Zhouhua Wang

Cubic phase nanoparticles for sustained release of ibuprofen: formulation, characterization, and enhanced bioavailability study

In order to improve the oral bioavailability of ibuprofen, ibuprofen-loaded cubic nanoparticles were prepared as a delivery system for aqueous formulations. The cubic inner structure was verified by cryogenic transmission electron microscopy. With an encapsulation efficiency greater than 85%, the ibuprofen-loaded cubic nanoparticles had a narrow size distribution around a mean size of 238 nm. Differential scanning calorimetry and X-ray diffraction determined that ibuprofen was in an amorphous and molecular form within the lipid matrix. The in vitro release of ibuprofen from cubic nanoparticles was greater than 80% at 24 hours, showing sustained characteristics. The pharmacokinetic study in beagle dogs showed improved absorption of ibuprofen from cubic nanoparticles compared to that of pure ibuprofen, with evidence of a longer half-life and a relative oral bioavailability of 222% (P < 0.05). The ibuprofen-loaded cubic nanoparticles provide a promising carrier candidate with an efficient drug delivery for therapeutic treatment.

Formulation and delivery of improved amorphous fenofibrate solid dispersions prepared by thin film freezing

The objective of this study was to prepare amorphous fenofibrate (FB) solid dispersions using thin film freezing (TFF) and to incorporate the solid dispersions into pharmaceutically acceptable dosage forms. FB solid dispersions prepared with optimized drug/polymer ratios were characterized by modulated differential scanning calorimetry (MDSC), powder X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) specific surface area measurements, Fourier-transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), and supersaturation dissolution testing. Furthermore, a dry granulation technique was used to encapsulate the TFF compositions for in vitro dissolution and in vivo animal pharmacokinetic studies. The results showed that the TFF process produced amorphous, porous, microstructured, and stable solid dispersions with high surface areas. Development of solid oral dosage forms revealed that the performance of the FB containing solid dispersions was not affected by the formulation process, which was confirmed by DSC and XRD. Moreover, an in vivo pharmacokinetic study in rats revealed a significant increase in FB absorption compared to bulk FB. We confirmed that amorphous solid dispersions with large surface areas produced by the TFF process displayed superior dissolution rates and corresponding enhanced bioavailability of the poorly water-soluble drug, FB.

Increasing the oral bioavailability of poorly water-soluble carbamazepine using immediate-release pellets supported on SBA-15 mesoporous silica

Background and methods: The aim of this study was to develop an immediate-release pellet formulation with improved drug dissolution and adsorption. Carbamazepine, a poorly water-soluble drug, was adsorbed into mesoporous silica (SBA-15-CBZ) via a wetness impregnation method and then processed by extrusion/spheronization into pellets. Physicochemical characterization of the preparation was carried out by scanning electron microscopy, transmission electron microscopy, nitrogen adsorption, small-angle and wide-angle x-ray diffraction, and differential scanning calorimetry. Flowability and wettability of the drug-loaded silica powder were evaluated by bulk and tapped density and by the angle of repose and contact angle, respectively. The drug-loaded silica powder was formulated into pellets to improve flowability. Results: With maximum drug loading in SBA-15 matrices determined to be 20% wt, in vitro release studies demonstrated that the carbamazepine dissolution rate was notably improved from both the SBA-15 powder and the corresponding pellets as compared with the bulk drug. Correspondingly, the oral bioavailability of SBA-15-CBZ pellets was increased considerably by 1.57-fold in dogs (P < 0.05) compared with fast-release commercial carbamazepine tablets. Conclusion: Immediate-release carbamazepine pellets prepared from drug-loaded silica provide a feasible approach for development of a rapidly acting oral formulation for this poorly water-soluble drug and with better absorption.

Fabrication and characterization of silk fibroin-coated liposomes for ocular drug delivery

The unique structure and protective mechanisms of the eye result in low bioavailability of ocular drugs. Using a mucoadhesive material is an efficient solution to improve ocular drug therapeutic efficacy. This study was designed to prepare a liposomal formulation coated by a novel adhesive excipient, silk fibroin (SF), for topical ocular drug delivery. The regenerated silk fibroins (SFs) with different dissolving time were coated onto the ibuprofen-loaded liposomes. The morphology, drug encapsulation efficiency, in vitro release and in vitro corneal permeation of SF-coated liposomes (SLs) were investigated in comparison with the conventional liposome. Cellular adhesion and cytotoxicity assay of SF and SLs were tested using human corneal epithelial cells (HCEC). SLs showed sustained drug release and in vitro corneal permeation of ibuprofen as compared to drug solution and conventional liposome. The cellular fluorescence appeared after 7 min of exposure to SF, and the intensity increased sustainedly up to 12h with no detectable cytotoxicity. Higher fluorescence intensity of Nile red in SLs was observed in a short period of 15 min showing a rapid uptake. These favorable properties make SF-coated liposome be a promising ocular drug delivery system.

In vitro and in vivo evaluation of ordered mesoporous silica as a novel adsorbent in liquisolid formulation

Background A liquisolid technique has been reported to be a new approach to improve the release of poorly water-soluble drugs for oral administration. However, an apparent limitation of this technique is the formulation of a high dose because a large amount of liquid vehicle is needed, which finally results in a low-dose liquisolid formulation. Silica as an absorbent has been used extensively in liquisolid formulations. Although nanoparticle silica can be prepared and used to improve liquid adsorption capacity, loading a high dose of drug into a liquisolid is still a challenge. With the aim of improving adsorption capacity and accordingly achieving high drug loading, ordered mesoporous silica with a high surface area and narrow pore size distribution was synthesized and used in a liquisolid formulation. Methods Ordered mesoporous silica was synthesized and its particle size and morphology were tailored by controlling the concentration of cetyltrimethyl ammonium bromide. The ordered mesoporous silica synthesized was characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, small-angle x-ray diffraction, wide angle x-ray diffraction, and nitrogen adsorption-desorption measurements. The liquid adsorption capacity of ordered mesoporous silica was subsequently compared with that of conventional silica materials using PEG400 as the model liquid. Carbamazepine was chosen as a model drug to prepare the liquisolid formulation, with ordered mesoporous silica as the adsorbent material. The preparation was evaluated and compared with commercially available fast-release carbamazepine tablets in vitro and in vivo. Results Characterization of the ordered mesoporous silica synthesized in this study indicated a huge Brunauer–Emmett–Teller surface area (1030 m2/g), an ordered mesoporous structure with a pore size of 2.8 nm, and high adsorption capacity for liquid compared with conventional silica. Compared with fast-release commercial carbamazepine tablets, drug release from the liquisolid capsules was greatly improved, and the bioavailability of the liquisolid preparation was enhanced by 182.7%. Conclusion Ordered mesoporous silica is a potentially attractive adsorbent which may lead to a new approach for development of liquisolid products.

Erratum to: Lactosaminated mesoporous silica nanoparticles for asialoglycoprotein receptor targeted anticancer drug delivery

© 2015 Quan et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Erratum to: J Nanobiotechnol DOI 10.1186/s12951‐015‐0068‐6 Panel A, B, and C from Figure 7 (Fig. 1 here) of this work [1] was generated using HepG2, SMMC7721, and NIH 3T3 cells, respectively. After publication of this work, we noted that they were inadvertently labelled as NIH 3T3, HepG2 and SMMC7721 cells. The figure caption of Figure 7 has now been corrected in this erratum.

Preparation and in vitro evaluation of silk fibroin microspheres produced by a novel ultra-fine particle processing system

The objective of this study was to prepare silk fibroin SF microspheres containing the enhanced green fluorescent protein (EGFP) by using a novel ultra-fine particle processing system (UPPS) and to evaluate the microspheres as possible carriers for long-term delivery of sensitive biologicals. The drug content, encapsulation efficiency, and in vitro release were evaluated by Microplate Absorbance Reader. The particle size distribution and morphology of the microspheres were analyzed by Malvern Master Sizer 2000 and scanning electron microscopy. The distribution of EGFP and the interactions between SF and EGFP were investigated by Confocal Laser Scanning Microscopy, FTIP, Raman and NMR spectroscopy. The results showed that spherical microspheres with narrow size distribution, glossy and dense surface were successfully manufactured by using UPPS technology and over 95% of EGFP encapsulation efficiency and uniform drug distribution in the microspheres were achieved. Furthermore, a burst free and sustained release of encapsulated EGFP for a period of 50 days in deionized water was obtained. In conclusion, the novel UPPS technology could be used to manufacture SF matrix microspheres as a potential long-term protein delivery system to improve patient compliance and convenience.

Molecular Modeling-Based Inclusion Mechanism and Stability Studies of Doxycycline and Hydroxypropyl-β-Cyclodextrin Complex for Ophthalmic Delivery

The aim of the present study was to prepare a stable complex of doxycycline (Doxy) and hydroxypropyl-β-cyclodextrin (HPβCD) for ophthalmic delivery and investigate the inclusion mechanism and the inclusion effects on the stability of Doxy. The Doxy/HPβCD complex was prepared by solution stirring and then characterized by scanning electron microscopy and ultraviolet spectroscopy. Based on results of nuclear magnetic resonance, molecular model of Doxy/HPβCD complex was established using computational simulation of PM3 method implemented in Gaussian 03. Stabilities of Doxy/HPβCD complex in both aqueous solution and solid state at 25°C were evaluated by HPLC. Finally, in vitro antibacterial activity of the Doxy/HPβCD complex was evaluated by disk diffusion test. It was found that the stabilities of Doxy/HPβCD complex in both aqueous solution and solid state were improved obviously as compared with Doxy alone. This stability enhancement is consistent with the inclusion mechanism between HPβCD and Doxy, which showed that the unstable site of Doxy molecule at 6-CH3 was protected in the hydrophobic cavity of HPβCD, additionally, the chelation of Mg2+ provided a synergetic protection of the other unstable site of Doxy at 4-N(CH3)2. The antibacterial activity results indicated that Doxy/HPβCD complex might have potential for clinical applications.

Formulation and evaluation of novel reverse microemulsions containing salmon calcitonin in hydrofluoroalkane propellants

To develop reverse microemulsion as a potential strategy for pulmonary delivery of salmon calcitonin (sCT) in HFA134a propellant of pressurized metered dose inhalers (pMDIs), pluronic P85 (P85) was chosen as the most appropriate surfactant to form microemulsions containing sCT. Formulation parameters, including the surfactant and ethanol content, water content, and sCT loading, were optimized to obtain two desired pMDI formulations A and B with clear and transparent appearance, Tyndall effect, good physical stability and aerosolization properties. Aerosolization properties of the optimized pMDIs were assessed by next generation impactor (NGI) and twin-stage impactor (TSI), and the dose of sCT in each stage was assayed by HPLC. The fine particle fraction (FPF) of formulations A and B were both at the range of approximately 28.0-36.0%. Cytotoxicity studies indicated the cell viability determined by MTT assay only slightly dropped when the A549 cells were exposed to the pMDI formulations. Pharmacological study performed on the male Wistar rats showed the intratracheal administration of the microemulsion pMDIs containing sCT exhibited similar but prolonged hypocalcemic activity compared with the intravenous injection of sCT solution. Therefore, such reverse microemulsions are potential for pulmonary delivery of therapeutic peptides using HFA-pMDIs.

Process Investigation of a Novel Compaction Technique With Pellet-Containing Granules:

Objective: The purpose of this study was to investigate the influence of the preparing process on the properties of pellet-containing granules and tablets. Methods: Coated pellets were granulated by centrifugal granulation, and the obtained pellet-containing granules were mixed with cushioning granules and compressed into tablets. Tablets were characterized for a drug release rate as compared with the original coated pellets. Results: The surface roughness and the angle of repose of pellet-containing granules increased with the granulating ratio. Weight and drug content variations in tablets were diminished by granulation, and great improvement in tablet uniformity was achieved even for large pellets. Granulation showed protection for coated films under different compress forces and at even a low content of cushioning granules. Conclusions: The uniformity of tablets prepared from pellet-containing granules could be significantly improved by the granulation process at a proper granulating ratio. The granulation process could protect the coated pellets during compaction even under high compression forces and with a low content of cushioning granules.