Veerabrahma Kishan

Development and evaluation of nitrendipine loaded solid lipid nanoparticles: influence of wax and glyceride lipids on plasma pharmacokinetics.

Nitrendipine is an antihypertensive drug with poor oral bioavailability ranging from 10 to 20% due to the first pass metabolism. For improving the oral bioavailability of nitrendipine, nitrendipine loaded solid lipid nanoparticles have been developed using triglyceride (tripalmitin), monoglyceride (glyceryl monostearate) and wax (cetyl palmitate). Poloxamer 188 was used as surfactant. Hot homogenization of melted lipids and aqueous phase followed by ultrasonication at temperature above the melting point of lipid was used to prepare SLN dispersions. SLN were characterized for particle size, zeta potential, entrapment efficiency and crystallinity of lipid and drug. In vitro release studies were performed in phosphate buffer of pH 6.8 using Franz diffusion cell. Pharmacokinetics of nitrendipine loaded solid lipid nanoparticles after intraduodenal administration to conscious male Wistar rats was studied. Bioavailability of nitrendipine was increased three- to four-fold after intraduodenal administration compared to that of nitrendipine suspension. The obtained results are indicative of solid lipid nanoparticles as carriers for improving the bioavailability of lipophilic drugs such as nitrendipine by minimizing first pass metabolism.

Transbuccal Delivery of Chlorpheniramine Maleate from Mucoadhesive Buccal Patches

This article describes buccal permeation of chlorpheniramine maleate (CPM) and its transbuccal delivery using mucoadhesive buccal patches. Permeation of CPM was calculated in vitro using porcine buccal membrane and in vivo in healthy humans. Buccal formulations were developed with hydroxyethylcellulose (HEC) and evaluated for in vitro release, moisture absorption, mechanical properties, and bioadhesion, and optimized formulation was subjected for bioavailability studies in healthy human volunteers. In vitro flux of CPM was calculated to be 0.14 ± 0.03 mg.h−1.cm−2 and buccal absorption also was demonstrated in vivo in human volunteers. In vitro drug release and moisture absorbed were governed by HEC content and formulations exhibited good tensile and mucoadhesive properties. Bioavailability from optimized buccal patch was 1.46 times higher than the oral dosage form and the results showed statistically significant difference.

Brain delivery of transferrin coupled indinavir submicron lipid emulsions—Pharmacokinetics and tissue distribution

Indinavir, an antiretroviral protease inhibitor used in treatment of HIV infection has limited penetration into brain due to efflux of P-glycoprotein. The aim of this work was to develop transferrin coupled submicron lipid emulsions (SLEs) containing indinavir for delivery to brain. Stearylamine containing SLEs were prepared, characterized, tested for stability and optimized formulation (SLE-4) was developed. Transferrin was coupled to get SLE-6 by water soluble EDC method and purified by gel filtration. The coupled transferrin was quantified by modified Bradford dye assay method. The fluorescent dye (DiD oil) incorporated SLEs were used to check the brain specific delivery of SLEs. The in vivo pharmacokinetic and tissue distribution were conducted in mice. During pharmacokinetic studies, there was no significant difference in the serum levels of indinavir from SLE-1, SLE-4 and SLE-6 formulations at all time points. In tissue distribution studies the therapeutic availability (TA) of indinavir in brain from SLE-6 was 4.69, 3.1 and 1.7 times higher than drug solution, SLE-1 and SLE-4 respectively whereas, the TA of indinavir from SLE-4 was 2.76 and 1.82 times the drug solution and SLE-1. The brain to serum ratios with SLE-6 were above one indicates the brain specific delivery. The brain delivery of indinavir was improved with transferrin ligand attachment to SLEs by receptor mediated transcytosis.

Folate-PEG-decorated docetaxel lipid nanoemulsion for improved antitumor activity.

AIM To develop a folate-based docetaxel lipid nanoemulsion (FLNE) for tumor-targeted treatment. MATERIALS & METHODS The docetaxel LNEs were prepared and characterized. In vitro cytotoxic and cell uptake studies were performed. The tissue distribution and targeting of drug were studied by fluorescence imaging and tumor regression in mice. RESULTS The IC50 values of FLNE on cancer cells were significant. The cell uptake studies showed an increase in fluorescence with time. Imaging studies found that FLNE was superior in tumor targeting by 4.81- and 2.08-fold over controls. The tumor regression proved the superiority of FLNEs. CONCLUSION The folate strategy was superior over PEGylation, albumin and transferrin strategies. The study demonstrated great potential of FLNE as a prospective targeted delivery system.

Albumin anchored docetaxel lipid nanoemulsion for improved targeting efficiency - preparation, characterization, cytotoxic, antitumor and in vivo imaging studies.

Abstract The aim was to develop albumin anchored docetaxel lipid nanoemulsion (ALNE) for improving tumor targeted delivery. The O/W lipid nanoemulsion, LNEs were prepared by homogenization and ultrasonication processes. The size of globules and zeta potential were measured by Malvern Zetasizer. Albumin was coupled to stearylamine containing lipid nanoemulsion (SALNE) globules using water soluble EDC reaction. The drug content and entrapment efficiencies for the LNEs were determined by the high-performance liquid chromatography. The in vitro cytotoxic studies of the delivery systems were performed on MCF-7 and Hela cells. The IC 50 values of ALNE on both the cell lines were statistically significant. The in vivo antitumor activity was tested on solid tumors induced in C57BL/6 mice. This study revealed that the percentage tumor inhibition for the groups treated with DLNE, SALNE and ALNE when compared with untreated control was found to be 55.62 ± 5.41%, 54.27 ± 4.85% and 80.01 ± 2.74%, respectively. Furthermore, in vivo distribution studies were carried out in breast cancer MDA-MB231 xenografted Balb/c mice. The LNEs were loaded with fluorescent DiD oil and the distribution in different organs after 6 h was tracked using Caliper life sciences in vivo imaging system. The studies revealed that ALNE was superior in tumor targeting activity when compared with DLNE and SALNE by 3.04 and 2.26 folds, respectively. The average radiance values of ALNE on the tumor tissue were statistically significant when compared with DLNE, SALNE at p < 0.01. In addition, this strategy can become a platform technology for other lipophilic drugs to target tumors.

Improvement of anti-hyperlipidemic activity and oral bioavailability of Fluvastatin via solid self-microemulsifying systems and comparative with liquisolid formulation

BACKGROUND FR&D scientists continuously try to increase the in vivo performance of low soluble and bioavailable drugs. Solid SMEDDS and liquisolid formulations are relatively simple to develop and fall within the novel drug delivery approaches. Here, a comparison is made to know relative superiority. OBJECTIVE The study aimed to conduct comparative pharmacokinetic (PK) and pharmacodynamic (PD) studies of developed Fluvastatin (FLU) solid SMEDDS (SSMED) and liquisolid formulation (LS) for their relative in vivo efficacy. METHOD FLU liquid SMEDDS were optimized by central composite design (CCD). Components, oil, surfactant and co-surfactant were selected as variables; particle size, self-emulsifying time and % drug release in 15min were selected as responses. L-SMEDDS with positive charge inducer were adsorbed on to porous carriers and characterized. Liquisolid formulations were prepared with Avicel PH-102 and Neusilin US2 as carriers. RESULTS Optimized L-SMEDDS contained 24.92 mg of oil, 45.18 mg of surfactant and 34.28 mg of cosurfactant. SSMEDs containing Syloid XDP (SSMED-XDP) as carrier was selected based on flow properties and liquid retention potential. The average particle size of SSMED-XDP was 154.30±1.10 nm, PDI was 0.311±0.03 and ZP was +19.57±1.34 mV after dilution. The drug release from SSMEDXDP and LS formulations was higher than FLU powder. The bioavailability of SSMEDs was increased by 3.00 fold and that of LS by 1.49 fold more than FLU-suspension. SSMEDs showed 12 h, while LS and suspension showed only 6 h lipid-lowering effect. CONCLUSION The development of solid SMEDDS resulted in superior performance in both PK and PD effects over the LS formulation.