Ultrasensitive separation of methylprednisolone acetate using a photoresponsive molecularly imprinted polymer incorporated polyester dendrimer based on magnetic nanoparticles.

We developed an approach for the use of polyester dendrimer during the imprinting process to raise the number of recognized sites in the polymer matrix and improve its identification ability. Photoresponsive molecularly imprinted polymers were synthesized on modified magnetic nanoparticles involving polyester dendrimer which uses the reactivity between allyl glycidyl ether and acrylic acid for the high-yielding assembly by surface polymerization. The photoresponsive molecularly imprinted polymers were constructed using methylprednisoloneacetate as the template, water-soluble azobenzene involving 5-[(4, 3-(methacryloyloxy) phenyl) diazenyl] dihydroxy aniline as the novel functional monomer, and ethylene glycol dimethacrylate as the cross-linker. Through the evaluation of a series of features of spectroscopic and nano-structural, this sorbent showed excellent selective adsorption, recognition for the template, and provided a highly selective and sensitive strategy for determining the methylprednisoloneacetate in real and pharmaceutical samples. In addition, this sorbent according to good photo-responsive features and specific affinity to methylprednisoloneacetate with high recognition ability, represented higher binding capacity, a more extensive specific area, and faster mass transfer rate than its corresponding surface molecularly imprinted polymer.

Formulation Optimization and Assessment of Dexamethasone Orally Disintegrating Tablets Using Box-Behnken Design.

The aim of this study was to prepare orally disintegrating tablets (ODTs) containing dexamethasone (DEX) by direct compression method with sufficient hardness and rapid disintegration time. In order to save time, money, and human resources in designing and improvement of formulation, the statistical software Design Expert is used. Box-Behnken response surface methodology was applied to evaluate and optimize the effects of concentrations of three excipients, Kollidon CL-SF (X1), Pearlitol SD200 (X2), and Prosolv SMCC (X3) as independent factors on four responses: percentage of drug released after 5 min, disintegrating time, hardness, and friability. Thirteen formulations offered by the Box-Behnken design were prepared by direct compression method and ultimate weight of 200 mg, while the amount of DEX was 4 mg. All formulations were characterized for parameters such as diameter, hardness, weight, thickness, friability, and disintegration time. Following the statistical results, the effects of independent variables on responses were evaluated and the optimum formulation regarding acceptable responses consisted of 15% Kollidon, 39.66% Pearlitol, and 7.5% Prosolv which showed 95.28% release of the drug after 5 min, disintegrating time of 30 sec, 6.1 kg hardness, and 0.12% of friability with an acceptable taste as the optimized formulation.

Providing hyper-branched dendrimer conjugated with ß-cyclodextrin based on magnetic nanoparticles for the separation of methylprednisolone acetate.

This study introduced a developed approach for dendritic ß-cyclodextrin (ß-CD) in order to obtain high sorption capacity. Synthetic strategy exploits the reactivity between acrylic acid and allyl glycidyl ether for high-yielding assembly via grafting on to the magnetic nanoparticles that are modified using 3-mercaptopropyltrimethoxysilane for various building branches and host-guest molecules of ß-CD. The methodology has been applied for the preparation of a series of ß-CD conjugated magnetic nanoparticles with dendrimers as a nano-sorbent for the extraction of methylprednisolone acetate. This study allowed us to probe (i) the effects of the dendric-cyclodextrin architecture on the affinity of sorption capacity, (ii) the drug influence between the cyclodextrin core and the polyester dendrimer, and (iii) the result of sorbent formation for using the anti-inflammatory drug as a target guest into the ring of ß-CD on biological extraction. It was found that the adsorption behavior could be fitted by the Langmuir adsorption isotherm model. The adsorption capacity of MPA is found to be 12.4 mg g-1 and indicated the homogeneous sites onto polymer grafted magnetite nano-sorbent surface. Our results confirm the high capability of this type of dendrimer-ß-CD for drug extraction in biological fluids and pharmaceutical samples. This nano-sorbent assists the magnetic solid phase extraction technique represented in the high extraction yield (up to 97%) for methylprednisolone acetate in biological human fluids and pharmaceutical samples. Moreover, the achieved polymeric nano-sorbent of the reaction combination was facilitated by a magnetic field and reusability was performed without any notable loss in the sorbent activity.

Single Layer Extended Release Two-in-One Guaifenesin Matrix Tablet: Formulation Method, Optimization, Release Kinetics Evaluation and Its Comparison with Mucinex® Using Box-Behnken Design.

Guaifenesin, a highly water-soluble active (50 mg/mL), classified as a BCS class I drug. Owing to its poor flowability and compressibility, formulating tablets especially high-dose one, may be a challenge. Direct compression may not be feasible. Bilayer tablet technology applied to Mucinex®, endures challenges to deliver a robust formulation. To overcome challenges involved in bilayer-tablet manufacturing and powder compressibility, an optimized single layer tablet prepared by a binary mixture (Two-in-one), mimicking the dual drug release character of Mucinex® was purposed. A 3-factor, 3-level Box-Behnken design was applied to optimize seven considered dependent variables (Release "%" in 1, 2, 4, 6, 8, 10 and 12 h) regarding different levels of independent one (X1: Cetyl alcohol, X2: Starch 1500®, X3: HPMC K100M amounts). Two granule portions were prepared using melt and wet granulations, blended together prior to compression. An optimum formulation was obtained (X1: 37.10, X2: 2, X3: 42.49 mg). Desirability function was 0.616. F2 and f1 between release profiles of Mucinex® and the optimum formulation were 74 and 3, respectively. An n-value of about 0.5 for both optimum and Mucinex® formulations showed diffusion (Fickian) control mechanism. However, HPMC K100M rise in 70 mg accompanied cetyl alcohol rise in 60 mg led to first order kinetic (n = 0.6962). The K values of 1.56 represented an identical burst drug releases. Cetyl alcohol and starch 1500® modulated guaifenesin release from HPMC K100M matrices, while due to their binding properties, improved its poor flowability and compressibility, too.

Water-compatible molecularly imprinted polymer as a sorbent for the selective extraction and purification of adefovir from human serum and urine.

A molecularly imprinted polymer has been synthesized to specifically extract adefovir, an antiviral drug, from serum and urine by dispersive solid-phase extraction before high-performance liquid chromatography with UV analysis. The imprinted polymers were prepared by bulk polymerization by a noncovalent imprinting method that involved the use of adefovir (template molecule) and functional monomer (methacrylic acid) complex prior to polymerization, ethylene glycol dimethacrylate as cross-linker, and chloroform as porogen. Molecular recognition properties, binding capacity, and selectivity of the molecularly imprinted polymers were evaluated and the results show that the obtained polymers have high specific retention and enrichment for adefovir in aqueous medium. The new imprinted polymer was utilized as a molecular sorbent for the separation of adefovir from human serum and urine. The serum and urine extraction of adefovir by the molecularly imprinted polymer followed by high-performance liquid chromatography showed a linear calibration curve in the range of 20-100 µg/L with excellent precisions (2.5 and 2.8% for 50 µg/L), respectively. The limit of detection and limit of quantization were determined in serum (7.62 and 15.1 µg/L), and urine (5.45 and 16 µg/L). The recoveries for serum and urine samples were found to be 88.2-93.5 and 84.3-90.2%, respectively.

Molecularly imprinted nanoparticles prepared by miniemulsion polymerization as a sorbent for selective extraction and purification of efavirenz from human serum and urine.

A molecularly imprinted polymer (MIP) has been synthesized in order to specifically extract efavirenz from serum and urine by dispersive solid-phase extraction following by HPLC-UV analysis. The imprinted nanoparticles were prepared by miniemulsion polymerization method using efavirenz as template molecule and methacrylic acid as functional monomer. Molecular recognition properties, binding capacity and selectivity of the MIPs were evaluated and the results revealed that the obtained MIPs had high specific retention for efavirenz in aqueous medium. The MIP was used as a molecular sorbent for the separation of efavirenz from human serum and urine. The extraction of efavirenz by MIP coupled with HPLC analysis showed a linear calibration curve in the range of 50-300 µg/L with exellent precisions (3.66% and 4.6% for 100 and 300 µg/L respectively). The limit of detection (LOD) and limit of quantification (LOQ) were determind in serum (17.3 and 57.5 µg/L) and urine (10.6 and 36.2 µg/L). The maximum recoveries for serum and urine samples were found to be 95.2% and 92.7% respectively. Due to the high precision and accuracy, this method may be the UV-HPLC choice with MIP extraction for bioequivalence analysis of efavirenz in serum and urine.

Selective extraction of clonazepam from human plasma and urine samples by molecularly imprinted polymeric beads.

A molecularly imprinted polymer (MIP) based on free-radical polymerization was prepared with 1-(N,N-biscarboxymethyl)amino-3-allylglycerol and N,N-dimethylacrylamide as functional monomers, N,N-methylene diacrylamide as the cross-linker, copper ion-clonazepam as the template and 2,2-azobis(2-methylbutyronitrile) as the initiator. The imprinted polymer was characterized by Fourier transform infrared spectroscopy, elemental analysis, thermo-gravimetric analysis, and SEM. The MIP of agglomerated microparticles with multipores was used for SPE. The imprinted polymer sorbent was selective for clonazepam. The optimum pH and sorption capacity were 5 and 0.18 mg/g at 20C, respectively. The profile of the drug uptake by the sorbent reflects good accessibility of the active sites in the imprinted polymer sorbent. The MIP-SPE was the most feasible technique for the extraction of clonazepam with a high recovery from human plasma and urine samples.

Selective extraction of lamivudine in human serum and urine using molecularly imprinted polymer technique.

In this work, a novel technique is described for determination of lamivudine in biological fluids by molecularly imprinted polymers (MIPs) as the sample clean-up method joint with high performance liquid chromatography (HPLC). MIPs were prepared using methacrylic acid as functional monomer, ethylene glycol dimethacrylate as crosslinker, acetonitrile and tetrahydrofuran as porogen and lamivudine as the template molecule. The new imprinted polymer was used as a molecular sorbent for the separation of lamivudine from human serum and urine. Molecular recognition properties, binding capacity and selectivity of the MIPs were evaluated and the results showed that the obtained MIPs have a high affinity for lamivudine in aqueous medium. HPLC analyses showed that the extraction of lamivudine from serum and urine by MIPs had a linear calibration curve in the range of 60-700µg/L with excellent precisions of 2.73% for serum and 2.60% for urine. The limit of detection and quantization of lamivudine was 19.34 and 58.6µg/L in serum and 7.95 and 24.05µg/L in urine respectively. MIP extraction provided about 10 fold LOQ improvement in serum and 5 fold LOQ improvement in urine samples. The recoveries of lamivudine in serum and urine samples were found to be 84.2-93.5% and 82.5-90.8% respectively. Due to the high precision and accuracy, this method may be the UV-HPLC choice with MIP extraction for bioequivalence analysis of lamivudine in serum and urine.

Solid carriers for improved solubility of glipizide in osmotically controlled oral drug delivery system.

The purpose of this study was to increase the solubility of glipizide (gli) by solid dispersions SDs technique with polyvinylpyrrolidone (PVP) in aqueous media. The gli-PVP solid dispersion systems was prepared by physical mixing or spray drying method, and characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) analysis, Fourier transformation-infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The elementary osmotic pumps (EOPs) were prepared with gli-PVP complex and the effect of the PVP percentages on the enhancing of gli dissolution rate was studied. The influences of various parameters e.g., drug- PVP ratio, level of solubility modifier, coating weight gain and diameter of drug releasing orifice on drug release profiles were also investigated. The solubility and dissolution rates of gli were significantly increased by solid dispersion using spray dried method as well as their physical mixture. The obtained results indicated that gli-PVP solid dispersion system has suitable solubility behavior in EOP tablets.