In vivo antimalarial activity of self-nanoemulsifying drug delivery systems containing ethanolic extract of Morinda lucida in combination with other Congolese plants extracts

Abstract Morinda lucida leaves are largely used by Congolese traditional healers for the treatment of uncomplicated malaria. The antimalarial activity of their ethanolic extract has been confirmed both in vitro and in vivo. However, the development of relevant formulations for potential clinical application is hampered since the active ingredients contained in this extract exhibit poor water solubility and low oral bioavailability. Hence, this work aims not only to develop self-nanoemulsifying drug delivery systems (SNEDDSs) for oral delivery of the ethanolic extract of Morinda lucida (ML) but also to evaluate its oral antimalarial activity alone and in combination with other Congolese ethanolic plant extracts (Alstonia congensis, Garcinia kola, Lantana camara, Morinda morindoides or Newbouldia laevis). Based on the solubility of these different extracts in various excipients, SNEDDS preconcentrates were prepared, and 200 mg/g of each plant extract were suspended in these formulations. The 4-day suppressive Peter's test revealed a significant parasite growth inhibiting effect for all the extract-based SNEDDS (from 55.0 to 82.4 %) at 200 mg/kg. These activities were higher than those of their corresponding ethanolic suspensions given orally at the same dose (p<0.05). The combination therapy of MLSNEDDS with other extract-based SNEDDS exhibited remarkable chemosuppression, ranging from 74.3 % to 95.8 % (for 100 + 100 mg/kg) and 86.7 % to 95.5 % (for 200 + 200 mg/kg/day). In regard to these findings, SNEDDS suspension may constitute a promising approach for oral delivery of ML alone or in combination with other antimalarial plants.

Design And In Vivo Evaluation Of Manidipine By Self-Nanoemulsifying Drug Delivery Systems

The current research is aimed at developing liquid self-nanoemulsifying drug delivery system (liquid-SNEDDS) of Manidipine for enhanced solubility and oral bioavailability. The Manidipine SNEDDS are formulated with excipients comprising of Capmul MCM (oil phase), Transcutol P (surfactant) Lutrol L 300 as co-surfactant. The prepared fifteen formulations of Manidipine SNEDDS analysed for emulsification time, percentage transmittance, particle size, in vitro drug release, and stability studies. In vivo pharmacokinetic studies of the optimized formulation were carried out in Wistar rats in comparison with control (pure drug). The morphology of Manidipine SNEDDS indicates spherical shape with uniform particle distribution. The percentage drug release from optimized formulation F14 is 98.24 ± 5.14%. The particle size F14 formulation was 22.4 nm and Z-Average 23.3 nm. The PDI and zeta potential of Manidipine SNEDDS optimized formulation (F14) were 0.313 and-5.1mV respectively. From in vivo bioavailability data the optimized formulation exhibited a significantly greater Cmax and Tmax of the SNEDDS was found to be 3.42 ± 0.46ng/ml & 2.00 ± 0.05 h respectively. AUC0-∞ infinity for formulation was significantly higher (11.25 ± 3.45 ng.h/ml) than pure drug (7.45 ± 2.24ng. h/ml). Hence a potential SNEDDS formulation of Manidipine developed with enhanced solubility and bioavailability.

Exploring the utility of the Chasing Principle: influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040 in aqueous suspension

This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol (CAR), cinnarizine (CIN) or R3040 on drug solubilization in a two-compartment lipolysis model. Correlation of drug log or solubility in SNEDDS with drug solubilization during lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:Maisine 35-1 (1:1, /) and Kolliphor RH40, with ethanol at 10% (/) were used. SNEDDS were named F65, F55 and F20 (numbers refer to the percentage of lipids) and aqueous suspensions without drug-free SNEDDS (F0) were also analyzed. While the ranking order of drug solubilization was F65=F55=F20>F0 for CAR; F65=F55>F20>F0 for CIN and F65=F55=F20>F0 for R3040 - with higher CAR solubilization than for R3040 and CIN - the ranking of of CAR, CIN and R3040 in SNEDDS was F65F20 and F65>F55>F20, respectively. Therefore, the composition of SNEDDS influenced the solubilization of CIN, but not CAR and R3040. Furthermore, high in SNEDDS did not reflect high drug solubilization. As CAR (log 3.8) showed higher solubilization than CIN (log 5.8) and R3040 (log 10.4), a correlation between drug log and drug solubilization was observed.

Development of self-nanoemulsifying tablet (SNET) for bioavailability enhancement of sertraline

The purpose of the study was to combine the advantages of self-nanoemulsifying drug delivery systems and tablets as a conventional dosage form. Self-nanoemulsifying drug delivery system (SNEDDS) was prepared to enhance the solubility and thus oral bioavailability of sertraline. Aqueous titration method was used to prepare the liquid SNEDDS; ternary phase diagrams were constructed and based on smaller droplet size (24.8 nm), minimum viscosity (153.63 cP) and polydispersity index (0.182), higher percentage transmittance (95%) and in vitro drug release (97%), an optimum system was designated. Liquid SNEDDS was transformed into free-flowing powder by solid adsorption technique followed by compression into tablets. In vitro release of sertraline from liquid and solid SNEDDS was found to be highly significant compared to plain sertraline (p<0.01). Pharmacokinetic studies after oral administration of liquid and solid SNEDDS in rats showed about 6-and 5-fold increased absorption of sertraline compared to the aqueous suspension of sertraline. These studies demonstrate that the solid SNEDDS are promising strategies for successful delivery of poorly water-soluble drug like sertraline

Intestinal lymphatic transport of matrine from two self-nanoemulsifying drug delivery systems assessed by triple single pass intestinal perfusion approach in rats / 中国药学杂志

OBJECTIVE: To investigate the differences of two matrine (MA) self-nanoemulsifying drug delivery systems (SNEDDS) in intestinal lymphatic transport. METHODS: Triple single pass intestinal perfusion model (T-SPIP) was established to study the intestinal absorption kinetics of MA in different absorption segments of rats with chylomicron flow blocking approach using colchicine as the blocker. The concentration of MA in the perfustae was measured by HPLC. RESULTS: The two SNEDDSs had regular spherical surface and narrow particle size distribution. MA showed high Peff. The phospholipid complex formulation (MPC-SN) exhibited higher intestinal lymphatic transport especially in distal ileum, and it was influenced more significantly by the chylomicron flow blocker in distal ileum compared to in proximal jejunum and mid-small intestine. CONCLUSION: SNEDDS can improve the absorption of MA by intestinal lymphatic transport. MPC-SN might be easier to be absorbed via lymphatic transport because of its high lipophilicity and small particle size.