Muhammad Aslam Malana

The Release Behavior and Kinetic Evaluation of Tramadol HCl from Chemically Cross Linked Ter Polymeric Hydrogels

Background and the purpose of the studyHydrogels, being stimuli responsive are considered to be effective for targeted and sustained drug delivery. The main purpose for this work was to study the release behavior and kinetic evaluation of Tramadol HCl from chemically cross linked ter polymeric hydrogels.MethodsTer-polymers of methacrylate, vinyl acetate and acrylic acid cross linked with ethylene glycol dimethacrylate (EGDMA) were prepared by free radical polymerization. The drug release rates, dynamic swelling behavior and pH sensitivity of hydrogels ranging in composition from 1-10 mol% EGDMA were studied. Tramadol HCl was used as model drug substance. The release behavior was investigated at pH 8 where all formulations exhibited non-Fickian diffusion mechanism.Results and major conclusionAbsorbency was found to be more than 99% indicating good drug loading capability of these hydrogels towards the selected drug substance. Formulations designed with increasing amounts of EGDMA had a decreased equilibrium media content as well as media penetrating velocity and thus exhibited a slower drug release rate. Fitting of release data to different kinetic models indicate that the kinetic order shifts from the first to zero order as the concentration of drug was increased in the medium, showing gradual independency of drug release towards its concentration. Formulations with low drug content showed best fitness with Higuchi model whereas those with higher concentration of drug followed Hixson-Crowell model with better correlation values indicating that the drug release from these formulations depends more on change in surface area and diameter of tablets than that on concentration of the drug. Release exponent (n) derived from Korse-Meyer Peppas equation implied that the release of Tramadol HCl from these formulations was generally non-Fickian (n > 0.5 > 1) showing swelling controlled mechanism. The mechanical strength and controlled release capability of the systems indicate that these co-polymeric hydrogels have a great potential to be used as colon drug delivery device through oral administration.

Rheological characterization of novel physically crosslinked terpolymeric hydrogels at different temperatures

The main objective of this research work is to reveal the detailed and extensive rheological characterization of terpolymeric hydrogel formulations using a variety of monomers having different concentrations of acrylic acid and applying a range of temperatures. The hydrogels with the different concentrations of acrylic acid were prepared in the absence of air using three different monomers, by free radical polymerization, gradually increasing the temperature up to polymerization point, using ethyl alcohol as solvent. Different shear measurements were performed to study rheological properties, temperature dependence, and yield strength of acrylic acid pharmaceutical hydrogels. Various models were applied to analyze the rheological behavior of the gels. The acrylic acid pharmaceutical gels having physical cross links in the gel networks, exhibit remarkable temperature dependence especially with relatively higher concentration of acrylic acid at greater shear rate. Flow curves plotted at various temperatures indicate that these gels exhibit a reasonable pseudoplastic behavior. All these hydrogels require appropriate yield strength to break their network structures. The gel samples exhibit the best fit to the Modified Bingham model, which can explain the overall flow behavior of these topical gels. The rheological analysis indicates that these gels may be used as topical gels for targeted and controlled drug delivery at a specific site.

Synthesis, swelling behavior, and network parameters of novel chemically crosslinked poly (acrylamide-co-methacrylate-co-acrylic acid) hydrogels

The purpose of this study was to prepare a series of pH-sensitive hydrogels from acrylamide, methacrylate, and acrylic acid using different crosslinking agents. Hydrogels were prepared by free-radical copolymerization in alcoholic solution in the presence of a redox initiator, benzoyl peroxide, and crosslinkers, ethylene glycol dimethacrylate (EGDMA), and diethylene glycol dimethacrylate (DEGDMA). The effect of pH and the nature of the crosslinker on the swelling behavior of the copolymeric gels were investigated. Equilibrium swelling studies, in the pH range of 1–8, were performed to determine the average molecular weight between the crosslinks (Mc), the crosslink density (q), and the crosslink efficiency (f) using the Flory–Rehner equation. The average molecular weight between the crosslinks (Mc), 117–2394 for EGDMA and 81-14339 for DEHDMA, found to be increased with pH of the medium, whereas the crosslinking density (q) and crosslink efficiency (f) were decreased for EGDMA and DEGDMA as the pH of the medium was increased (q = 0.03–0.68 for EGDMA and 0.01–0.98 for DEGDMA, whereas f = 51–1056 for EGDMA and 9.9–1760 for DEGDMA). The diffusional exponent (n) values of the synthesized hydrogels were, in general, found to be non-Fickian (0.5 < n < 1). It was concluded that these copolymers demonstrated a sharp change in their media absorbancy and the network parameters with the change in the media pH. This behavior of the hydrogels suggest their strong candidature for being used as oral drug delivery systems targeting the colon part of gastrointestinal tract.

Formulation, Characterization, Study of Swelling Kinetics and Network Parameters of Poly (MA-co-VA-co-AA) Terpolymeric Hydrogels with Various Concentrations of Acrylic Acid

The ter-polymeric hydrogels of vinylacetate (VA), methacrylate (MA) and acrylicacid (AA) were prepared using ethyleneglycoldimethacrylate (EGDMA) as a cross linker and benzoylperoxide (BPO) as an initiator. The effect of acrylic acid concentration on various swelling parameters was studied at different pHs (1.0, 4.0, 5.5, 7.4 and 8.0). A promising relationship was found to exist between media penetration velocity and equilibrium media content of hydrogels at all pH values for various concentration of acrylic acid. The fastest dynamic swelling was observed for the highest concentration of acrylic acid (40 mol % of AA) at pH 8.0. In the kinetic study, during the first hours, a first order kinetics (Fick Model) was observed at pH higher than the value of pK a (4.75) of acrylic acid, the hydrogels exhibiting non-Fickian diffusion mechanism. Whereas, for the acidic media pH, a second order kinetics was observed (Schott Model). Network parameters strongly support the swelling out comes. The relaxations of the ter-polymeric chain were observed after swelling at pH 8.0 via SEM pictures. Thermo gravimetric analysis and differential scanning calorimetric analysis also agree with the above conclusions. Well controlled swelling behavior, network properties, SEM out comings and thermo-gravimetric analysis support the idea to use these hydrogels for targeted drug delivery in the colon part of the digestive tract.

Synthesis and characterization of stimuli-responsive hydrogel based on starch and methyl-3-aminocrotonate: swelling and degradation kinetics

AbstractFocus of the present studies was to synthesize a novel pH sensitive and thermoresponsive hydrogel which may show swelling behavior suitable for drug delivery at colon part of body. For this purpose, starch was copolymerized with methyl-3-aminocrotonate through free radical polymerization. The structural and thermal characterization of wheat starch/methyl-3-aminocrotonate hydrogel was carried out by XRD, FTIR and TGA. FTIR and XRD confirmed successful formation of the gel. Thermal data were further subjected to the isoconversional method for the determination of kinetic triplet (activation energy Ea, frequency factor A and g(α) function) to predict mechanism for thermal degradation of the synthesized gel. The first step showed a complex mechanism of thermal degradation, i.e., A2 followed by A3/2. Thermodynamic parameters ΔS* and ΔG* were also calculated. Moreover, swelling investigations unveiled these gels to be pH sensitive and thermoresponsive. The swelling percentage markedly increased with increasing pH and temperature. Kinetic order of swelling, diffusion mechanism and network parameters (i.e., molecular weight between cross-links and volume faction of polymers) of the synthesized hydrogel was also determined.

Fabrication of novel acrylic-based hdrogel for controlled release of organic and inorganic fertilizers

The preparation of various samples of ebonite vulcanizates and their physico-mechanical properties have been investigated using standard methods. This work explores the production of ebonite dust, production of ebonite vulcanizates and investigation of the characterization of the ebonite. Five different ebonite materials-labeled A, B, C, D, and E with sulphur content in parts per hundred grams of rubber (Phr) of 32, 34, 36, 38 and 40 respectively were produced. The physico-mechanical properties carried out were tensile strength, hardness and abrasion resistance. The tensile strength (MPa) for sample A, B, C, D and E were 5.6, 3.5, 4.7, 1.7 and 2.0 respectively while the abrasion (%mass loss) were 8.49, 4.24, 2.59, 1.08 and 1.05 respectively and the hardness (IRHD) being 63, 64, 65, 70 and 82.The results show that the preparation of ebonite from natural rubber as a base polymer is feasible considering the results of characterization obtained.T caffeic cid-derived polyether, namely poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl) ethylene] or poly[3-(3,4-dihydroxyphenyl) glyceric acid] (PDPGA) was isolated and identified in the water-soluble, high-molecular weight fractions obtained from extracts of different species of Boraginaceae family. According to data of 13C, 1H NMR, APT, 2D 1H/13C HSQC, 1D NOE and 2D DOSY experiments the polyoxyethylene chain is the backbone of the polymer molecule. 3,4-Dihydroxyphenyl and carboxyl groups are regular substituents at two carbon atoms in the chain. The repeating unit of this regular polymer is 3-(3, 4-dihydroxyphenyl) glyceric acid residue. Most of the carboxylic groups of PDPGA from Anchusa italica and Symphytum grandiflorum unlike the polymer of S. asperum, S. caucasicum and S. officinale are methylated. The 2D DOSY experiment gave the similar diffusion coefficient for the methylated and non-methylated signals of PDPGA. Both sets of signals fell in the same horizontal. This would imply a similar molecular weight for methylated and non-methylated polymers.Then basic monomeric moiety of this polymer, 3-(3, 4-dihydroxyphenyl) glyceric acid (DPGA) was synthesized via Sharpless asymmetric dihydroxylation of trans-caffeic acid derivatives using an osmium catalyst. Besides, it is well known that epoxides are valuable synthons in organic synthesis and have been introduced into pharmaceutical applications. Subsequently, the building block for the production of derivatives of PDPGA, methyl 3-(3,4-dimethoxyphenyl)glycidate was synthesized based on the Darzen reaction or by oxidation of trans-caffeic acid with oxone in order to produce in future derivatives of synthetic analogue of natural polymer through ring-opening polymerization of 2,3-disubstituted oxirane. PDPGA is endowed with intriguing pharmacological properties as anti-complementary, antioxidant, anti-inflammatory, burn and wound healing and anticancer properties. S. caucasicum PDPGA and DPGA exerted anti-cancer efficacy in vitro and in vivo. However, our results showed that anticancer efficacy of PDPGA is more effective compared to its synthetic monomer. Overall, this study identifies S. caucasicum PDPGA as a potent agent against PCA without any toxicity, and supports its clinical application.

Defluoridation of aqueous solutions by nanocomposite of MgAl2O4 and MA-VA-AA polymer: kinetics and mechanism

AbstractA nanocomposite of co-precipitatively synthesized MgAl2O4 and methyl acrylate-vinyl acetate-acrylic acid polymer was prepared through radical polymerization mechanism. The synthesized material was characterized by XRD, TGA, DSC, and SEM. XRD analysis of magnesium aluminate confirms the single spinel phase with average crystallite size of 33 nm. Adsorption of fluoride on the nanocomposite was studied at 308 K. The adsorption data were fitted to Freundlich, Langmuir, and Flory–Huggins models. Better correlation and comparable values of theoretical and experimental adsorption capacities (qe) indicated that the adsorption process followed pseudo-second-order kinetics. Mechanism of the adsorption process was investigated by applying Bingham’s and intraparticle diffusion models. Deviation from linearity of Bingham’s plot and significant value of intercept obtained from intraparticle diffusion model showed that both the film diffusion and pore diffusion processes may be the rate-controlling steps. Moreov...

Development of new multifunctional terpolymer sorbent for proteomics applications

Determination of the availability of phases for specific separations is an important task achieved by a separation chemist. This becomes vital when the complex samples like biofluids are dealt with in proteome science. The work presented here involves the synthesis and application of terpolymeric sorbent with different functionalizations adopted for the selective enrichment of biomolecules of interest from biological fluids. Synthesis of terpolymer was carried out by the radical polymerization of monomers: methyl acrylate, acrylic acid and vinyl acetate with diethylene glycol dimethacrylate as cross-linking agent, benzoyl peroxide as initiator and chloroform as a porogenic solvent. Characterization was done through Fourier transform infrared spectroscopy, scanning electron microscopy and nitrogen adsorption porosimetry. The polymer was further modified to immobilized metal ion affinity chromatographic material, with immobilized Fe(3+)/La(3+) ions that allowed phosphopeptide enrichment from tryptic digests of standard proteins as well as milk, egg yolk and human serum. Sensitivity of enrichment down to 50 fmol was achieved in the presence of complex protein background as bovine serum albumin. Hydrophobicity was introduced through octadecyl amine, which provides comparable results to ZipTip C18/C4 for desalting of complex mixtures of all caseins. Analysis of the enriched content was performed by Matrix Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS).