Low Drug Release Research Articles

Bilayered buccal films as child-appropriate dosage form for systemic administration of propranolol

Buccal mucosa has emerged as an attractive site for systemic administration of drug in paediatric patients. This route is simple and non-invasive, even if the saliva wash-out effect and the relative permeability of the mucosa can reduce drug absorption. Mucoadhesive polymers represent a common employed strategy to increase the contact time of the formulation at the application site and to improve drug absorption. Among the different mucoadhesive dosage forms, buccal films are particularly addressed for paediatric population since they are thin, adaptable to the mucosal surface and able to offer an exact and flexible dose. The objective of the present study was to develop bilayered buccal films for the release of propranolol hydrochloride. A primary polymeric layer was prepared by casting and drying of solutions of film-forming polymers, such as polyvinylpyrrolidone (PVP) or polyvinylalcohol (PVA), added with different weight ratios of gelatin (GEL) or chitosan (CH). In order to achieve unidirectional drug delivery towards buccal mucosa, a secondary ethylcellulose layer was applied onto the primary layer. Bilayered films were characterized for their physico-chemical (morphology, thickness, drug content and solid state) and functional (water uptake, mucoadhesion, drug release and permeation) properties. The inclusion of CH into PVP and PVA primary layer provided the best mucoadhesion ability. Films containing CH provided a lower drug release with respect to films containing GEL and increased the amount of permeated drug through buccal mucosa, thanks to its ability of interfering with the lipid organization. The secondary ethylcellulose layer did not interfere with drug permeation, but it could limit drug release in the buccal cavity.

Electrospun collagen-based nanofibres: A sustainable material for improved antibiotic utilisation in tissue engineering applications

For the creation of scaffolds in tissue engineering applications, it is essential to control the physical morphology of fibres and to choose compositions which do not disturb normal physiological function. Collagen, the most abundant protein in the human body, is a well-established biopolymer used in electrospinning compositions. It shows high in-vivo stability and is able to maintain a high biomechanical strength over time. In this study, the effects of collagen type I in polylactic acid-drug electrospun scaffolds for tissue engineering applications are examined. The samples produced were subsequently characterised using a range of techniques. Scanning electron microscopy analysis shows that the fibre morphologies varied across PLA-drug and PLA-collagen-drug samples − the addition of collagen caused a decrease in average fibre diameter by nearly half, and produced nanofibres. Atomic force microscopy imaging revealed collagen-banding patterns which show the successful integration of collagen with PLA. Solid-state characterisation suggested a chemical interaction between PLA and drug compounds, irgasan and levofloxacin, and the collagen increased the amorphous regions within the samples. Surface energy analysis of drug powders showed a higher dispersive surface energy of levofloxacin compared with irgasan, and contact angle goniometry showed an increase in hydrophobicity in PLA-collagen-drug samples. The antibacterial studies showed a high efficacy of resistance against the growth of both E. coli and S. Aureus, except with PLA-collagen-LEVO which showed a regrowth of bacteria after 48h. This can be attributed to the low drug release percentage incorporated into the nanofibre during the in vitro release study. However, the studies did show that collagen helped shift both drugs into sustained release behaviour. These ideal modifications to electrospun scaffolds may prove useful in further research regarding the acceptance of human tissue by inhibiting the potential for bacterial infection.

Biodegradable Micelles Based on Poly(ethylene glycol)-b-polylipopeptide Copolymer: A Robust and Versatile Nanoplatform for Anticancer Drug Delivery.

Poly(ethylene glycol)-b-polypeptide block copolymer micelles, with excellent safety, are one of the most clinically studied nanocarriers for anticancer drug delivery. Notably, self-assembled nanosystems based on hydrophobic polypeptides showing typically a low drug loading and burst drug release are limited to preclinical studies. Here, we report that poly(ethylene glycol)-b-poly(α-aminopalmitic acid) (PEG-b-PAPA) block copolymer could be easily prepared with tailored Mn through ring-opening polymerization of α-aminopalmitic acid N-carboxyanhydride (APA-NCA). Interestingly, PEG-b-PAPA copolymers exhibited superb solubility in common organic solvents (including CHCl3, CH2Cl2, and THF), while stable nanomicelles were formed in phosphate buffer, with a small size of 59 nm and a low critical micelle concentration of 2.38 mg/L. These polylipopeptide micelles (Lipep-Ms) allowed facile loading of a potent anticancer drug, docetaxel (DTX), likely due to the existence of a strong interaction between the lipophilic drug and polylipopeptide in the core. Notably, cRGD-peptide-functionalized Lipep-Ms (cRGD-Lipep-Ms) were also obtained with similar biophysical characteristics. The in vitro studies showed efficient cellular uptake of DTX-loaded cRGD-Lipep-Ms by B16F10 cells and fast intracellular drug release due to the enzymatic degradation of PAPA blocks in endo/lysosome, leading to a pronounced anticancer effect (IC50 = 0.15 μg DTX equiv/mL). The in vivo therapy studies showed that DTX-cRGD-Lipep-Ms exhibited superior tumor growth inhibition of B16F10 melanoma, improved survival rate, and little side effects as compared to free DTX. These polylipopeptide micelles appear as a promising and robust nanoplatform for anticancer drug delivery.

Electrospinning and crosslinking of polyvinyl alcohol/chitosan composite nanofiber for transdermal drug delivery

AbstractThe drug‐loaded polyvinyl alcohol (PVA)/chitosan (CS) composite nanofibers intended to be used as matrix for transdermal drug delivery were fabricated by electrospinning, and then crosslinked through glulataraldehyde (GA). The morphology, chemical structure, thermal behavior, mechanical properties, hydrophilicity and drug release properties of drug‐loaded PVA/CS composite nanofibers before and after crosslinking were characterized. The results showed that the morphology of PVA/CS composite nanofibers was not been destroyed in both crosslinking and in vitro drug release process. The Young's modulus, tensile strength, thermal properties and hydrophobicity of crosslinked PVA/CS composite nanofibers significantly increased in comparison with those of PVA/CS (without crosslinking) due to the formation of crosslinking network structure. In vitro release studies showed that crosslinked PVA/CS composite nanofibers had lower drug release rate and smaller amount of drug burst release than that of PVA/CS. According to release exponent “n”, the release of ampicillin sodium from crosslinked PVA/CS composite nanofibers fit to the Fickian diffusion mechanism. Those results demonstrate the potential utilization of crosslinked PVA/CS composite nanofibers as a transdermal drug delivery system.

Synthesis and Characterization of Dual-Sensitive Fluorescent Nanogels for Enhancing Drug Delivery and Tracking Intracellular Drug Delivery.

Here, dual-sensitive fluorescent branched alginate-polyethyleneimine copolymer (bAPSC) nanogels were synthesized from thiolated alginate and stearoyl-derivatized branched polyethyleneimine. The formation of bAPSC conjugates was confirmed through proton nuclear magnetic resonance and Fourier transform infrared spectroscopy, whereas dynamic light scattering was used to measure the particle size and ζ potential of the nanogels. The fluorescent properties of the nanogels were confirmed through fluorescent spectroscopy and microscopy. In addition to the excitation-dependent fluorescence behavior, the fluorescence emission intensity of bAPSC was altered by both pH and γ-irradiation. This intensity was higher at a lower pH than at a higher pH, and it slightly decreased after γ-irradiation. The drug loading and encapsulation efficiency of bAPSC were 25.9% and 11.2%, respectively. An in vitro drug release study revealed that the synthesized nanogels release their doxorubicin (Dox) contents in a time-dependent manner, and the drug release was higher after 96 h of incubation. Approximately 43.74% and 88.36% of Dox was released after 96 h of incubation at pH 5.5 in the absence and presence of glutathione (GSH), respectively. However, relatively lower drug release, approximately 21.6% and 16%, was observed in the presence and absence of GSH at pH 7.4, respectively. Fluorescence microscopy confirmed that Dox-loaded bAPSC nanogels were internalized by HeLa cells, and drug distribution was easily tracked using fluorescent materials without additional probing agents. Moreover, cellular cytotoxicity and hemolysis results revealed less cytotoxicity and hemocompatibility of the synthesized nanogels, confirming that they are the most favorable alternative drug carriers for drug delivery systems.

New doxorubicin nanocarriers based on cyclodextrins.

Polymeric nanoparticles and fibrin gels (FBGs) are attractive biomaterials for local delivery of a variety of biotherapeutic agents, from drugs to proteins. We combined these different drug delivery approaches by preparing nanoparticle-loaded FBGs characterized by their intrinsic features of drug delivery rate and antiproliferative/apoptotic activities. Inclusion complexes of doxorubicin (DOXO) with oligomeric β-cyclodextrins (oCyD) functionalized with different functional groups were studied. These nanocarriers were able to interact with FBGs as shown by a decreased release rate of DOXO. One of these complexes, oCyDNH2/DOXO, demonstrated good antiproliferative and apoptotic activity in vitro, reflecting a higher drug uptake by cells. As hypothesized, the nanocarrier/FBG complexes showed a lower drug release rate than similar FBGs loaded with the corresponding non-functionalized oCyD/DOXO. Taken together, our results provide experimental evidence that oCyDNH2/DOXO complexes may be useful components in enhanced FBGs and further build support for the great promise these complex molecules hold for clinical use in localized anticancer therapy of inoperable or surgically removable tumors of different histological origin.

Physicochemical attributes and dissolution testing of ophthalmic ointments

The investigation of semisolid ophthalmic ointments is challenging due to their complex physicochemical properties and the unique anatomy of the human eye. Using Lotemax® as a model ophthalmic ointment, three different manufacturing processes and two excipient sources (Fisher® (OWP) and Fougera® (NWP)) were used to prepare loteprednol etabonate ointments that were qualitatively and quantitatively the same across the manufactured formulations. Physicochemical properties including drug content and uniformity, particle size and distribution, as well as rheological parameters (onset point, crossover modulus, storage modulus and Power law consistency index) were investigated. In addition, USP apparatus 2 with enhancer cells was utilized to study the in vitro drug release characteristics of the ophthalmic ointments. Both manufacturing processes and excipient sources had a significant influence on the physicochemical attributes and the in vitro drug release profiles of the prepared ointments. Ointments prepared via the hot melt processes exhibited higher rheological parameters and lower drug release rates compared to ointments prepared without hot melting. Ointments prepared with OWP demonstrated higher rheological parameters and lower in vitro drug release rates compared to ointments prepared with NWP. A strong correlation between the rheological parameters and in vitro drug release rate was shown using logarithmic linear regression. This correlation may be useful in predicting in vitro drug release from measured physicochemical properties, and identifying the critical quality attributes during the development of ointment formulations.

Multiple Lipid Nanoparticles (MLN), a New Generation of Lipid Nanoparticles for Drug Delivery Systems: Lamivudine-MLN Experimental Design.

An optimized methodology for the development of a new generation of lipid nanoparticles, the multiple lipid nanoparticles (MLN) is described. MLN have characteristics between nanostructured lipid carriers (NLC) and multiple emulsions (W/O/W), but without the outer aqueous phase. The production is based on a hot homogenization method combined with high shear and ultrasonication. The antiretroviral agent lamivudine (3TC), was loaded in the MLN. For comparison purposes, NLC-3TC formulation was also developed and physico-chemically characterized by the same parameters as MLN-3TC. The development and optimization of MLN and NLC formulations were supported by a Quality by Design (QbD) approach. The MLN-3TC formulation exhibited a size of about 450nm, polydispersity <0.3 and negative zeta potential > -20mV. Furthermore, the morphology assessed by TEM showed a structure with multiples aqueous vacuoles. MLN-3TC was physically stable for at least 45days, had low cytotoxicity and drug release studies showed a sustained and controlled release of 3TC under gastric and plasma-simulated conditions (at pH7.4 for about 45h). The optimized formulations present suitable profiles for oral administration. Overall, the results reveal that MLN present higher loading capacity and storage stability than NLC.

Effects of crystallinity and surface modification of calcium phosphate nanoparticles on the loading and release of tetracycline hydro-chloride

The influences of crystallinity and surface modification of calcium phosphate nanoparticles (nCaP) on their drug loading capacity and drug release profile were studied in the present investigation. The CaP nanoparticles with different crystallinity were prepared by precipitation method under different temperatures. CaP nanoparticles with lower crystallinity exhibited higher drug loading capacity. The samples were characterized by XRD, FT-IR, SEM, TEM and BET surface area analyzer respectively. The drug loading capacity of nCaP was evaluated to tetracycline hydro-chloride (TCH). The internalization of TCH loaded nCaP in cancer cell was observed by florescence microscope. nCaP could be stabilized and dispersed in aqueous solution by poly(acrylic acid) surface modification agent, leading to enhanced drug loading capacity. The drug release was conducted in different pH environment and the experimental data proved that nCaP were pH sensitive drug carrier, suggesting that nCaP could achieve the controlled drug release in intracellular acidic environment. Furthermore, nCaP with higher crystallinity showed lower drug release rate than that of lower crystallinity, indicating that the drug release profile could be adjusted by crystallinity of nCaP. nCaP with adjustable drug loading and release properties are promising candidate as drug carrier for disease treatment.

Self-assembling polyether-b-polymethacrylate graft copolymers loaded with indomethacin

ABSTRACTThe amphiphilic graft copolymers containing polyether-b-polymethacrylate side chains are proposed as carriers for a nonsteroidal anti-inflammatory drug, indomethacin (IMC). Two series of copolymers, poly((methyl methacrylate)-co-(poly(ethylene glycol methacrylate)-graft-poly((methacrylic acid)-co-(tert-butyl methacrylate)))) (P(MMA-co-(PEGMA-graft-P(MAA-co-tBMA)))) and poly((methyl methacrylate)-co-(poly(propylene glycol methacrylate)-graft-poly((methacrylic acid)-co-(tert-butyl methacrylate)))) (P(MMA-co-(PPGMA-graft-P(MAA-co-tBMA)))) were applied in the micellization process. The effects of grafting degree (5–15%), length of the graft polymethacrylic segments (29–186 units), composition (PEG vs. PPG), and content of acidic fraction (52–89%) were verified in the design of two different types of micelles (depending on polyether nature) with proper stability and controlled release of the drug. The methacrylic segment with MAA units resulted in negatively charged layer as it was indicated by measurements of zeta potential (from −2 to −44 mV) The sizes of particles were in the range of 160–225 nm. The type of polyether segment influenced on the content of the drug encapsulation (PEG 39% vs. PPG 93% at 48% of hydrophobic fraction). In vitro experiments demonstrated significantly larger IMC releasing at pH 7.4 than in acidic conditions. The lower drug release rates were monitored for copolymers with long side chains containing large content of acidic units, what enhanced particle stabilization and drug-polymer interactions. The drug release profiles were well fitted to the Higuchi model, suggesting diffusion mechanism. The results confirmed that the graft copolymers might be applied as the carriers releasing a various doses of drug with the rate, which can be adjusted by wider sort of structural parameters than is possible in linear amphiphilic copolymers.

Melt electrospinning vs. solution electrospinning: A comparative study of drug-loaded poly (ε-caprolactone) fibres

Curcumin-loaded poly (ε-caprolactone) (PCL) fibres prepared by melt and solution electrospinning methods were both fabricated to investigate their difference in characterization and drug release behaviour. The increasing curcumin content did not influence the morphologies of melt electrospun fibre, but enhanced the range of diameter distribution of solution electrospun fibre owing to the curcumin aggregates in the spinning solution which disturbed the stability of jet. Moreover, a large amount of curcumin with amorphous state could be loaded in the melt electrospun fibre. Whereas the limited solubility of curcumin in the solvent led to the drug aggregates dispersing within the solution electrospun fibre. In addition, the melt electrospun fibres had low drug release rate without burst release on the profiles due to the high crystallinity in the fibre, but high drug release rate and burst release occurred on the release profiles of the solution electrospun fibres because of their low crystallinity, porous structure and roughness surface.

Intracellular pH-responsive and rituximab-conjugated mesoporous silica nanoparticles for targeted drug delivery to lymphoma B cells

BackgroundOne of the main problems in B cell lymphoma treatment is severe adverse effects and low therapeutic efficacy resulting from systemic chemotherapy. A pH-sensitive controlled drug release system based on mesoporous silica nanoparticles was constructed for targeted drug delivery to tumor cells to reduce systemic toxicity and improve the therapeutic efficacy.MethodsIn this study, the doxorubicin (DOX) was filled into the mesopores of the functional MSNs (DMSNs). Furthermore, rituximab was introduced as the targeted motif of functional DMSNs using an avidin-biotin bridging method to evaluate the targetability to tumor cells. Then, the cell viability and apoptosis efficiency after treatment with rituximab-conjugated DMSNs (RDMSNs) were estimated by using CCK-8 assay and flow cytometry, respectively. Additionally, the research in vivo was performed to evaluate the enhanced antitumor efficacy and the minimal toxic side effects of RDMSNs. Also, TUNEL staining assay was employed to explore the mechanism of antitumor effects of RDMSNs.ResultsThis targeted drug delivery system exhibited low premature drug release at a physiological pH and efficient pH-responsive intracellular release under weakly acidic conditions. The in vitro tests confirmed that targeted RDMSNs could selectively adhere to the surface of lymphoma B cells via specific binding with the CD20 antigen and be internalized into CD20 positive Raji cells but few CD20 negative Jurkat cells, which leads to increased cytotoxicity and apoptosis of the DOX in Raji cells due to the release of the entrapped DOX with high efficiency in the slightly acidic intracellular microenvironment. Furthermore, the in vivo investigations confirmed that RDMSNs could efficiently deliver DOX to lymphoma B cells by pH stimuli, thus inducing cell apoptosis and inhibiting tumor growth, while with minimal toxic side effects.ConclusionsThis targeted and pH-sensitive controlled drug delivery system has the potential for promising application to enhance the therapeutic index and reduce the side effects of B cell lymphoma therapy.

Development of enteric-coated fixed dose combinations of amorphous solid dispersions of ezetimibe and lovastatin: Investigation of formulation and process parameters

Enteric-coated fixed-dose combinations of ezetimibe and lovastatin were prepared by fluid bed coating aiming to avoid the acidic conversion of lovastatin to its hydroxyacid derivative. In a two-step process, sucrose beads were layered with a glass solution of ezetimibe, lovastatin and Soluplus®, top-coated with an enteric layer. The impact of different bead size, enteric polymers (Eudragit L100® and Eudragit L100-55®) and coating time was investigated. Samples were evaluated by X-ray diffraction, scanning electron microscopy, laser diffraction and in vitro studies in 0.1M HCl and phosphate buffer pH 6.8. Results showed that smaller beads tend to agglomerate and release was jeopardized in acidic conditions, most likely due to irregular coating layer. Eudragit L100-55® required longer processing, but thinner coating layers provided lower drug release. Both polymers showed low drug release in acidic environment and fast release at pH 6.8. The off-line measurement of the coating thickness determined the ideal coating time as 15 and 30min for Eudragit L100-55® and Eudragit L100®-based samples, respectively. Both compounds were molecularly dispersed in Soluplus®, and Eudragit L100® formulations showed concave pores on the surface, presenting higher drug release in acidic conditions. Stability studies after 6 months showed unaltered physical properties and drug release.

Development and preliminary characterization of levofloxacin pharmaceutical cocrystals for dissolution rate enhancement

The current investigation aimed to enhance the dissolution rate and mask the bitter taste of levofloxacin by developing pharmaceutical cocrystals using stearic acid and saccharin sodium as coformers. The developed cocrystals were characterized by Fourier transform infrared spectroscopy, which showed the formation of a regular carboxylic acid homosynthon in 1:1 ratio of levofloxacin-stearic acid and carboxylic acid- imide heterosynthon in 2:1 ratio of levofloxacin-saccharin sodium. The existence of the drug in a new crystalline form in the developed cocrystals was confirmed by solid state characterization. The dissolution studies of the developed cocrystals in simulated gastric fluid (pH 1.2) showed significant improvement of the drug dissolution rate (%min−1) from L-ST1 (7.8 ± 0.1) and L-SA2 (7.2 ± 0.4) cocrystals compared to supplied levofloxacin (4.4 ± 0.3). The taste masking ability of L-ST1 and L-SA2 was determined by conducting dissolution studies at salivary pH 6.6 and the results showed a very low drug release of 6.6 ± 0.6% from L-ST1 compared to supplied levofloxacin (64.5 ± 1.5%) and L-SA2 (55.1 ± 1.5%) in 5 min. This study demonstrates that pharmaceutical cocrystals of levofloxacin with stearic acid at 1:1 ratio enhanced the dissolution rate and masked the bitter taste of levofloxacin whereas saccharin sodium has showed only improved dissolution.

The influence of thermal treatment and type of insoluble poly(meth)acrylates on dissolution behavior of very soluble drug from hypromellose matrix tablets evaluated by multivariate data analysis

Hypromellose matrices exhibit extended burst effect immediately after contact with aqueous medium, especially when a water-soluble drug is incorporated. The objective of this study was to reduce burst effect and maintain complete dissolution of a very soluble levetiracetam over 12 h period from hypromellose K4M matrices to obtain zero-order kinetics. Desired changes were achieved by applying water dispersions of insoluble Eudragits® (NE, NM, RL, RS) as a granulation liquid to the drug/microcrystalline cellulose mixture during high-shear granulation (non-thermal treated set) and consequently by thermally treating granules or final tablets (TT), respectively. Applying Eudragit® water dispersions to the drug/microcrystalline cellulose mixture was recognized as an effective method of significantly reducing the burst release (25.4–33.7%) of levetiracetam in comparison with a reference sample without Eudragit®. Multivariate data analysis showed that the addition of Eudragit® reduced burst effect, increased fitting with zero-order kinetics, and supported matrix erosion as the supplementary mechanism to predominant diffusion. Moreover, resulting PCA sub-model revealed the addition of Eudragit® RL and thermal treatment of tablets to be the most suitable method of all. For a 12 h dissolution profile, characterized by low burst effect and drug release close to 100% at the 12th hour, sample RL_TT was the most suitable.

Development of small intestine-specific delivery system for metformin hydrochloride delivery

The aim of this investigation is to design a novel small intestine-specific delivery system of antidiabetes mellitus by coating chitosan on SBA-15 functionalized with COOH groups, and metformin hydrochloride is used as a model drug to study the drug release kinetics of the carriers. The drug loading capacity of the SBA-15-COOH (52.3 wt%) is more than twice as much as the SBA-15 (25.3 wt%). The excellent loading capacity for metformin hydrochloride is attributed to the specific interactions between the –COOH of SBA-15-COOH and the –NH2 of metformin hydrochloride. The release in vitro shows that the metformin hydrochloride is released from Chit/SBA-15-COOH is retarded at low pH 4.0, which is low drug (18 wt%) released. While at pH 7.4, the release rate of metformin hydrochloride could reach 70 wt%, suggesting that the Chit/SBA-15-COOH will be promising for site-specific drug delivery in the intestine. A spherical SBA-15-COOH was prepared by SBA-15 functionalized with COOH groups, and the drug loading capacity of the SBA-15-COOH can reach to 52.3 wt%. After coating the Chit, the system shows a pH sensing control release ability. At low pH condition, there is low drug release; while at high pH condition, the Chit/SBA-15-COOH shows the excellent release profile, suggesting that the Chit/SBA-15-COOH will be promising for site-specific drug delivery in the intestine.

Chitosan-clay matrix tablets for sustained-release drug delivery: Effect of chitosan molecular weight and lubricant

Matrix tablets prepared using chitosan-clay microparticles with various molecular weights (MWs) of chitosan were characterized in terms of hardness, swelling, and drug release. Moreover, the effect of magnesium stearate on the physical properties and drug release of the tablets was also examined. Montmorillonite clay, magnesium aluminum silicate (MAS), was used in this study. The results showed that chitosan-MAS microparticles with different chitosan MWs prepared by spray drying had similar micromeritic properties but displayed different nanocomposite types. The microparticles possibly possessed plastic deformation under the compression pressures to form matrix tablets. The tablets had greater hardness with increasing chitosan MW. Increasing the chitosan MW caused greater swelling of the tablets in acidic medium but reduced swelling in neutral medium. Chitosan-MAS tablets presented sustained-release patterns in both acidic and neutral media, and the drug release of the tablets in neutral medium decreased when using chitosan of higher MW. Furthermore, the introduction of up to 5%w/w magnesium stearate provided the tablets with lower hardness, higher friability, and lower drug release in acidic medium. These findings suggest that chitosan MW and lubricant content are important factors in the formulation of chitosan-MAS tablets and these tablets present good potential for oral sustained-release drug delivery.

Carboxylic acid terminated, solution exfoliated graphite by organic acylation and its application in drug delivery

Graphite nanosheets are considered as a promising material for a range of applications from flexible electronics to functional nanodevices such as biosensors, intelligent coatings and drug delivery. Chemical functionalization of graphite nanosheets with organic/inorganic materials offers an alternative approach to control the electronic properties of graphene, which is a zero band gap semiconductor in pristine form. In this paper, we report the aromatic electrophilic substitution of solution exfoliated graphite nanosheets (SEGn). The highly conjugated π-electronic system of graphite nanosheets enable it to have an amphiphilic characteristic in aromatic substitution reactions. The substitution was achieved through Friedel–Crafts (FC) acylation reaction under mild conditions using succinic anhydride as acylating agent and anhydrous aluminum chloride as Lewis acid. Such reaction renders towards the carboxylic acid terminated graphite nanosheets (SEGn–FC) that usually requires harsh reaction conditions. The product thus obtained was characterized using various spectroscopic and microscopic techniques. Highly stable water-dispersed sodium salt of carboxylic acid terminated graphite nanosheets (SEGn–FC-Na) was also prepared. A comparative sheet-resistance measurements of SEGn, SEGn–FC and SEGn–FC-Na were also done. Finally, the anticancer drug doxorubicin (DOX) was loaded on water dispersible SEGn–FC-Na with a loading capacity of 0.266 mg mg−1 of SEGn–FC-Na and the release of DOX from this water-soluble DOX-loaded SEGn–FC-Na at two different temperatures was found to be strongly pH dependent. Selective carboxylic acid terminated solution exfoliated graphite nanosheets were achieved through Friedel–Crafts acylation reaction and dispersed in water by making Na-salt of the same. Anticancer drug doxorubicin was successfully loaded onto this highly water dispersible Na-salt and the drug release was found to be pH dependant. The low cost and efficient drug release make it a potential carrier for targeted drug delivery.

Controlled-release drug carriers based mesoporous silica spheres with hierarchical hollow/nano structure

Mesoporous silica spheres with hierarchical hollow/nano structure (MSSH-H/N) have been successfully prepared by a template-guided approach, in which cetyltrimethyl ammonium bromide (CTAB) and polystyrene (PS) emulsion was used as the template of mesopores and hollow core, respectively. A consecutive template mechanism and the formation of the hierarchical hollow/nano structure were proposed on basis of the combined characterizations including transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction patterns (XRD) and nitrogen sorption analysis, which showed that the hierarchical structure is composed of mesoporous hollow SiO2 spheres and discrete mesoporous SiO2 nanoparticles coating on the shell. Ibuprofen (IBU) was chosen as a drug model in delivery and release experiments, and these MSSH-H/N samples exhibited higher drug loading capacity, desired low initial IBU release rate and typical two-phase drug release behavior compared with conventional single-structure (single-shelled) hollow mesoporous silica spheres due to their unique hierarchical hollow/nano structure.

Coatings of Eudragit® RL and L-55 Blends: Investigations on the Drug Release Mechanism.

In a previous study, generally lower drug release rates from RL:L55 blend coated pellets in neutral/basic release media than in acidic release media were reported. The aim of this study was to obtain information on the drug release mechanism of solid dosage forms coated with blends of Eudragit® RL (RL) and Eudragit® L-55 (L55). Swelling experiments with free films were analyzed spectroscopically and gravimetrically to identify the physicochemical cause for this release behavior. With Raman spectroscopy, the swelling of copolymer films could be monitored. IR spectroscopic investigations on RL:L55 blends immersed in media at pH 6.8 confirmed the formation of interpolyelectrolyte complexes (IPECs) that were not detectable after swelling in hydrochloric acid pH 1.2. Further investigations revealed that these IPECs decreased the extent of ion exchange between the quaternary ammonium groups of RL and the swelling media. This is presumably the reason for the previously reported decreased drug permeability of RL:L55 coatings in neutral/basic media as ion exchange is the determining factor in drug release from RL coated dosage forms. Gravimetric erosion studies confirmed that L55 was not leached out of the film blends during swelling in phosphate buffer pH 6.8. In contrast to all other investigated films, the 4:1 (RL:L55) blend showed an extensive swelling within 24 h at pH 6.8 which explains the reported sigmoidal release behavior of 4:1 blend coated pellets. These results help to understand the release behavior of RL:L55 blend coated solid dosage forms.