Ionic Liquid Cross-Linked High-Absorbent Polymer Hydrogels: Kinetics of Swelling and Dye Adsorption.

The use of polymer gels for the removal of toxic chemicals from wastewater is an important area in terms of both academic and industrial research. This work presents a simple approach to the fabrication of chemically cross-linked cationic hydrogel adsorbents using designed ionic liquid-based cross-linkers and their successful use in the removal of organic dyes. Two different ionic liquid cross-linkers, [VIm-4VBC][Cl] (ILA)/[DMAEMA-4VBC][Cl] (ILB), are synthesized by the simple nucleophilic substitution reaction of 4-vinylbenzyl chloride (4VBC) separately with 1-vinylimidazole (VIm) and 2-(dimethylamino)ethyl methacrylate (DMAEMA). Cross-linked poly(acrylamide) (CPAam) and poly(2-hydroxyethyl methacrylate) (CPHEMA) hydrogels are then prepared from the corresponding monomers and as-synthesized cross-linkers (ILA and ILB) by free radical polymerization in the presence of a redox initiator combining ammonium persulfate (APS) and N,N,N',N'-tetramethylethylenediamine (TEMED). The dried CPAam and CPHEMA xerogels exhibit macroporous morphology and high thermal stability. The hydrogel samples exhibit high swelling behavior, and the diffusion of water molecules into the hydrogels follows pseudo-Fickian kinetics. The cationic cross-linking sites in the hydrogel networks allow preferable binding with anionic dyes, and these dye uptake capacities are determined using different model anionic dyes via UV-vis spectroscopy. The dye adsorption onto these hydrogels follows a pseudo-second-order kinetic model. The adsorption mechanism is also analyzed by employing intraparticle diffusion and Boyd kinetic models. The relationship between the maximum equilibrium adsorption capacity (qm) of the hydrogels for eosin B (EB) dye and the equilibrium EB concentration can be better described by Langmuir and Freundlich isotherm models, and the estimated qm using the Langmuir isotherm can reach more than 100 mg g-1. The cross-linked hydrogels can be easily regenerated and have a recycling efficiency of >80% for up to three consecutive dye adsorption-desorption cycles, which is promising for their use in wastewater treatment.

Chemical Tuning of Zwitterionic Ionic Liquids for Variable Thermophysical Behaviours, Nanostructured Aggregates and Dual-Stimuli Responsiveness.

The design and synthesis of a series of zwitterionic ionic liquids (ZILs) to understand the structure-property relationship towards an increase of the thermal stability, a variation of the glass transition temperature, the shape-tuning of nanostructured aggregates and the tuning of the stimuli responsiveness are demonstrated. The substitution reaction of imidazole with various aliphatic and aromatic bromides followed by the reaction of the corresponding substituted imidazoles with bromoalkyl carboxylic acids of varying spacer length produces the ZILs. In aqueous solution, a ZIL molecule either exist in its ionic liquid (substituted imidazolium bromide) form or its zwitterionic (substituted imidazolium alkyl carboxylate) form with an isoelectric point (pI) depending on the pH value of the solution. Upon changing the pH to near or above the pI, the aqueous ZIL solution undergoes transition from a transparent to a turbid phase due to the formation of insoluble hierarchical nanostructured aggregates of various morphologies, such as spheres, tripods, tetrapods, fern-like, flower-like, dendrites etc. depending on the pH of the solution and the nature of the alkyl/vinyl/aryl substituents. Upon heating the solution a phase transition occurs from turbid to transparent, exhibiting a distinct reversible upper critical solution temperature (UCST)-type cloud point (Tcp ). It is observed that the cloud point varies with the nature of the substituent, an increase of the concentration of the ZIL as well as with changes of the pH of the solution.

Poly[oligo(2-ethyl-2-oxazoline)acrylate]-Based Poly(ionic liquid) Random Copolymers with Coexistent and Tunable Lower Critical Solution Temperature- and Upper Critical Solution Temperature-Type Phase Transitions.

The synthesis of a series of dual thermosensitive nonionic-ionic random copolymers with varying compositions by reversible addition-fragmentation chain transfer polymerization is described. These copolymers contain oligo(2-ethyl-2-oxazoline)acrylate (OEtOxA) and either triphenyl-4-vinylbenzylphosphonium chloride ([VBTP][Cl]) or 3- n-butyl-1-vinylimidazolium bromide ([VBuIm][Br]) ionic liquid (IL) units. The copolymers having low content of ionic poly(ionic liquid) (PIL) (P[VBTP][Cl]/P[VBuIm][Br]) segments show only lower critical solution temperature (LCST)-type phase transition with almost linear increase of their cloud points with increasing percentage of ionic PIL segments. Furthermore, LCST-type cloud points ( TcLs) are found very sensitive and tunable with respect to the nature and concentration of halide ions (X- = Cl-, Br-, and I-) and copolymer compositions. However, copolymers with high content of ionic PIL segments show both LCST-type followed by upper critical solution temperature (UCST)-type phase transitions in the presence of halide ions. Dual LCST- and UCST-type phase behaviors are prominent and repeatable for many heating/cooling cycles. Both types of cloud points are found to be sensitive to copolymer compositions, concentration, and nature and concentration of the halide ions. The phase behaviors of both types of copolymers with a very high ionic content (>90%) are exactly similar to that of P[VBTP][Cl] or P[VBuIm][Br] homopolymers showing only UCST-type phase transition in the presence of halide ions. The inherent biocompatibility of the P(OEtOxA) segment along with the interesting dual thermoresponsiveness makes these copolymers highly suitable candidates for biomedical applications including drug delivery.

Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection.

The purpose of this study was two-fold: (1) to formulate γ-tocotrienol (GT3) in a nanoemulsion formulation as a prophylactic orally administered radioprotective agent; and (2) to optimize the storage conditions to preserve the structural integrity of both the formulation and the compound. γ-tocotrienol was incorporated into a nanoemulsion and lyophilized with lactose. Ultra performance liquid chromatography-mass spectroscopy (UPLC-MS) was used to monitor the chemical stability of GT3 over time, the particle size and ζ potential, and scanning electron microscopy (SEM) were used to study the physical stability of the nanoemulsion. Radioprotective and toxicity studies were performed in mice. The liquid formulation exhibited GT3 degradation at all storage temperatures. Lyophilization, in the presence of lactose, significantly reduced GT3 degradation. Both the liquid and lyophilized nanoemulsions had stable particle size and ζ potential when stored at 4 °C. Toxicity studies of the nanoemulsion resulted in no observable toxicity in mice at an oral dose of 600 mg/kg GT3. The nano-formulated GT3 (300 mg/kg) demonstrated enhanced survival efficacy compared to GT3 alone (200 and 400 mg/kg) in CD2F1 mice exposed to total body gamma radiation. The optimal long-term storage of formulated GT3 is as a powder at -20 °C to preserve drug and formulation integrity. Formulation of GT3 as a nanoemulsion for oral delivery as a prophylactic radioprotectant shows promise and warrants further investigation.

Imidazolium-based ionic liquids with different fatty acid anions: phase behavior, electronic structure and ionic conductivity investigation.

The thermal phase behaviors of a series of newly designed 1-alkyl-3-methylimidazolium ionic liquids (ILs) of different chain length fatty acid carboxylate anions are investigated. The length of the alkyl chain of the carboxylate anion in IL influences the phase transition temperature of their crystalline solid phase and the mesophase stability. When the palmitate anion of the IL is replaced with palmitoyl ascorbate and palmitoyl-L-tryptophanate anions, its melting temperature decreases and eventually vanishes. The influence of structural modulation of ILs on their ionic conductivities is also studied. The interaction between the 1-alkyl-3-methylimidazolium cation and the fatty acid carboxylate anion is established by using ab initio based DFT calculations. The associated energies for single ion pair formation of these ILs are computed and are successfully correlated with the experimental findings, which finally leads to the most reasonable arrangement of the IL molecules in different phases.

Development and in vitro evaluation of a nanoemulsion for transcutaneous delivery.

OBJECTIVE: The purpose of this study is to develop a nanoemulsion formulation for its use as a transcutaneous vaccine delivery system. MATERIALS AND METHODS: With bovine albumin-fluorescein isothiocyanate conjugate (FITC-BSA) as a vaccine model, formulations were selected with the construction of pseudo-ternary phase diagrams and a short-term stability study. The size of the emulsion droplets was furthered optimized with high-pressure homogenization. The optimized formulation was evaluated for its skin permeation efficiency. In vitro skin permeation studies were conducted with shaved BALB/c mice skin samples with a Franz diffusion cell system. Different drug concentrations were compared, and the effect of the nanoemulsion excipients on the permeation of the FITC-BSA was also studied. RESULTS: The optimum homogenization regime was determined to be five passes at 20 000 psi, with no evidence of protein degradation during processing. With these conditions, the particle diameter was 85.2 nm ± 15.5 nm with a polydispersity index of 0.186 ± 0.026 and viscosity of 14.6 cP ± 1.2 cP. The optimized formulation proved stable for 1 year at 4 °C. In vitro skin diffusion studies show that the optimized formulation improves the permeation of FITC-BSA through skin with an enhancement ratio of 4.2 compared to a neat control solution. Finally, a comparison of the skin permeation of the nanoemulsion versus only the surfactant excipients resulted in a steady state flux of 23.44 µg/cm(2)/h for the nanoemulsion as opposed to 6.10 µg/cm(2)/h for the emulsifiers. CONCLUSION: A novel nanoemulsion with optimized physical characteristics and superior skin permeation compared to control solution was manufactured. The formulation proposed in this study has the flexibility for the incorporation of a variety of active ingredients and warrants further development as a transcutaneous vaccine delivery vehicle.

Physicochemical and Microbiological Stability of Compounded Clonidine Hydrochloride Oral Liquid Dosage Forms in PCCA Base, SuspendIt®.

Clonidine Hydrochloride is a centrally acting alpha-agonist hypotensive agent available as tablets for oral administration in three dosage strengths: 0.1 mg, 0.2 mg and 0.3 mg. A review of the therapeutic uses of clonidine hydrochloride reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of clonidine hydrochloride currently exists. An extemporaneously compounded suspension from pure drug powder would provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded clonidine hydrochloride suspensions in the PCCA Base, SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two clonidine hydrochloride concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating high-performance liquid chromatographic assay for the determination of the chemical stability of clonidine hydrochloride in PCCA SuspendIt was developed and validated. Suspensions of clonidine hydrochloride were prepared in PCCA SuspendIt at 20-mcg/mL and 100-mcg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Given the potent nature of the drug, a 2% triturate of clonidine hydrochloride in microcrystalline cellulose was used to prepare the samples. Samples were stored in amber plastic prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and on the following time points (days): 7, 14, 28, 42, 63, 91, 119 and 182. Physical data such as pH, viscosity and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. Using this criterion, no significant degradation of the clonidine hydrochloride was observed over the 182-day test period for either concentration under refrigerated conditions. Drug concentrations were at, or above 94.6% of initial values. However, at room temperature the concentration of the 20-mcg/mL samples dropped below 90% after 119 days. No microbial growth was observed. pH values remained fairly constant. The viscosity of the suspensions allowed easy re-dispersal of the drug particles upon shaking. This study demonstrates that clonidine hydrochloride is physically, chemically, and microbiologically stable in PCCA SuspendIt for 182 days in the refrigerator and for 119 days at room temperature at both concentrations studied, thus providing a viable, compounded alternative for clonidine hydrochloride in a liquid dosage form, with an extended BUD to meet patient needs.

An interplay of cooperativity between cation⋠⋠⋠π, anion⋠⋠⋠π and C-H⋠⋠⋠anion interactions.

Mixed cation (Li(+), Na(+) and K(+)) and anion (F(-), Cl(-), Br(-)) complexes of the aromatic π-surfaces (top and bottom) are studied by using dispersion-corrected density functional theory. The selectivity of the aromatic surface to interact with a cation or an anion can be tuned and even reversed by the electron-donating/electron-accepting nature of the side groups. The presence of a methyl group in the -OCH3, -SCH3, -OC2H5 in the side groups of the aromatic ring leads to further cooperative stabilization of the otherwise unstable/weakly stable anion⋅⋅⋅π complexes by bending of the side groups towards the anion to facilitate C-H⋅⋅⋅anion interactions. The cooperativity among the interactions is found to be as large as 100 kcal mol(-1) quantified by dissection of the three individual forces from the total interaction energy. The crystal structures of the fluoride binding tripodal and hexapodal ligands provide experimental evidence for such cooperative interactions.

Amino-acid-based zwitterionic polymer and its Cu(II)-induced aggregation into nanostructures: a template for CuS and CuO nanoparticles.

A convenient and water-based approach is described for the synthesis of an l-lysine-based zwitterionic polymer, poly(ε-l-lysinyl acrylamide) (PLAM), without using protecting group chemistry, chromatographic purifications, and organic solvents as the reaction media. PLAM contains both amine and carboxylic acid groups in each repeating unit, which can either be protonated or deprotonated just by altering the pH of the solution to obtain overall positive or negative charge. PLAM is tested for its applicability as a zwitterionic polymeric buffer in water. Cu(II) ion-induced aggregation of PLAM as a function of solution pH is studied. Spherical nanogel aggregates are formed at pH 9.5 due to aggregation of PLAM through its complexation with Cu(II) ion. Spherical aggregates appear to dissociate via breaking of the complexation at a pH < 5.5 resulting in molecular dissolution of PLAM. This aggregation process is pH reversible. The Cu(II)-PLAM aggregates are used as a template for fabrication of CuO and CuS nanoparticles.

Inhibition of hepatitis C virus replication by intracellular delivery of multiple siRNAs by nanosomes.

Sustained antiviral responses of chronic hepatitis C virus (HCV) infection have improved recently by the use of direct-acting antiviral agents along with interferon (IFN)-α and ribavirin. However, the emergence of drug-resistant variants is expected to be a major problem. We describe here a novel combinatorial small interfering RNA (siRNA) nanosome-based antiviral approach to clear HCV infection. Multiple siRNAs targeted to the highly conserved 5'-untranslated region (UTR) of the HCV genome were synthesized and encapsulated into lipid nanoparticles called nanosomes. We show that siRNA can be repeatedly delivered to 100% of cells in culture using nanosomes without toxicity. Six siRNAs dramatically reduced HCV replication in both the replicon and infectious cell culture model. Repeated treatments with two siRNAs were better than a single siRNA treatment in minimizing the development of an escape mutant, resulting in rapid inhibition of viral replication. Systemic administration of combinatorial siRNA-nanosomes is well tolerated in BALB/c mice without liver injury or histological toxicity. As a proof-of-principle, we showed that systemic injections of siRNA nanosomes significantly reduced HCV replication in a liver tumor-xenotransplant mouse model of HCV. Our results indicate that systemic delivery of combinatorial siRNA nanosomes can be used to minimize the development of escape mutants and inhibition of HCV infection.

Stimuli-Responsive Triblock Terpolymer Conversion into Multi-Stimuli-Responsive Micelles with Dynamic Covalent Bonds for Drug Delivery through a Quick and Controllable Post-Polymerization Reaction.

Stimuli-responsive copolymers are of great interest for targeted drug delivery. This study reports on a controllable post-polymerization quaternization with 2-bromomethyl-4-fluorophenylboronic acid of the poly(4-vinyl pyridine) (P4VP) block of a common poly(styrene)-b-poly(4-vinyl pyridine)-b-poly(ethylene oxide) (SVE) triblock terpolymer in order to achieve a selective responsivity to various diols. For this purpose, a reproducible method was established for P4VP block quaternization at a defined ratio, confirming the reaction yield by 11B, 1H NMR. Then, a reproducible self-assembly protocol is designed for preparing stable micelles from functionalized stimuli-responsive triblock terpolymers, which are characterized by light scattering and by cryogenic transmission electron microscopy. In addition, UV-Vis spectroscopy is used to monitor the boron-ester bonding and hydrolysis with alizarin as a model drug and to study encapsulation and release of this drug, induced by sensing with three geminal diols: fructose, galactose and ascorbic acid. The obtained results show that only the latter, with the vicinal diol group on sp2-hybridized carbons, was efficient for alizarin release. Therefore, the post-polymerization method for triblock terpolymer functionalization presented in this study allows for preparation of specific stimuli-responsive systems with a high potential for targeted drug delivery, especially for cancer treatment.

Physiochemical and Microbiological Stability of Azathioprine Suspensions in PCCA Base, SuspendIt.

Azathioprine is used to treat the symptoms of rheumatoid arthritis and for the prevention of transplant rejection. A review of the therapeutic uses of Azathioprine reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of Azathioprine currently exists. Azathioprine is commercially available only as a 50-mg tablet. An extemporaneously compounded suspension from pure drug powder would provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded Azathioprine suspensions in the PCCA Base, SuspendIt. This base is a sugar-free, paraben free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two Azathioprine concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating high-performance liquid chromatographic assay for the determination of the chemical stability of Azathioprine in PCCA SuspendIt was developed and validated. Suspensions of Azathioprine were prepared in PCCA SuspendIt at 10-mg/mL and 50-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in amber plastic prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and on the following time points (days): 7, 14, 28, 49, 63, 90, 119, and 182. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that Azathioprine concentrations did not go below 96.8% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. The pH values remained constant. The viscosity of the suspensions allowed easy re-dispersal of the drug particles upon shaking. This study demonstrates that Azathioprine is physically, chemically, and microbiologically stable in PCCA SuspendIt for 182 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for Azathioprine in a liquid dosage form, with an extended beyond-use date to meet patient needs.

Physicochemical and Microbiological Stability of Amitriptyline Hydrochloride Oral Liquid Dosage Forms in PCCA Base, SuspendIt.

Amitriptyline hydrochloride is indicated for the relief of symptoms of depression. A review of the therapeutic uses of amitriptyline hydrochloride reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of amitriptyline currently exists. Amitriptyline hydrochloride is commercially available only as 10-mg, 25-mg, 50-mg, 75-mg, 100-mg, and 150-mg tablets. An extemporaneously compounded suspension from pure drug powder would provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded amitriptyline hydrochloride suspensions in PCCA Base, SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two amitriptyline hydrochloride concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability- indicating high-performance liquid chromatographic assay for the determination of the chemical stability of amitriptyline hydrochloride in PCCA SuspendIt was developed and validated. Suspensions of amitriptyline hydro- chloride were prepared in PCCA SuspendIt at 1-mg/mL and 5-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in amber plastic prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and on the following time points (days): 7, 14, 28, 49, 63, 91, 119, and 185. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that amitriptyline hydrochloride concentrations did not go below 99.8% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. The pH values remained constant. The viscosity of the suspensions allowed easy re-dispersal of the drug particles upon shaking. This study demonstrates that amitriptyline hydrochloride is physically, chemically, and microbiologically stable in PCCA SuspendIt for 185 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for amitriptyline hydrochloride in a liquid dosage form, with an extended beyond-use date to meet patient needs.

Physicochemical and Microbiological Stability of Compounded Metronidazole Suspensions in PCCA SuspendIt.

Metronidazole is indicated for the treatment of trichomoniasis, amebiasis, and anaerobic bacterial infections. The dosage regimen of metronidazole needs to be individualized in the treatment of trichomoniasis, in patients with hepatic impairment, and in pediatric as well as geriatric patients. A review of the therapeutic uses of metronidazole reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of metronidazole currently exists. Metronidazole is commercially available only as 250-mg and 500-mg film-coated tablets. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded metronidazole suspensions in PCCA SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two metronidazole concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating ultra-performance liquid chromatographic assay for the determination of the chemical stability of metronidazole in PCCA SuspendIt was developed and validated. Suspensions of metronidazole were prepared in PCCA SuspendIt at 25-mg/mL and 50-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5ÆC and 25ÆC). Samples were assayed initially and on the following time points (days): 7, 14, 28, 42, 59, 90, 122, and 180. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was also tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that metronidazole concentrations did not go below 97% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. Viscosity and pH values also did not change significantly. This study demonstrates that metronidazole is physically, chemically, and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for metronidazole in a liquid dosage form, with an extended beyond-use-date to meet patient needs.

Physicochemical and Microbiological Stability of Extemporaneously Compounded Hydrocortisone Oral Suspensions in PCCA Base, SuspendIt.

Hydrocortisone is indicated in the treatment of primary or secondary adrenal insufficiency. The oral dosage regimen of hydrocortisone needs to be individualized in the treatment of congenital adrenal hyperplasia, especially in pediatric patients. A review of the therapeutic uses of hydrocortisone reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of hydrocortisone currently exists. Hydrocortisone is commercially available as 5-mg, 10-mg, and 20-mg tablets. An extemporaneously compounded suspension from pure drug powder would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded hydrocortisone suspensions in PCCA Base, SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two hydrocortisone concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating high-performance liquid chromatographic assay for the determination of the chemical stability of hydrocortisone in SuspendIt was developed and validated. Suspensions of hydrocortisone were prepared in SuspendIt at 1-mg/mL and 20-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially and on the following days: 7, 15, 28, 45, 60, 91, 120, and 185. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that hydrocortisone concentrations did not go below 94% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. Viscosity and pH values did not change significantly. This study demonstrates that hydrocortisone is physically, chemically, and microbiologically stable in SuspendIt for 185 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for hydrocortisone in a liquid dosage form, with an extended beyond-use date to meet patient needs.

Redox-active ionic-liquid-assisted one-step general method for preparing gold nanoparticle thin films: applications in refractive index sensing and catalysis.

We describe a general one-step facile method for depositing gold nanoparticle (GNP) thin films onto any type of substrates by the in situ reduction of AuCl(3) using a newly designed redox-active ionic liquid (IL), tetrabutylphosphonium citrate ([TBP][Ci]). Various substrates such as positively charged glass, negatively charged glass/quartz, neutral hydrophobic glass, polypropylene, polystyrene, plain paper, and cellophane paper are successfully coated with a thin film of GNPs. This IL ([TBP][Ci]) is prepared by the simple neutralization of tetrabutylphosphonium hydroxide with citric acid. We also demonstrate that the [TBP][Ci] ionic liquid can be successfully used to generate GNPs in an aqueous colloidal suspension in situ. The deposited GNP thin films on various surfaces are made up of mostly discrete spherical GNPs that are well distributed throughout the film, as confirmed by field-emission scanning electron microscopy. However, it seems that some GNPs are arranged to form arrays depending on the nature of surface. We also characterize these GNP thin films via UV-vis spectroscopy and X-ray diffractometry. The as-formed GNP thin films show excellent stability toward solvent washing. We demonstrate that the thin film of GNPs on a glass/quartz surface can be successfully used as a refractive index (RI) sensor for different polar and nonpolar organic solvents. The as-formed GNP thin films on different surfaces show excellent catalytic activity in the borohydride reduction of p-nitrophenol.

Ultrasound-induced in situ formation of coordination organogels from isobutyric acids and zinc oxide nanoparticles.

The discovery of ultrasound-induced in-situ formation of coordination organogels using various isobutyric acids (such as isobutyric acid or 2-methylisobutyric acid or 2-bromoisobutyric acid) and zinc oxide nanoparticles was described. FTIR and XRD results suggest that ultrasound irradiation triggers the quick dissolution of zinc oxide nanoparticles by isobutyric acids, resulting in the in-situ formation of zinc isobutyrate complexes that undergoes fast sonocrystallization into gel fibers. FESEM results clearly demonstrate the formation of well-defined networks of fibers with several micrometers in length, but the average diameter of the fiber ranges from 30 to 65 nm, depending upon the nature of the isobutyric acids used. A combination of single-crystal structure analysis and powder XRD result was used to envisage the molecular packing present in the gel state. This is probably a very rare case of ultrasound-induced organogelation where metal oxide NPs are used as the precursor.

Ascorbate-assisted growth of hierarchical ZnO nanostructures: sphere, spindle, and flower and their catalytic properties.

A simple solution-based method to prepare mainly flowerlike zinc oxide (ZnO) nanostructures using the ascorbate ion as a shape-directing/capping agent at relatively low temperature (ca. 30 and 60 degrees C) was described. However, we observed that different shapes of hierarchical ZnO nanostructures such as flowerlike, spindlelike, and spherical could be obtained with an increase in the synthesis temperature from 60 to 90 degrees C. The effects of other organic capping agents on the shape of hierarchical ZnO nanostructures were also studied. FTIR, FESEM, and XRD characterization were performed on the formed ZnO nanostructures to understand the role of ascorbate in the growth of flowerlike morphology. The nucleation and growth process can regulate by changing the metal precursor and ascorbate ion concentrations. We were able to identify intermediate nanostructures such as spherical/quasi-spherical and spindle that are very much on the pathway of formation of large, flowerlike ZnO nanostructures. Electron microscopy results indicated that these spherical/quasi-spherical ZnO nanoparticles might aggregate through oriented attachment to produce spindlelike and flowerlike nanostructures. On the basis of these results, a possible growth mechanism for the formation of flowerlike ZnO nanostructures was described. The optical properties of these differently shaped ZnO nanostructures were also described. The catalytic activities of the as-synthesized spherical and flowerlike ZnO nanostructures were tested in the Friedel-Crafts acylation reaction of anthracene with benzoyl chloride. The catalysis results indicated that the catalytic activity of flowerlike ZnO nanostructures is slightly higher than the spherical counterpart.

Optimization of DNA delivery by three classes of hybrid nanoparticle/DNA complexes.

Plasmid DNA encoding a luciferase reporter gene was complexed with each of six different hybrid nanoparticles (NPs) synthesized from mixtures of poly (D, L-lactide-co-glycolide acid) (PLGA 50:50) and the cationic lipids DOTAP (1, 2-Dioleoyl-3-Trimethyammonium-Propane) or DC-Chol {3beta-[N-(N', N'-Dimethylaminoethane)-carbamyl] Cholesterol}. Particles were 100-400 nm in diameter and the resulting complexes had DNA adsorbed on the surface (out), encapsulated (in), or DNA adsorbed and encapsulated (both). A luciferase reporter assay was used to quantify DNA expression in 293 cells for the uptake of six different NP/DNA complexes. Optimal DNA delivery occurred for 105 cells over a range of 500 ng - 10 mug of NPs containing 20-30 mug DNA per 1 mg of NPs. Uptake of DNA from NP/DNA complexes was found to be 500-600 times as efficient as unbound DNA. Regression analysis was performed and lines were drawn for DNA uptake over a four week interval. NP/DNA complexes with adsorbed NPs (out) showed a large initial uptake followed by a steep slope of DNA decline and large angle of declination; lines from uptake of adsorbed and encapsulated NPs (both) also exhibited a large initial uptake but was followed by a gradual slope of DNA decline and small angle of declination, indicating longer times of luciferase expression in 293 cells. NPs with encapsulated DNA only (in), gave an intermediate activity. The latter two effects were best seen with DOTAP-NPs while the former was best seen with DC-Chol-NPs. These results provide optimal conditions for using different hybrid NP/DNA complexes in vitro and in the future, will be tested in vivo.

Controlled release multiple layer coatings.

PURPOSE: In a fluid-bed coating machine, the coating solutions are normally sprayed using a manually controlled peristaltic pump. This study provides a process where two or more coating solutions can be sprayed consecutively using two or more syringe pumps controlled by a computer, to form multiple layers. In this process, the spraying parameters can be controlled easily from a computer. METHODS: Propranolol HCl was used as a model drug. Nine different drug-loaded controlled release coated beads were prepared by using a combination of ethylcellulose and/or chitosan solutions. The pulse-coated beads were prepared by changing the spray rate and/or volume of the polymer solutions. RESULTS: There was a fourfold increase (18 versus 75 minutes) in lag time when the same amount of ethylcellulose (4 g) was dissolved in 100 mL of ethanol instead of 160 mL. When the same amount of drug and ethylcellulose solution was applied on the acrylic coated beads as multiple layers coating, the lag time decreased to only 6 minutes. Similarly, the 50% drug release time also decreased significantly. CONCLUSION: An overall comparison of the dissolution profiles showed that drug release from these coated beads was changed significantly when the sequence of the drug and polymer layers was changed.