Rengarajan Baskaran

Solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine for enhanced bioavailability of highly lipophilic bioactive carotenoid lutein

The objectives of this study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine (PC), an endogenous phospholipid with excellent in vivo solubilization capacity, as oil phase for the delivery of bioactive carotenoid lutein, by spray drying the SNEDDS (liquid system) containing PC using colloidal silica (Aerosil® 200 VV Pharma) as the inert solid carrier, and to evaluate the enhanced bioavailability (BA) of lutein from S-SNEDDS. The droplet size analyses revealed droplet size of less than 100 nm. The solid state characterization of S-SNEDDS by SEM, DSC, and XRPD revealed the absence of crystalline lutein in the S-SNEDDS. The bioavailability study performed in rabbits resulted in enhanced values of C(max) and AUC for S-SNEDDS. The enhancement of C(max) for S-SNEDDS was about 21-folds and 8-folds compared with lutein powder (LP) and commercial product (CP), respectively. The relative BA of S-SNEDDS compared with CP or LP was 2.74-folds or 11.79-folds, respectively. These results demonstrated excellent ability of S-SNEDDS containing PC as oil phase to enhance the BA of lutein in rabbits. Thus, S-SNEDDS containing PC as oil phase could be a useful lipid drug delivery system for enhancing the BA of lutein in vivo.

Novel self-nanoemulsifying drug delivery system for enhanced solubility and dissolution of lutein

Self-nanoemulsifying drug delivery system (SNEDDS) containing oil (Phosal 53 MCT), surfactant (Labrasol), and cosurfactant (Transcutol-HP or Lutrol-E400) was prepared to enhance solubility and dissolution of lutein. Ternary phase diagram of the SNEDDS was constructed to identify the self-emulsifying regions following which the percentage of oil, surfactant, and cosurfactant in the SNEDDS were optimized in terms of emulsification time and mean emulsion droplet size. The optimized SNEDDS consists of 25% oil, 60% surfactant, and 15% cosurfactant. When measured using USP XXIII dissolution apparatus II, the emulsification time of the SNEDDS prepared with Transcutol-HP as cosurfactant was less than 20 sec, and it was 20–30 sec in the SNEDDS prepared with Lutrol-E400. Mean emulsion droplet size was slightly smaller when Transcutol-HP was used as cosurfactant (80 ± 6 nm), compared to when Lutrol- E400 was used (93 ± 6 nm). Dissolution of lutein from the solid SNEDDS (physical mixture of the optimized SNEDDS and Aerosil 200) took place immediately (less than 5 min) in distilled water, and, once dissolved, no precipitation or aggregation of the drug were observed. In contrast, no drug was released from lutein powder or from the commercial product (Eyelac®) until 3 h of the study duration.

Physicochemical characterization and skin permeation of liposome formulations containing clindamycin phosphate

This study was undertaken to evaluate the physicochemical properties and skin permeation of liposome formulations containing clindamycin phosphate (CP), especially when charge was imparted to the liposome. Five different liposome formulations were prepared using Phospholipon 85G (PL) and cholesterol (CH) by conventional lipid film hydration technique. Molar ratio of CH to PL was varied in the range of 0.16–1.0. Charged liposomes were prepared in the same way with addition of 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) and 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA) as charge carrier lipid for cationic or anionic charge of the liposome, respectively. Fresh full-thickness mice skin was taken and used for skin permeation study using Keshary-Chien diffusion cell with 1.77 cm2 diffusion area at 37°C. All liposome formulations prepared showed homogeneous size distribution with mean particle size of about 1 μm or less. Among the five liposome formulations prepared, formulation with the molar ratio of 0.5 showed the best result in the physicochemical properties such as polydispersity index, entrapment efficiency, size evolution, and ability of the liposome to retain CP as of entrapped in the vesicles. Charge-impartation of the formulation with cationic charge carrier lipid resulted in additional benefit in terms of inhibition of size evolution, the ability of the liposome to retain CP in the vesicles, and skin permeation. Steady state flux of the drug through the mice skin in the cationic liposome vesicles was 0.75 ± 0.01 μg/cm2h while that in the control (dissolved into mixed alcohol solution) was 0.17 μg/cm2h. One half molar ratio of CH to PL was optimal in terms of physicochemical properties of the liposome formulation containing CP, and incorporation of cationic charge carrier lipid appeared to provide additional benefits for the stability of the liposome formulation and skin permeation of the drug.

Self-nanoemulsifying drug delivery system of lutein: physicochemical properties and effect on bioavailability of warfarin.

Objective of present study was to prepare and characterize self-nanoemulsifying drug delivery system (SNEDDS) of lutein and to evaluate its effect on bioavailability of warfarin. The SNEDDS was prepared using an oil, a surfactant, and co-surfactants with optimal composition based on pseudo-ternary phase diagram. Effect of the SNEDDS on the bioavailability of warfarin was performed using Sprague Dawley rats. Lutein was successfully formulated as SNEDDS for immediate self-emulsification and dissolution by using combination of Peceol as oil, Labrasol as surfactant, and Transcutol-HP or Lutrol-E400 as co-surfactant. Almost complete dissolution was achieved after 15 min while lutein was not detectable from the lutein powder or intra-capsule content of a commercial formulation. SNEDDS formulation of lutein affected bioavailability of warfarin, showing about 10% increase in Cmax and AUC of the drug in rats while lutein as non-SNEDDS did not alter these parameters. Although exact mechanism is not yet elucidated, it appears that surfactant and co-surfactant used for SNEDDS formulation caused disturbance in the anatomy of small intestinal microvilli, leading to permeability change of the mucosal membrane. Based on this finding, it is suggested that drugs with narrow therapeutic range such as warfarin be administered with caution to avoid undesirable drug interaction due to large amount of surfactants contained in SNEDDS.

Preparation, Characterization, and Release Study of Tacrolimus-Loaded Liquid Crystalline Nanoparticles

The use of liquid crystalline nanoparticles is a novel approach in the field of controlled drug delivery. Tacrolimus, being a highly lipophilic drug, is easily incorporated in the hydrophobic core of these nanoparticles, which are prepared using monoolein, distilled water, and varying ratios of poloxamer 407. Characterization, including transmission electron microscopy (TEM) images, particle size, and entrapment efficiency analysis suggested the formation of cubosomes with a particle size ranging from 140 to 155 nm and entrapment level of tacrolimus as high as 99% or above. In vitro release studies, revealed a sustained release of tacrolimus for 2 weeks, with a high stability profile of nanoparticles and incorporated drug during the storage period. Therefore, it suggests the possible use of tacrolimus-loaded formulation for intradermal delivery can be useful in the treatment of locally affecting autoimmune skin disease such as psoriasis.

In vitro release and skin permeation of tacrolimus from monoolein-based liquid crystalline nanoparticles

The objective of the present study was to determine the effect of different ratios of monoolein and oleic acid on in vitro release and skin permeation of tacrolimus from monoolein-based liquid crystalline nanoparticles. The nanoparticles were prepared by sonicating a mixture of melted monoolein, poloxamer 407, oleic acid and tacrolimus to which distilled water was added. Formation of cubosomes and hexosomes was confirmed by transmission electron microscopy and optical microscopy, and average particle size of the formulations was about 150-200 nm. The encapsulation efficiency for tacrolimus in all the formulations was > 99 %. In vitro release of the drug was proportionally reduced by the amount of monoolein used. Addition of oleic acid further reduced the tacrolimus release. The skin permeation was also in agreement with the in vitro release. This study provides a strategy to control the release and skin permeation of tacrolimus from nanoparticles, thus expanding the area of tacrolimus usage.

Effect of saturated fatty acids on tacrolimus-loaded liquid crystalline nanoparticles

Liquid crystalline nanoparticles are unique structures that can be used in the delivery of a wide range of pharmaceutical actives. Herein, we studied the effect of saturated fatty acids on tacrolimus-loaded monoolein liquid crystalline nanoparticles stabilized with poloxamer 407. Characterization of nanoparticles included optical and transmission electron microscopy, particle size, and entrapment efficiency analysis. Microscope data suggested the formation of cubosomes for monoolein dispersions, and of hexosomes for monoolein-fatty acid systems. Entrapment efficiency of tacrolimus was as high as 99 % or above. In vitro release study revealed that amount of monoolein and carbon chain lengths of the fatty acid were the factors that affected drug release from the liquid crystalline nanoparticles. Notably, monoolein-fatty acid systems prepared with short chain length, such as lauric and myristic acid, showed markedly sustained release profile of the drug. Hence, appropriate selection of fatty acid can be exploited to achieve desired release profile from monooloein liquid crystalline nanoparticles.

The effect of coenzyme Q10 on the pharmacokinetic parameters of theophylline

Interaction of a drug with other drugs and dietary supplements is becoming an emerging issue for patients and health insurance authorities due to awareness of adverse drug event. In this study, we examined the effects of coenzyme Q10 (CoQ10), one of the most popular dietary supplements, on the pharmacokinetic parameters of theophylline in rats. The pharmacokinetic parameters of theophylline changed significantly when the drug was administered after five consecutive days of pretreatment with CoQ10. Time to reach maximum plasma concentration of theophylline delayed when the drug was administered after the pretreatment with CoQ10. Maximum plasma concentration and area under the curve of theophylline were about two-fold increased and other pharmacokinetic parameters such as half-life and volume of distribution were also changed significantly. Therefore, although CoQ10 is generally considered a safe dietary supplement, it appears that patients on theophylline therapy should use caution when they take CoQ10.