Preparation and characterization of an oridonin nanosuspension for solubility and dissolution velocity enhancement

This study describes the preparation of an oridonin (ORI) nanosuspension by high-pressure homogenization (HPH). The aim was to obtain a stable nanosuspension with an increased drug saturation solubility and dissolution velocity. The homogenization procedure was optimized in regard to particle size and long-term stability. The characteristics of the oridonin nanosuspension, such as particle size, size distribution, shape, and zeta potential, were evaluated following the water removal. The solubility and dissolution experiments were performed to verify the obvious improvement of the dissolution behavior compared with commercial ORI. Finally, crystalline state evaluation before and following the formulation was performed through differential scanning calorimetry (DSC) and powder X-ray (PXRD).     

Proof-of-concept preparation and characterization of dual-drug amorphous nanoparticle complex as fixed-dose combination of poorly soluble drugs

Objectives: To carry out a proof-of-concept study on the development of dual-drug amorphous nanoparticle complex (nanoplex in short) as a potential formulation platform for fixed-dose combination (FDC) of poorly-soluble drugs.

Significance: FDC has been proven effective in improving patient compliance for treatment that requires complex multidrug regimen. Currently, there is growing interest to develop FDC of poorly-soluble drugs due to the increased number of drugs exhibiting poor solubility thus low bioavailability.

Methods: The dual-drug nanoplex was prepared by electrostatically-driven co-complexation of drug molecules with oppositely charged dextran sulfate, using ciprofloxacin (CIP) and itraconazole (ITZ) as the model poorly-soluble drugs.

Results: We first verified that the co-complexation products were dual-drug CIP-ITZ nanoplex, and not binary mixtures of the single-drug CIP and ITZ nanoplexes, by demonstrating their distinct thermal behaviors and dissolution characteristics. Depending on the preparation condition, the dual-drug nanoplex exhibited size and zeta potential of 160–410?nm and ?35–50?mV, respectively. The individual drug payloads were readily manipulated by varying the CIP/ITZ mass ratio in the feed, resulting in CIP and ITZ payloads in the range of 60-30% and 15-45%, respectively. The CIP-ITZ nanoplex, however, exhibited diminished CIP supersaturation generation, thus lower CIP solubility enhancement, compared to the single-drug CIP nanoplex. The CIP-ITZ nanoplex, nonetheless, remained capable of generating high ITZ supersaturation level.

Conclusion: Dual-drug nanoplex was successfully prepared with a high degree of control over its physical characteristics. Nevertheless, whether dual-drug nanoplex always exhibits diminished solubility enhancement compared to its single-drug counterparts needs to be investigated using different poorly-soluble drugs.     

Enhancing oral bioavailability of poorly soluble drugs with mesoporous silica based systems: opportunities and challenges

Porous silica-based drug delivery systems have shown considerable promise for improving the oral delivery of poorly water-soluble drugs. More specifically, micro- and meso-porous silica carriers have high surface areas with associated ability to physically adsorb high-drug loads in a molecular or amorphous form; this allows molecular state drug release in aqueous gastrointestinal environments, potential for supersaturation, and hence facilitates enhanced absorption and increased bioavailability. This review focuses primarily on the ability of porous silica materials to modulate in vitro drug release and enhance in vivo biopharmaceutical performance. The key considerations identified and addressed are the physicochemical properties of the porous silica materials (e.g. the particle and pore size, shape, and surface chemistry), drug specific properties (e.g. pKa, solubility, and nature of interactions with the silica carrier), potential for both immediate and controlled release, drug release mechanisms, potential for surface functionalization and inclusion of precipitation inhibitors, and importance of utilizing relevant and effective in vitro dissolution methods with discriminating dissolution media that provides guidance for in vivo outcomes (i.e. IVIVC).     

Factors influencing the erosion rate and the drug release kinetics from organogels designed as matrices for oral controlled release of a hydrophobic drug

Abstract

This article proposes solid-like systems from sunflower oil structured with a fibrillar network built by the assembly of 12-hydroxystearic acid (12-HSA), a gelator molecule for an oil phase. The resulting organogels were studied as oral controlled release formulations for a lipophilic drug, Efavirenz (EFV), dissolved in the oil. The effects of the gelator concentration on the thermal properties of the organogels were studied by Differential Scanning Calorimetry (DSC) and showed that drug incorporation did not change the sol–gel–sol transitions. The erosion and drug release kinetics from organogels under conventional (filling gelatin capsules) or multiparticulate (beads obtained by prilling) dosage forms were measured in simulated gastric and intestinal fluids. EFV release profiles were analyzed using model-dependent (curve-fitting) and independent approaches (Dissolution Efficiency DE). Korsmeyer–Peppas was the best fitting release kinetic model based on the goodness of fit, revealing a release mechanism from organogels loaded with EFV different from the simple drug diffusion release mechanism obtained from oily formulations. From organogels, EFV probably diffuses through an outer gel layer that erodes releasing oil droplets containing dissolved EFV into the aqueous medium.     

Enhanced structural and optical properties of ZnO nanopowder with tailored visible luminescence as a function of sodium hydroxide to zinc sulfate mass ratio

ZnO nanopowders of tailored particle sizes were synthesized using a simple wet chemical method, by controlling the mass ratio of the precursors. The physical properties were investigated as a function of OH^?/Zn²⁺ mass ratio (x). The structural properties of the synthesized nanoparticles (NPs) are studied using X-ray diffraction (XRD). XRD patterns show pure wurtzite structure. Microstructural parameters dependence on x ratio was studied based on Williamson-Hall model. We notice an increase in crystallite size (17–24?nm) and a decrease in strain values when the x ratio increases (0.5–1.4). The best crystallinity corresponds to the higher mass ratio. Indeed, for x?=?1.4 we obtain the largest crystallite size, the lowest strain and stacking faults. The TEM images support the XRD results. Raman spectra confirm the purity of the synthesized ZnO powder. Furthermore, the optical properties were examined by UV–vis and Photoluminescence as a function of precursor’s ratio. Absorption data show a band gap red-shift of the ZnO-NPs with increase in particle’s size. Moreover, we found that the ZnO-NPs luminescence in the visible range can be engineered by changes of x ratio. This constitutes an advantage for the use of ZnO-NPs in different wavelength areas in optoelectronic applications covering UV-Blue-Green domain for the LED design, sensors…     

Design of experiments as a strategy for modulating the colloidal stability,physico-chemical properties and drug-delivery potential of small mesoporous silica nanoparticles

The synthesis of highly stable small mesoporous silica nanoparticles (SMSN) in colloid dispersions is still challenging for biomedical applications. This study is focus on the successfully synthesis and formulation of porous, highly dispersed and colloidal stable SMSN via the soft–templating method. This study reports how the differences in synthesis variables, namely, temperature, amount of triethylamine (TEA) and/or cetyltrimethylammonium bromide (CTAB) influence the morphology and textural properties of SMSN. The analysis of the particle size, surface area, pore size, pore volume, zeta potential, and colloidal stability (represent by absorbance decreasing rate) show that temperature is the most influential factor governing the preparation of SMSN. The optimal conditions found for the synthesis of these nanoparticles were 50 °C, using a molar ratio between TEA and CTAB (3.5971: 1). Therefore, our study shows interesting insights on the effect of each variable to control the morphology and properties of small MSN for the design of this kind of nanoparticulated systems, therefore, giving valuable data to be considered for the future construction of tailor-made effective drug carrier materials.     

Granulated colloidal silicon dioxide-based self-microemulsifying tablets,as a versatile approach in enhancement of solubility and therapeutic potential of anti-diabetic agent: formulation design and in vitro/in vivo evaluation

The current research work was executed with an aim to explore and promote the potential of self-microemusifying drug delivery systems (SMEDDS) in the form of tablets, in order to enhance solubility and oral bioavailability of poorly aqueous soluble drug Repaglinide (RPG). RPG-loaded liquid SMEDDS were developed consisting Labrafil M 1944CS, Kolliphor EL and Propylene glycol, which were then characterized on various parameters. After characterization and optimization, liquid SMEDDS were converted into solid form by adsorbing on Aeroperl® 300 pharma and polyplasdone^TM XL. Further, selection of suitable excipients was done and mixed with prepared solidified SMEDDS powder followed by the preparation of self-microemulsifying tablets (SMET’s) wet granulation–compression method. SMET’s were subjected to differential scanning calorimetry (DSC) and particle X-ray diffraction (RXRD) studies, results of which indicated transformation of crystalline structure of RPG because of dispersion of RPG at molecular level in liquid SMEDDS. This was further assured by micrographs obtained from scanning electron microscope. SMET’s shown more than 85% (30?min) of in vitro drug release in contrast to conventional marketed tablets (13.2%) and pure RPG drug (3.2%). Results of in vivo studies furnished that SMET’s had shown marked decrease in the blood glucose level and prolonged duration of action (up to 8?h) in comparison with conventional marketed tablets and pure RPG drug. In conclusion, SMET’s serves as a promising tool for successful oral delivery of poorly aqueous soluble drug(s) such as RPG.     

Lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan as a new strategy for oral delivery of insulin: in vitro,ex vivo and in vivo characterizations

Objective: The purpose of this research was the development, in vitro, ex vivo and in vivo characterization of lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of chitosan.

Methods: Insulin nanoparticles were prepared from methylated N-(4-N,N-dimethylaminobenzyl), methylated N-(4 pyridinyl) and methylated N-(benzyl). Insulin nanoparticles containing non-modified chitosan and also trimethyl chiotsan (TMC) were also prepared as control. The effects of the freeze-drying process on physico-chemical properties of nanoparticles were investigated. The release of insulin from the nanoparticles was studied in vitro. The mechanism of the release of insulin from different types of nanoparticles was determined using curve fitting. The secondary structure of the insulin released from the nanoparticles was analyzed using circular dichroism and the cell cytotoxicity of nanoparticles on a Caco-2 cell line was determined. Ex vivo studies were performed on excised rat jejunum using Frantz diffusion cells. In vivo studies were performed on diabetic male Wistar rats and blood glucose level and insulin serum concentration were determined.

Results: Optimized nanoparticles with proper physico-chemical properties were obtained. The lyophilization process was found to cause a decrease in zeta potential and an increase in PdI as well as and a decrease in entrapment efficiency (EE%) and loading efficiency (LE%) but conservation in size of nanoparticles. Atomic force microscopy (AFM) images showed non-aggregated, stable and spherical to sub-spherical nanoparticles. The in vitro release study revealed higher release rates for lyophilized compared to non-lyophilized nanoparticles. Cytotoxicity studies on Caco-2 cells revealed no significant cytotoxicity for prepared nanoparticles after 3-h post-incubation but did show the concentration-dependent cytotoxicity after 24?h. The percentage of cumulative insulin determined from ex vivo studies was significantly higher in nanoparticles prepared from quaternized aromatic derivatives of chitosan. In vivo data showed significantly higher insulin intestinal absorption in nanoparticles prepared from methylated N-(4-N, N-dimethylaminobenzyl) chitosan nanoparticles compared to trimethyl chitosan.

Conclusion: These data obtained demonstrated that as the result of optimized physico-chemical properties, drug release rate, cytotoxicity profile, ex vivo permeation enhancement and increased in vivo absorption, nanoparticles prepared from N-aryl derivatives of chitosan can be considered as valuable method for the oral delivery of insulin.