ± 7.51 h due to slow elimination of drug. The biodistribution study indicated preferential distribution of ASPM to highly perfused organs. CONCLUSION: The current method can be successfully applied for estimating the drug in various biological matrices.

Development and Validation of a Stability-Indicating RP-HPLC Method by a Statistical Optimization Process for the Quantification of Asenapine Maleate in Lipidic Nanoformulations.

A stability-indicating RP-HPLC method was developed for quantification of asenapine maleate (ASPM) in lipid nanoformulations. The proposed method was used to assess intrinsic stability of ASPM by conducting force degradation study. The results indicated no considerable degradation of ASPM on subjecting it to hydrolytic, oxidative, thermal and photolytic stresses. The method was validated according to ICH Q2(R1) guidelines by employing Full factorial design using Design-Expert(®) software. ASPM was precisely and accurately quantified in nanoparticles by separating it on Hyperclone BDS C18 using 80-20% v/v mixture of potassium phosphate solution containing 0.1% v/v triethylamine and acetonitrile. The effect of flow rate, pH, acetonitrile content and column temperature was assessed on method responses. The current method was linear in the range of 0.1-20 µg/mL with limit of detection (LOD) and limit of quantification (LOQ) of 29 and 89 ng/mL, respectively. The method was precise and accurate in the determination of ASPM with peak area RSD and recovery of <1.0% and 97-101% in bulk drug solution and of <1.0% and 92-104% in nanoformulations, respectively. Analysis of variance indicated the significance (P < 0.0001) of a statistical model in validating the method with respect to change in independent chromatographic factors. The developed method was successfully employed in determining ASPM content in bulk and lipid nanoformulations.