Liquid Self-nanoemulsifying Drug Delivery System Research Articles

Analysis of 3D Prints by X-ray Computed Microtomography and\xa0Terahertz Pulsed Imaging

PurposeA 3D printer was used to realise compartmental dosage forms containing multiple active pharmaceutical ingredient (API) formulations. This work demonstrates the microstructural characterisation of 3D printed solid dosage forms using X-ray computed microtomography (XμCT) and terahertz pulsed imaging (TPI).MethodsPrinting was performed with either polyvinyl alcohol (PVA) or polylactic acid (PLA). The structures were examined by XμCT and TPI. Liquid self-nanoemulsifying drug delivery system (SNEDDS) formulations containing saquinavir and halofantrine were incorporated into the 3D printed compartmentalised structures and in vitro drug release determined.ResultsA clear difference in terms of pore structure between PVA and PLA prints was observed by extracting the porosity (5.5% for PVA and 0.2% for PLA prints), pore length and pore volume from the XμCT data. The print resolution and accuracy was characterised by XμCT and TPI on the basis of the computer-aided design (CAD) models of the dosage form (compartmentalised PVA structures were 7.5 ± 0.75% larger than designed; n = 3).ConclusionsThe 3D printer can reproduce specific structures very accurately, whereas the 3D prints can deviate from the designed model. The microstructural information extracted by XμCT and TPI will assist to gain a better understanding about the performance of 3D printed dosage forms.

Nanoemulsifying drug delivery system to improve the bioavailability of piroxicam

Objective: The aim of this study is to develop and characterize self-nanoemulsifying drug delivery system (SNEDDS) of piroxicam in liquid and solid forms to improve its dissolution, absorption and therapeutic efficacy.Materials and methods: The generation of liquid SNEDDS (L-SNEDDS) was composed of soybean or coconut oil/Tween 80/Transcutol HP (12/80/8%w/w) and it was selected as the optimized formulation based on the solubility study and pseudo-ternary phase diagram. Optimized L-SNEDDS and liquid supersaturatable SNEDDS (L-sSNEDDS) preparations were then adsorbed onto adsorbents and formulated as directly compressed tablets.Results and discussion: The improved drug dissolution rate in the solid supersaturatable preparation (S-sSNEDDS) may be due to the formation of a nanoemulsion and the presence of drug in an amorphous state with hydrogen bond interaction between the drug and SNEDDS components. In vivo pharmacokinetic studies on eight healthy human volunteers showed a significant improvement in the oral bioavailability of piroxicam from S-sSNEDDS (F12) compared with both the pure drug (PP) and its commercial product (Feldene®) (commercial dosage form (CD)). The relative bioavailability of S-sSNEDDS (F12) relative to PP or CD was about 151.01 and 98.96%, respectively.Conclusion: The obtained results ratify that S-sSNEDDS is a promising drug delivery system to enhance the oral bioavailability of piroxicam.

Development and Optimization of Solid Self Nanoemulsifying Drug Delivery (S-SNEDDS) Using D-Optimal Design for Improvement of Oral Bioavailability of Amiodarone Hydrochloride

The solid-self nanoemulsifying drug delivery system (S-SNEDDS) of Amiodarone hydrochloride (AH) was prepared and evaluated. AH exhibits poor aqueous solubility (0.3-0.5 mg/ml) and therefore variable oral bioavailability. Capmul MCM, Cremophor RH-40 and Propylene glycol were identified as oil, surfactant and co-surfactant for preparing L-SNEDDS. D-optimal design was used to optimize the amount of components in liquid self nanoemulsifying drug delivery system (L-SNEDDS). Optimized AH-L-SNEDDS having 15.8 nm globule size and 99.5 %transmittance was then adsorbed on Neusilin US2 to form solid self nanoemulsifying drug delivery system (AH-SSNEDDS). AH loaded L-SNEDDS and S-SNEDDS were characterized for various physicochemical properties and solid state properties. In vitro dissolution, ex vivo drug release study and In vivo study were performed for pure AH, AH-LSNEDDS and AH-S-SNEDDS. Both AH loaded L-SNEDDS and S-SNEDDS showed more than 95% drug release in 20 min during drug release studies. In vivo study revealed that release of AH from S-SNEDDS was 2.26 times and LSNEDDS was 1.83 times higher than that from suspension when given to rabbits (p < 0.01). The optimized S-SNEDDS was found to be stable and its shelf life was found to be 2.2 years. S-SNEDDS could serve as a potential drug delivery system for AH.

Effect of Lipophilicity of Drugs on Dissolution Profiles of Self-Nanoemulsifying Drug Delivery System

The low solubility of poorly water-soluble drug is a major problem of oral drug adsorption. The self-emulsifying system can be applied to eliminate the drug dissolution step and improve the drug absorption. In this research, liquid self-nanoemulsifying drug delivery system (SNEDDS) composing of polyethoxylated castor oil, caprylic/capric glyceride and diethylene glycol monoethyl ether was developed. The drugs with similar structure but different lipophilicity (log P), nifedipine (NDP), felodipine (FDP) and manidipine (MDP), were investigated. Size and size distribution of emulsion after dilution in acid medium and in vitro drug dissolution were determined. The results showed that the size of emulsions obtained from dilution of SNEDDS in acidic medium ranged from 100-150 nm. Drug dissolution from SNEDDS was different depending on lipophilicity of drug, i.e., 98.6, 74.3 and 52.5% for NDP (log P 2.50), FDP (log P 4.46) and MDP (log P 5.46), respectively. The results suggested that the difference in lipophilicity may influence the drug dissolution from SNEDDS.

Development and optimization of solid self-nanoemulsifying drug delivery system (S-SNEDDS) using Scheffe's design for improvement of oral bioavailability of nelfinavir mesylate.

The present research was aimed at development and evaluation of self-nanoemulsifying drug delivery system (SNEDDS) for improving bioavailability of nelfinavir mesylate (NFV), a protease inhibitor exhibiting pH dependent solubility and variable oral bioavailability. Maisine 35-1, Cremophor RH-40, and Labrasol were identified as oil, surfactant, and co-surfactant that had best solubility for NFV. Scheffe's mixture design was used to optimize the amount of components in liquid self-nanoemulsifying drug delivery system (L-SNEDDS) by taking their amounts as independent variable, whereas globule size, drug loading, and percent transmittance were taken as dependent variable. Optimized NFV-L-SNEDDS was then adsorbed on Neusilin US2 to form solid self-nanoemulsifying drug delivery system (S-SNEDDS). NFV loaded L-SNEDDS and S-SNEDDS were characterized for various physicochemical properties, and solid-state properties were determined through differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy studies. In vitro dissolution using simulated gastric fluid and simulated intestinal fluid, ex vivo drug release study, and in vivo study were performed for pure NFV and NFV-S-SNEDDS. NFV-S-SNEDDS showed more than 90% drug release in 20min during drug release studies irrespective of pH of the dissolution medium. In vivo study revealed significant difference between release of NFV from suspension and NFV-L-SNEDDS and NFV-S-SNEDDS when given to rabbits (p < 0.001). NFV-L-SNEDDS and NFV-S-SNEDDS were subjected to stability study as per ICH guidelines, and NFV-S-SNEDDS was found to be stable during the period of study. S-SNEDDS could serve as a potential drug delivery system for NFV.

Self-Nanoemulsifying Powder of Isotretinoin: Preparation and Characterization

In the present investigation an attempt was made to enhance the solubility and dissolution of poorly soluble drug, isotretinoin, by formulating self-nanoemulsifying drug delivery system (SNEDDS). Liquid SNEDDSs were prepared using Transcutol P as oil, Tween 80 as surfactant, and PEG 400 as cosurfactant. Pseudoternary phase diagrams were constructed to identify the efficient self-nanoemulsification region. The formulation with 40% oil (Transcutol P) and 60% surfactant: cosurfactant (Tween 80: PEG 400) ratio of 1 : 1 was optimized based on evaluation parameters for droplet size analysis, self-emulsification capacity, zeta potential, and in vitro drug release performance. The optimized system contains mean droplet size of 36.60 nm and zeta potential (ζ) −26.73 mV. The optimized formulation A1 was adsorbed onto Fujicalin to produce solid SNEDDS, which exhibited good flow properties and preserved the self-emulsification properties of liquid SNEDDS. The differential scanning calorimetry, FT-IR studies of solid SNEDDS revealed transformation of isotretinoin into molecularly dissolved state in the liquid SNEDDS. In vitro dissolution profiles showed that dissolution rate of ISN from solid SNEDDS was significantly greater as compared to pure drug.

Physicochemical characterization and in vivo evaluation of solid self-nanoemulsifying drug delivery system for oral administration of docetaxel

To formulate a self-nanoemulsifying drug delivery system (SNEDDS) for the oral administration of docetaxel as an alternative to commercial docetaxel-loaded injectable products, it was prepared by spray-drying an aqueous solution containing liquid SNEDDS and colloidal silica. Its physicochemical properties and oral bioavailability were investigated compared to a clear docetaxel solution administered intravenously or orally to rats. In the docetaxel-loaded solid SNEDDS prepared with colloidal silica, the liquid SNEDDS composed of Capryol 90, Cremophore EL and Transcutol HP (45/35/20, volume ratio) was absorbed inside the pores of carriers, and docetaxel was present in a changed amorphous state. The solid SNEDDS with 3.3% (w/v) docetaxel produced nanoemulsions, and showed about 12.5% absolute bioavailability in rats. Thus, this solid SNEDDS may be a potential candidate for oral pharmaceutical product with improved oral bioavailability of docetaxel.