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3319 KiB

Open AccessArticle

On Identification of Critical Material Attributes for Compression Behaviour of Pharmaceutical Diluent Powders

by Jianyi Zhang, Chuan-Yu Wu, Xin Pan and Chuanbin Wu

Materials 2017, 10(7), 845; https://doi.org/10.3390/ma10070845 - 23 Jul 2017

Cited by 37 | Viewed by 5999

Abstract

As one of the commonly-used solid dosage forms, pharmaceutical tablets have been widely used to deliver active drugs into the human body, satisfying patient’s therapeutic requirements. To manufacture tablets of good quality, diluent powders are generally used in formulation development to increase the [...] Read more.

As one of the commonly-used solid dosage forms, pharmaceutical tablets have been widely used to deliver active drugs into the human body, satisfying patient’s therapeutic requirements. To manufacture tablets of good quality, diluent powders are generally used in formulation development to increase the bulk of formulations and to bind other inactive ingredients with the active pharmaceutical ingredients (APIs). For formulations of a low API dose, the drug products generally consist of a large fraction of diluent powders. Hence, the attributes of diluents become extremely important and can significantly influence the final product property. Therefore, it is essential to accurately characterise the mechanical properties of the diluents and to thoroughly understand how their mechanical properties affect the manufacturing performance and properties of the final products, which will build a sound scientific basis for formulation design and product development. In this study, a comprehensive evaluation of the mechanical properties of the widely-used pharmaceutical diluent powders, including microcrystalline cellulose (MCC) powders with different grades (i.e., Avicel PH 101, Avicel PH 102, and DG), mannitol SD 100, lactose monohydrate, and dibasic calcium phosphate, were performed. The powder compressibility was assessed with Heckel and Kawakita analyses. The material elastic recovery during decompression and in storage was investigated through monitoring the change in the dimensions of the compressed tablets over time. The powder hygroscopicity was also evaluated to examine the water absorption ability of powders from the surroundings. It was shown that the MCC tablets exhibited continuous volume expansion after ejection, which is believed to be induced by (1) water absorption from the surrounding, and (2) elastic recovery. However, mannitol tablets showed volume expansion immediately after ejection, followed by the material shrinkage in storage. It is anticipated that the expansion was induced by elastic recovery to a limited extent, while the shrinkage was primarily due to the solidification during storage. It was also found that, for all powders considered, the powder compressibility and the elastic recovery depended significantly on the particle breakage tendency: a decrease in the particle breakage tendency led to a slight decrease in the powder compressibility and a significant drop in immediate elastic recovery. This implies that the particle breakage tendency is a critical material attribute in controlling the compression behaviour of pharmaceutical powders. Full article

(This article belongs to the Special Issue Materials for Drug Delivery and Biomedical Consideration)

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3117 KiB

Open AccessArticle

Improved Gene Transfer with Functionalized Hollow Mesoporous Silica Nanoparticles of Reduced Cytotoxicity

by Zhengwen Zhan, Xiaoxu Zhang, Jiayuan Huang, Ying Huang, Zhengwei Huang, Xin Pan, Guilan Quan, Hu Liu, Lili Wang and And Chuanbin Wu

Materials 2017, 10(7), 731; https://doi.org/10.3390/ma10070731 - 30 Jun 2017

Cited by 13 | Viewed by 5024

Abstract

Gene therapy is a promising strategy for treatment of genetically caused diseases. Successful gene delivery requires an efficient carrier to transfer the desired gene into host cells. Recently, mesoporous silica nanoparticles (MSNs) functionalized with 25 kD polyethyleneimine (PEI) were extensively used as gene [...] Read more.

Gene therapy is a promising strategy for treatment of genetically caused diseases. Successful gene delivery requires an efficient carrier to transfer the desired gene into host cells. Recently, mesoporous silica nanoparticles (MSNs) functionalized with 25 kD polyethyleneimine (PEI) were extensively used as gene delivery carriers. However, 25 kD PEI could significantly reduce the safety of the modified MSNs although it is efficient for intracellular delivery of nucleic acids. In addition, limited drug loading remains a challenge for conventional MSNs drug carriers. Hollow mesoporous silica nanoparticles (HMSNs) with high pore volume, tunable pore size, and excellent biocompatibility are attractive alternatives. To make them more efficient, a less toxic 1.8 kD PEI polymer was used to functionalize the HMSNs which have large pore size (~10 nm) and form PEI-HMSNs. Scanning and transmission electron microscopic images showed that HMSNs were spherical in shape and approximately 270 nm in diameter with uniform hollow nanostructures. The maximum loading capacity of green fluorescent protein labeled DNA (GFP-DNA) in PEI-HMSNs was found to be 37.98 mg/g. The loading capacity of PEI-HMSNs was nearly three-fold higher than those of PEI modified solid nanoparticles, indicating that both hollow and large pores contributed to the increase in DNA adsorption. The transfection of GFP-DNA plasmid loaded in PEI-HMSNs was increased two-fold in comparison to that of 25 kD PEI. MTT assays in Lovo cells showed that the cell viability was more than 85% when the concentration of PEI-HMSNs was 120 µg/mL, whereas the cell viability was less than 20% when the 25 kD PEI was used at the same concentration. These results indicated that PEI-HMSNs could be used as a delivery system for nucleic acids due to good biocompatibility, high gene loading capacity, and enhanced gene transfer efficiency. Full article

(This article belongs to the Special Issue Materials for Drug Delivery and Biomedical Consideration)

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3181 KiB

Open AccessArticle

The Effects of Relative Humidity on the Flowability and Dispersion Performance of Lactose Mixtures

by Xiang-Yun Lu, Lan Chen, Chuan-Yu Wu, Hak-Kim Chan and Tim Freeman

Materials 2017, 10(6), 592; https://doi.org/10.3390/ma10060592 - 29 May 2017

Cited by 32 | Viewed by 5424

Abstract

The flowability and dispersion behavior are two important physicochemical properties of pharmaceutical formulations for dry powder inhalers (DPIs). They are usually affected by the environmental conditions, such as temperature and relative humidity (RH). However, very few studies have been focused on the relationship [...] Read more.

The flowability and dispersion behavior are two important physicochemical properties of pharmaceutical formulations for dry powder inhalers (DPIs). They are usually affected by the environmental conditions, such as temperature and relative humidity (RH). However, very few studies have been focused on the relationship between the two properties and their dependence on RH during storage. In this research, model pharmaceutical formulations were prepared using mixtures of coarse and fine lactose. The fractions of fines in the mixtures were 0%, 5%, 10%, and 20%, respectively. These blends were stored at four different RH levels, 0%, 30%, 58%, and 85%, for 48 h. The FT4 Powder Rheometer was used to evaluate the powder flowability, and the Malvern Spraytec^® laser diffraction system was employed to assess the powder dispersion performance. The results indicated that both the flow and dispersion properties of lactose blends deteriorate after being stored at 85% RH, but improved after being conditioned at 58% RH. The fine particle fractions (FPFs) of the blends with 5% and 10% fine fractions and the as-received coarse lactose decreased when they were conditioned at 30% RH. For the blend with 20% fine fraction, a high RH during storage (i.e., 85% RH) affected the dispersion property, but had a limited influence on its flowability, while, for the coarse lactose powder, the different RH conditions affected its flowability, but not the dispersion results. A strong correlation between the powder flowability and its dispersion performance was found. Full article

(This article belongs to the Special Issue Materials for Drug Delivery and Biomedical Consideration)

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3340 KiB

Open AccessArticle

The Correlation of Pore Size and Bioactivity of Spray-Pyrolyzed Mesoporous Bioactive Glasses

by Yu-Jen Chou, Bo-Jiang Hong, Ying-Chih Lin, Chen-Ying Wang and Shao-Ju Shih

Materials 2017, 10(5), 488; https://doi.org/10.3390/ma10050488 - 3 May 2017

Cited by 11 | Viewed by 4234

Abstract

SiO₂–CaO–P₂O₅-based mesoporous bioactive glasses (MBGs) were synthesized by spray pyrolysis in this study. Three commonly used non-ionic tri-block copolymers (L121, P123, and F127) with various lengths of hydrophilic chains were applied as structural templates to achieve different [...] Read more.

SiO₂–CaO–P₂O₅-based mesoporous bioactive glasses (MBGs) were synthesized by spray pyrolysis in this study. Three commonly used non-ionic tri-block copolymers (L121, P123, and F127) with various lengths of hydrophilic chains were applied as structural templates to achieve different pore sizes. A mesoporous structure was observed in each as-prepared specimen, and the results showed that the L121-treated MBG had the largest pore size. The results of bioactivity tests indicated that the growth of hydroxyapatite is related to the pore size of the materials. Full article

(This article belongs to the Special Issue Materials for Drug Delivery and Biomedical Consideration)

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9485 KiB

Open AccessArticle

Preparation, Characterization and Application of a Molecularly Imprinted Polymer for Selective Recognition of Sulpiride

by Wei Zhang, Xuhui She, Liping Wang, Huajun Fan, Qing Zhou, Xiaowen Huang and James Z. Tang

Materials 2017, 10(5), 475; https://doi.org/10.3390/ma10050475 - 28 Apr 2017

Cited by 48 | Viewed by 6115

Abstract

A novel molecular imprinting polymer (MIP) was prepared by bulk polymerization using sulpiride as the template molecule, itaconic acid (ITA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the crosslinker. The formation of the MIP was determined as the molar ratio [...] Read more.

A novel molecular imprinting polymer (MIP) was prepared by bulk polymerization using sulpiride as the template molecule, itaconic acid (ITA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the crosslinker. The formation of the MIP was determined as the molar ratio of sulpiride-ITA-EGDMA of 1:4:15 by single-factor experiments. The MIP showed good adsorption property with imprinting factor α of 5.36 and maximum adsorption capacity of 61.13 μmol/g, and was characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR) and surface area analysis. With the structural analogs (amisulpride, tiapride, lidocaine and cisapride) and small molecules containing a mono-functional group (p-toluenesulfonamide, formamide and 1-methylpyrrolidine) as substrates, static adsorption, kinetic adsorption, and rebinding experiments were also performed to investigate the selective adsorption ability, kinetic characteristic, and recognition mechanism of the MIP. A serial study suggested that the highly selective recognition ability of the MIP mainly depended on binding sites provided by N-functional groups of amide and amine. Moreover, the MIP as solid-phase extractant was successfully applied to extraction of sulpiride from the mixed solution (consisted of p-toluenesulfonamide, sulfamethoxazole, sulfanilamide, p-nitroaniline, acetanilide and trimethoprim) and serum sample, and extraction recoveries ranged from 81.57% to 86.63%. The tentative tests of drug release in stimulated intestinal fluid (pH 6.8) demonstrated that the tablet with the MIP–sulpiride could obviously inhibit sulpiride release rate. Thus, ITA-based MIP is an efficient and promising alternative to solid-phase adsorbent for extraction of sulpiride and removal of interferences in biosample analysis, and could be used as a potential carrier for controlled drug release. Full article

(This article belongs to the Special Issue Materials for Drug Delivery and Biomedical Consideration)

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2774 KiB

Open AccessArticle

Investigating the Effects of Loading Factors on the In Vitro Pharmaceutical Performance of Mesoporous Materials as Drug Carriers for Ibuprofen

by Junmin Lai, Wu Lin, Peter Scholes and Mingzhong Li

Materials 2017, 10(2), 150; https://doi.org/10.3390/ma10020150 - 9 Feb 2017

Cited by 31 | Viewed by 5191

Abstract

The aim of the study was to investigate the effects of the loading factors, i.e., the initial drug loading concentration and the ratio of the drug to carriers, on the in vitro pharmaceutical performance of drug-loaded mesoporous systems. Ibuprofen (IBU) was used as [...] Read more.

The aim of the study was to investigate the effects of the loading factors, i.e., the initial drug loading concentration and the ratio of the drug to carriers, on the in vitro pharmaceutical performance of drug-loaded mesoporous systems. Ibuprofen (IBU) was used as a model drug, and two non-ordered mesoporous materials of commercial silica Syloid^® 244FP (S244FP) and Neusilin^® US2 (NS2) were selected in the study. The IBU-loaded mesoporous samples were prepared by a solvent immersion method with a rotary evaporation drying technique and characterized by polarized light microscopy (PLM), Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Dissolution experiments were performed in simulated gastric media at 37 °C under non-sink conditions. The concentration of IBU in solution was determined by HPLC. The study showed that the dissolution rate of IBU can be improved significantly using the mesoporous S224FP carriers due to the conversion of crystalline IBU into the amorphous form. Both of the loading factors affected the IBU dissolution kinetics. Due to the molecular interaction between the IBU and NS2 carriers, the loading factors had little effects on the drug release kinetics with incomplete drug desorption recovery and insignificant dissolution enhancement. Care and extensive evaluation must therefore be taken when mesoporous materials are chosen as carrier delivery systems. Full article

(This article belongs to the Special Issue Materials for Drug Delivery and Biomedical Consideration)

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1152 KiB

Open AccessArticle

Nonionic Microemulsions as Solubilizers of Hydrophobic Drugs: Solubilization of Paclitaxel

by Jen-Ting Lo, Tzer-Min Lee and Bing-Hung Chen

Materials 2016, 9(9), 761; https://doi.org/10.3390/ma9090761 - 7 Sep 2016

Cited by 10 | Viewed by 5737

Abstract

The strategy using nonionic microemulsion as a solubilizer for hydrophobic drugs was studied and is demonstrated in this work. The aqueous phase behaviors of mixed nonionic surfactants with various oils at 37 °C are firstly constructed to give the optimal formulations of nonionic [...] Read more.

The strategy using nonionic microemulsion as a solubilizer for hydrophobic drugs was studied and is demonstrated in this work. The aqueous phase behaviors of mixed nonionic surfactants with various oils at 37 °C are firstly constructed to give the optimal formulations of nonionic microemulsions with applications in the enhanced solubilization of the model hydrophobic drug, paclitaxel, at 37 °C. Briefly, the suitable oil phase with paclitaxel significantly dissolved is microemulsified with appropriate surfactants. Surfactants utilized include Tween 80, Cremophor EL, and polyethylene glycol (4.3) cocoyl ether, while various kinds of edible oils and fatty esters are used as the oil phase. On average, the apparent solubility of paclitaxel is increased to ca. 70–100 ppm in the prepared microemulsions at 37 °C using tributyrin or ethyl caproate as the oil phases. The sizes of the microemulsions attained are mostly from ca. 60 nm to ca. 200 nm. The cytotoxicity of the microemulsion formulations is assessed with the cellular viability of 3T3 cells. In general, the cell viability is above 55% after 24 h of cultivation in media containing these microemulsion formulations diluted to a concentration of total surfactants equal to 50 ppm and 200 ppm. Full article

(This article belongs to the Special Issue Materials for Drug Delivery and Biomedical Consideration)

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Review

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2710 KiB

Open AccessFeature PaperReview

Protein-Based Drug-Delivery Materials

by Dave Jao, Ye Xue, Jethro Medina and Xiao Hu

Materials 2017, 10(5), 517; https://doi.org/10.3390/ma10050517 - 9 May 2017

Cited by 129 | Viewed by 11167

Abstract

There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based [...] Read more.

There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function—including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments—are summarized at the end of this review. Full article

(This article belongs to the Special Issue Materials for Drug Delivery and Biomedical Consideration)

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