Anomalous Diffusion Mechanism Research Articles

PH-responsive hybrid magnetic polyelectrolyte complex based on alginate/BSA as efficient nanocarrier for curcumin encapsulation and delivery

Curcumin-loaded hybrid magnetic nanoparticles (HMNPs) were formulated using a simple and green method. At first, surface of Fe3O4 nanoparticles was modified using alginate (ALG), and magnetic ALG/Fe3O4 nanoparticles with a size of 33 nm and a zeta potential of -25 mv were prepared. Then, a complex including bovine serum albumin (BSA) and poly((3-acrylamidopropyl)trimethylammonium chloride) (p(APTMACl)) was prepared and optimized. The behavior of the BSA/p(APTMACl) complex was evaluated as a function of pH and protein/polymer ratio by UV–Vis spectroscopy, zeta potential, and DLS analysis. Finally, the hybrid complex of BSA/p(APTMACl)@ALG/Fe3O4 were prepared using mixing of the BSA/p(APTMACl) and ALG/Fe3O4 systems with opposite charges via electrostatic interactions. The prepared BSA/p(APTMACl) @ALG/Fe3O4 complex was named hybrid magnetic nanoparticles (HMNPs) and characterized by UV–Vis spectroscopy, SEM, FT-IR, TGA, XRD, VSM, and AFM. Three samples including pure Fe3O4, ALG/Fe3O4, and the final HMNPs exhibited no cytotoxic effect on MCF-7 breast cancer cell using the MTT assay. MTT assay to test the antitumor activity of bare and encapsulated-curcumin against MCF-7 cells showed BSA/p(APTMACl)@ALG/Fe3O4 nanoparticles are able to stabilize the curcumin anti-cancer drug and also enhancing the antitumor activity of the encapsulated curcumin. After loading of curcumin with a high efficiency of 95%. The accumulative release profiles of curcumin were investigated at 37 °C in phosphate buffered saline (PBS, pH 3 and 7.4). The release of curcumin-loaded HMNPs followed the Korsmeyer-Peppas equation and anomalous (non-fickian) diffusion mechanism at pHs 3 and 7.4.

Sustained release of ketorolac tromethamine from poloxamer 407/cellulose nanofibrils graft nanocollagen based ophthalmic formulations

There has been extensive utilization of poloxamer 407 (PM) for the delivery of various ophthalmic drugs aimed at efficient ophthalmic drug delivery approach for longer precorneal residence time along with acceptable bioavailability of drugs. We have studied the effect of nanocellulose grafted collagen (CGC) on the performance of in situ gels based on PM for the controlled in vitro release of Ketorolac Tromethamine (KT). CGC has shown great influence evident by the reduction in PM critical gelation concentration, increased gel strength, and prolonged the release of loaded drugs compared with the virgin PM gel. The engineered nanocomposite formulations established an anomalous diffusion mechanism along with a Fickian diffusion controlled drug release for 1.5 & 1.75 w/v% CGC reinforced PM. Hence, the synthesized in situ nanocomposites are potential candidates for ophthalmic drug delivery system.

Non-classical interstitial sites and anomalous diffusion mechanisms in hcp-titanium

It is well known that Fe, Co and Ni are characterised by abnormally fast diffusivity in the hcp phase of Ti (α-Ti). Their diffusivity values are 105 times higher than self-diffusion data, which is atypical for vacancy-mediated diffusion yet too slow for interstitial diffusion. Also, addition of Fe, Co and Ni appears to accelerate the solvent diffusivity, with dramatic ramifications on a number of diffusion-controlled mechanisms. The fast diffusivity of these elements in α-Ti seems to be the result of their ability to dissolve both interstitially and substitutionally. In fact, while the majority of Fe, Co and Ni atoms sit substitutionally within the hcp lattice, a small concentration of these solute atoms can move very fast through interstitial sites, determining the high diffusion coefficient values. In this work, a combination of density functional theory and Kinetic Monte Carlo simulations is used to investigate possible migration processes for both solute and solvent atoms and their effect on the macroscopic diffusivity. We find that traditional classical interstitial sites are unsuitable for these solute atoms, and that alternative interstitial sites are instead preferred. Calculations confirm that the fast diffusivity of these solute atoms is a result of their ability to diffuse both interstitially and by vacancy-mediated mechanisms, yielding excellent agreement with experimental values. It is possible for these solute atoms to swap position with solvent atoms without the presence of vacancies, leading to an accelerated solvent diffusion in the presence of relatively dilute levels of these solute elements.

Development of Alginate- Neusilin US2 (Magnesium alumino-metasilicate) micro-composite hydrogel beads for oral sustained release of cilnidipine: a statistical optimization

ABSTRACTIn presented work Alginate-Neusilin US2 micro-composite beads (MCBs) were formulated and optimized for oral delivery of cilnidipine (CIL). Optimized formulation of CIL loaded MCB (BA-O) exhibits particle size (1.55 ± 0.05mm), entrapment efficiency (82.35 ± 1.5%), and drug release after 12h (69.27 ± 2.2%). In vitro drug release indicates sustained drug release behavior following anomalous diffusion mechanism. The desirability function helps in formulating a new formulation with desired values of response. Furthermore, multiple linear regression analysis (MLRA) helps to predict influence of independent variables on dependent variables. The optimized MCB can be sorted as novel approach for sustaining CIL release profile to get maximum health benefits.

FORMULATION, DEVELOPMENT AND IN VITRO EVALUATION OF TRAMADOL EXTENDED RELEASE TABLETS

Objective: The objective of the present study was to develop “once daily” extended release tablets of tramadol (100 mg) by wet granulation using hydrophilic polymer like hydroxy propyl methyl cellulose K100M,K15M and polyethylene oxide (PEO).
 Methods: The tramadol matrix tablets were prepared by using different polymers like hydroxy propyl methyl cellulose (HPMC K15M and K100M), polyethylene oxide (PEO) as the nontoxic and easily available suitable matrix system. The extended release tablets of tramadol (400 mg) were prepared wet granulation technique. Different pre compression and post compression were performed. In vitro dissolution tests were performed and percentage drug release was calculated. The fourier-transform infrared spectroscopy (FTIR) studies conducted on pure drug tramadol and the optimize formulation (T6). Different release models like zero order, first order, higuchi and Korsemeyer-Peppas were applied to in vitro drug release data in order to evaluate the drug release mechanisms and kinetics.
 Results: Pre compression and post compression parameters satisfied with pharmacopeia specifications. The In vitro release studies were performed using USP type II apparatus showed that optimized formulation T6 consisting of polyethylene oxide (PEO) with 25 mg of the polymer was found to extended release of tramadol over a period of 24h. The optimized formulation T6 followed the zero order kinetics as correlation coefficient (r2) values are higher than that of first-order release kinetics. In order to understand the complex mechanism of drug release from the optimized formulation T6 matrix system, the in vitro release rate were fitted to Korsemeyer-Peppas model and the release exponent value (n) obtained was 0.82105 exhibited anomalous (non fickian) diffusion mechanism.
 Conclusion: The present study shows that polyethylene oxide was found to play a great role in controlling release of tramadol from the matrix system. Accordingly it can be concluded that the formulation is robust in the performance is less likely to be affected by the various factors studied.

Pectin-chitosan conjugated nanoliposome as a promising delivery system for neohesperidin: Characterization, release behavior, cellular uptake, and antioxidant property

Neohesperidin (NH) is a flavanone glycoside compound possessing diverse biological activities. However, NH is unstable in physiological condition and poorly soluble in water, and thereby it may show limited bioavailability. The aim of the present study was to facilitate the controlled delivery of NH in simulated gastrointestinal (GI) tract with enhanced cellular uptake using biopolymer conjugation onto nanoliposome (NL). The carrier systems were characterized by dynamic light scattering, HPLC analysis, and Fourier transform infrared spectroscopy. The biological activity was analyzed by in vitro antioxidant activity, rhodamine (Rh123)-assisted cellular uptake, and acrylamide (AA)-induced ROS model on Caco-2 cells. The results confirmed the size of nanocarriers fall in the range of 87–225 nm, well-encapsulation of NH, and conjugation of chitosan (CH) and pectin (P). In vitro digestion study revealed that P and CH-conjugated-nanoliposomes (P-CH-NL) significantly controlled the NH release following by anomalous diffusion mechanism, and preserved around 72–78% of NH in GI condition. The ABTS antioxidant activity, DPPH free radical scavenging capacity, and ferric reducing activity indicated that conjugated-nanoliposomes can preserve greater antioxidant activity after GI digestion. In vitro cellular uptake study showed enhanced Rh123 uptake by carrier systems, particularly P-CH-NL exhibited the highest uptake of around 141% followed by CH-NL (129%) and NL (100%). Cytotoxicity results also exposed that conjugated-nanoliposomes can significantly protect the human Caco-2 cells from AA-induced ROS generation. Conclusively, this work provides a promising approach for the controlled delivery of lipophilic natural products with enhanced cellular uptake at colonic epithelial cells and greater biological activity.

Hollow mesoporous hydroxyapatite nanostructures; smart nanocarriers with high drug loading and controlled releasing features

We report the development of effective drug loaded nanocarriers to combat multidrug resistant infection especially in case of osteomyelitis. The hollow mesoporous hydroxyapatite nanoparticles (hmHANPs) and solid/non-hollow hydroxyapatite nanoparticles (sHANPs) were synthesized by core–shell and co-precipitation techniques respectively. High encapsulation of the drug (ciprofloxacin) was observed in hmHANPs as compared to sHANPs, which may be due to the hollow porous structure of hmHANPs. These nanoparticles were characterized by scanning electron microscope (FESEM), N2 adsorption/desorption, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Thermogravimetric analysis (TGA). Approximately 80% of the encapsulated drug was released at pH 4.5 within 5 days in case of hmHANPs while at pH 7.4, a sustained drug release profile was obtained and only 48.73% of the drug was released after 9 days. The results of kinetic drug release revealed that drug loaded hmHANPs showed fickian diffusion and anomalous drug diffusion mechanism at pH 4.5 and 7.4 respectively. Owing to their porous structure and high drug loading capacity, hmHANPs showed enhanced antibacterial activity against Staphylococcus aureus and Escherichia coli (drug resistant strains of osteomyelitis) in comparison to that with sHANPs. In addition, hmHANPs showed a pH sensitive drug release profile, high surface area (105.33 m2/g) with increased pore volume (0.533 cm3/g) and superior antimicrobial activity against osteomyelitis as compared to sHANPs.

Effect of pH and temperature on the release kinetics of urea from wheat-gluten membranes obtained by electrospinning

Optimal usage of urea-based fertilizers can increase their use efficiency and reduce pollution. A new alternative for prolonged-release (PR) urea based on wheat-gluten (WG) membranes obtained by electrospinning was studied. The effect of pH and temperature on the release rate of urea and its transport mechanisms were evaluated. At pH 4, 7, and 10, the equilibration times obtained were 1, 3, and 5 h, respectively. Additionally, at a higher temperature, a larger amount of urea was released into the medium. The Ritger–Peppas model suggests that with pH 4 and pH 10, at 25 °C, there is an anomalous diffusion mechanism. On the other hand, the remainder of the release conditions tested showed a release mechanism of urea by simple diffusion. According to the results, a potential application of these wheat-gluten membranes on the release system of urea for soils with pH 7 and soil temperatures between 25 and 40 °C is proposed.

Fabrication of core–shell PLGA/PLA–pNIPAM nanocomposites for improved entrapment and release kinetics of antihypertensive drugs

Polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) are two commonly applied biodegradable polymers for the preparation of nanocomposites used in drug-delivery systems. However, these polymers lack desirable attributes such as resistance to aggregation during long-term storage due to lyophilisation. To improve their efficacy, in this work, PLA and PLGA were encapsulated within a shell of poly(N-isopropylacrylamide) (pNIPAM) using a single emulsion technique followed by an aqueous free radical precipitation polymerisation process, yielding core–shell PLA/PLGA–pNIPAM nanocomposites. The nanocomposites were characterised using zeta potential, dynamic light scattering, and transmission electron microscopy analyses and were further applied as a delivery system for ramipril, an antihypertensive drug. The drug-loaded PLGA–pNIPAM core–shell nanoparticles exhibited a higher drug content (91%) and entrapment efficiency (78%) than their PLA counterparts. An in vitro release study of the formulations at pH 7.3 in phosphate-buffered saline indicated that PLGA was more efficient than PLA with a sustained release of 86% of ramipril from the polymer matrix within 24h. Furthermore, to determine the release kinetics, the data were fitted to Korsmeyer–Peppas and Higuchi models; the release of ramipril from the polymer matrix followed zero-order rate kinetics and an anomalous (non-Fickian) diffusion mechanism.

Characterization of Microcapsule Containing Walnut (Juglans regia L.) Green Husk Extract as Preventive Antioxidant and Antimicrobial Agent.

Background:Walnut green husk (WGH) extract has been known as potential preventive and therapeutic antioxidants and antimicrobials due to its high polyphenol content. In this study, preparation of spray dried WGH extract-loaded microcapsules by maltodextrin and its blending with two other natural biodegradable polymers, pectin, or alginate were investigated.Methods:In this study, encapsulation efficiency (EE), total phenol content (Folin–Ciocalteu reagent method), antioxidant (DPPH scavenging assay) and antimicrobial activities (agar well diffusion method) structural (SEM and FTIR studies), and release properties of WGH extract-loaded microcapsules were investigated.Results:High retention of phenolic content in microcapsules indicated the successful encapsulation of WGH extract. Addition of biopolymers to maltodextrin matrix has a positive effect on EE and other properties of microcapsules. The microcapsules prepared with mixture of maltodextrin and pectin had higher EE (79.35 ± 0.87%) and total phenolic (TP) content (56.83 ± 1.04 mg gallic acid equivalents [GAE]/100 g) in comparison to maltodextrin and alginate mixture (EE: 75.21 ± 0.24%, TP content: 54.33 ± 1.53 mg GAE/100 g) and maltodextrin only matrix (EE: 72.50 ± 1.00%, TP content: 50.67 ± 1.35 mg GAE/100 g). Extract-loaded microcapsules also showed nearly spherical structure, good antioxidant (with the percentage DPPH inhibition ranged from 75.17 ± 1.42% to 80.87 ± 2.29%), and antimicrobial properties (with mean inhibition diameter zone ranged from 7.76 ± 0.86 mm to 11.53 ± 0.45 mm). Fourier transform infrared analyses suggested the presence of extract on microcapsules. The in vitro extract release from microcapsules followed an anomalous non-Fickian diffusion mechanism with almost complete release.Conclusions:WGH extract microcapsules can be used as novel and economic bioactive phytochemical and therapeutic agents to prevent oxidation and microbial activity.

In situ gel of Nifedipine: an approach for extended release with Zero order kinetics

Nifedipine was formulated as in situ gel forming tablet using natural and synthetic polymers in combination. The tablets were prepared with various drug polymer ratios of HPMC, Xanthum gum and Guar gum by direct compression method. The polymers has the potential in retarding drug release to its gelling nature and ability of entrapping the drug within the gel .The swelling property of these polymers helps to improve the dissolution rate of drug. The tablets were evaluated to thickness, weight variation,drug content, hardness, friability, in vitro swelling and in vitro release studies. Hardness of the tablets were ranged from 4.3 to 6.0 kg/cm2. All the formulations showed compliance with Pharmacopoeal standards. FT-IR study did not showed any possible interaction between Nifedipine and excepients. The percentage of release were from 38.12 to 76.95%. The dissolution studies indicated that formulation F4 was most successful of the study and it exhibited anomalous(non-fickian)diffusion mechanism Such a drug delivery system may provide a viable alternative for effective management of hypertension and other related disorders. With respect to the application in controlled release systems, the overall delivery rate from a polymeric specimen is expected to be a function of swelling and disintegration characteristics of a specimen, and therefore, the weight uptake can be considered a measure of the release only in the case of polymers with low water solubility and increased stability to hydrolysis.

Preparation of a pH sensitive hydrogel based on dextran and polyhydrazide for release of 5-flurouracil, an anticancer drug

A new hydrogel network was designed to study its capability in hydrophilic drug delivery. Two sets of chemically cross-linked hydrogels were prepared under mild conditions with different cross-linking densities. The precursors obtained by modification of a natural polymer and a synthetic polymer. Oxidation of dextran, natural polymer, produced dextran aldehyde (DA) with reactive aldehyde functionalities and aminolysis of polysuccinimide (PSI) resulted in polyhydrazide (PHZ) formation with reactive hydrazide groups. These two polymers reacted via Schiff-base reaction to form hydrozone linkages as cross-linking sites. The resultant gels showed no toxicity towards L929 mouse fibroblast cells. These biocompatible hydrogels were used for encapsulation and release of 5-flurouracil (5-FLU), a hydrophilic anticancer drug. 5-FLU was released in almost two days from high cross-linked matrix through an anomalous diffusion mechanism. Swelling, degradation and mechanical properties of these networks were studied, and it was observed that the cross-linking density can change the characteristics of the gel. Hydrogel with higher cross-linking density showed longer degradation and lower swelling index and stiffer network compared to the system with lower cross-linking density. The degradation and release behaviour of the gels were sensitive to the pH of medium suggesting faster hydrolysis of hydrozone bonds in lower pH environment.

Curing of polyfurfuryl alcohol resin catalyzed by a homologous series of dicarboxylic acid catalysts. II. Swelling behavior and thermal properties

ABSTRACTPolyfurfuryl alcohol (PFA), as a bio‐based resin made from lignocellulosic materials, was crosslinked using a homologous series of dicarboxylic acid catalysts consisting of oxalic, succinic, and adipic acids, which are different in their dissociation constants. Swelling behavior, thermal stability, and non‐oxidative char residue of the resulting networks were characterized as a function of the acids strength and their concentration. Swelling of the networks were investigated at room temperature in eight solvents differing in molecular size and solubility parameter. Using acetonitrile as a solvent, the swelling mechanism was explored by applying kinetic models to the swelling data. Dynamic swelling studies during 16–30 days supported non‐Fickian and anomalous diffusion mechanism in highly crosslinked samples supporting PFA chain rigidity and high crosslinking density of the networks. Polymer–solvent interaction parameter, molecular weight between crosslinks and crosslinking densities were also determined. According to the results, the extent of PFA crosslinking and non‐Fickian behavior of the swelling solvent diffusion through the networks are strongly dependent on the concentration and dissociation characteristics of the catalysts used. Thermal stability studies showed no significant differences between the compositions, up to 900 °C. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45770.

Anomalous diffusion and stress relaxation in surfactant micelles.

We investigate the mechanisms of anomalous diffusion in cationic surfactant micelles using molecular dynamics simulations in the presence of explicit salt and solvent-mediated interactions. Simulations show that when the counterion density increases, saddle-shaped branched interfaces manifest. In experiments, branched structures exhibit lower viscosity as compared to linear and wormlike micelles. This has long been attributed to stress relaxation arising from the sliding motion of branches along the main chain. Our simulations reveal a mechanism of branch motion resulting from an enhanced counterion condensation at the branched interfaces and provide quantitative evidence of stress relaxation facilitated by branched sliding. Furthermore, depending on the surfactant and salt concentrations, which in turn determine the microstructure, we observe normal, subdiffusive, and superdiffusive motions of surfactants. Specifically, superdiffusive behavior is associated with branch sliding, breakage and recombination of micelle fragments, as well as constraint release in entangled systems.

FLOATING-BIOADHESIVE MATRIX TABLETS OF HYDRALAZINE HCL MADE OF CASHEW GUM AND HPMC K4M

Objective: The objective of this paper was to prepare and evaluate floating-bioadhesive cashew gum-hydroxypropyl methylcellulose (HPMC K4M) matrix tablets for the gastro-retentive release of hydralazine HCl.Methods: The cashew gum-HPMC K4M matrix tablets of hydralazine HCl were prepared by direct compression method with the incorporation of sodium bicarbonate and citric acid as effervescent agents. Drug contents, weight variations, hardness, friability, in vitro swelling, in vitro floatation, ex vivo mucoadhesion and in vitro drug release of these matrix tablets were evaluated.Results: Drug contents, weight variations, hardness and friability of these matrix tablets were within the compendia limits. These tablets were floated well in vitro over 12 h in simulated gastric fluid (SGF, pH 1.2) with minimum lag time. The ex vivo adhesion of these matrix tablets with goat intestinal mucosa exhibited good bioadhesion in a wash off test. All these cashew gum-HPMC K4M floating-bioadhesive matrix tablets of hydralazine HCl showed in vitro sustained releases of hydralazine HCl over 12 h in SGF, pH 1.2. The in vitro hydralazine HCl followed Korsmeyer-Peppas kinetic model and anomalous (non-Fickian) diffusion mechanism. The drug-polymer compatibility analysis by FTIR spectroscopy indicated the absence of any drug-polymer interaction within this cashew gum-HPMC K4M floating-bioadhesive matrix tablets of hydralazine HCl.Conclusion: The results clearly indicate a promising potential of the use of cashew gum as matrix forming a material with HPMC K4M to prepare matrix tablets for gastro retentive delivery of hydralazine HCl through the combined approach of floatation and bioadhesion to reduce the dosing rate with better patient compliances.

Anomalous diffusion based on fractional calculus approach applied to drying analysis of apple slices: The effects of relative humidity and temperature

AbstractThe objective of this research was to evaluate the diffusion mechanism based on Fick's second law and anomalous diffusion modifying the drying operating conditions temperature (T) and relative humidity (RH) on apple slices (cv. Granny smith). Drying was performed at 30 °C, 40 °C, 50 °C and 30%, 50%, 70%RH based on a 32 experimental design. The drying curves were analyzed to determine the effective diffusion (Deff) using two methods: Fick's second law and anomalous diffusion model based on fractional calculus approach. Our results showed that the anomalous diffusion mechanism fit the experimental data better and revealed a super‐diffusive behavior (α > 1). Therefore, Deff values were estimated using the anomalous diffusion model with α = 1.735. With respect to the use of anomalous diffusion model solution based on fractional calculus at different operations conditions allow to get better fitting of drying data than second Fick's law model, even keeping the Arrhenius behavior of Deff with temperature.Practical applicationsDiffusion process is typically analyzed using models based on Fick's second law. However, several assumptions inherent in Fick's second law are not fulfilled in food materials (e.g., structural heterogeneity). In addition, Fick's second law does not consider structural variations during the drying process, and it is well known that fruits such as apples experience significant structural changes during drying. Fractional calculus is a tool for mathematically representing the anomalous diffusion of solutes whose movements can be faster or slower than postulated in Fick's second law due to food structure. In general, with second Fick's law model not good fitting to data are obtained, therefore the prediction capacity of the model is limited. Based on this, anomalous diffusion solution based on fractional calculus was applied. The results showed good fit the data to the model, and also by the time exponent (α) is possible to identify the kind of diffusion process.

Formulation and In vitro Evaluation of Floating Microspheres of Misoprostol

Misoprostol is a synthetic prostaglandin PGE1 analogue, which has proved to be an effective anti-secretory agent for oral use. The major indications of Misoprostol are in the prevention and treatment of NSAID-induced gastric and duodenal ulcers. Its half-life is 20-40 minutes. More than one third of patients with ulcers are resistant to H2 antagonists. So, these patients can be healed on Misoprostol. The objective of the present study was to formulate gastroretentive floating drug delivery system of an antiulcer drug Misoprostol. Floating microspheres of Misoprostol were prepared by an emulsification solvent evaporation technique using hydroxy propyl methyl-cellulose (HPMC K 100M) and ethyl cellulose. The percentage yield and drug entrapment efficiencies of these floating microspheres were within the range between: 70 ± 2.8 to 98 ± 2.9 % and 39.27 to 82.39 %, respectively. The determined mean particle size for all the microspheres were 250 ± 7.28 to 400 ± 2.32 µm. The flowability of these microspheres was found good. A high performance liquid chromatography (HPLC) method with ultra-violet (UV) detection was selected for the method of analysis. The drug release was found to delay for 12 hours with the increasing drug to polymer ratio. The drug release kinetics followed Korsemeyer-Peppas and Higuchi model with anomalous (non-Fickian) diffusion mechanism for the drug release. The FTIR and DSC studies showed that there was an absence of chemical interaction between the drug and the excipients. The in vitro drug release from Misoprostol floating microspheres showed the drug release was dependent on the drug to polymer ratio. The drug release was found delayed with the increasing drug to polymer ratio.

Transitions in asymmetric spike patterns with anomalous diffusion

Complex natural systems at times manifest transitions between disparate diffusive regimes. Efforts to devise measurement techniques capable of identifying the cross-over moments have recently borne fruit, however interpretation of findings remains contentious when the bigger picture is considered. This study uses a phenomenological reaction–diffusion model to obtain a sufficiently general, yet tractable description for the dynamics of a pattern qualitatively redolent of molecular clusters subject to transient anomalous diffusion mechanisms. The resulting system of equations is investigated for substantiation of the reasons difficulties are encountered when attempting to distinguish between various diffusive regimes in experimental settings: a non-monotonic dependence of the pattern’s evolution on parameters defining the diffusion mechanism is a common occurrence, as is a non-injective mapping between a given sequence of diffusion regimes and ensuing drift behaviour. Albeit formally the developed description is limited to piecewise constant anomaly functions, it is useful in computation of approximations to smooth realistic transitions.

Characterization of natural polymers from jackfruit pulp, calendula flowers and tara seeds as mucoadhesive and controlled release components in buccal tablets

Identification and physiochemical parameters such as solubility, loss on drying, viscosity, pH, swelling index, starch and gum constituents were determined in natural polymers and showed satisfactory results. Spectral studies established the compatibility of natural polymers. The drug release kinetics in preliminary trial batches showed that tablets containing natural mucilages and gum showed a prolonged drug release comparable to Carbopol 974P and Methocel K4M. Also, all tablets showed a satisfactory drug permeability flux. Acute toxicity studies confirmed the safety of natural polymers. Using response surface method supported by 23 factorial design, the optimized buccoadhesive tablets (C1) with drug release at 8h (R8h, %) of 53.48±0.048% showed controlled release over ≥8h and followed the Korsmeyer-Peppas model with anomalous (non-Fickian) diffusion mechanism. Mucoadhesive strength was found to be 42.71±0.49g. Comparative dissolution study between prepared and marketed formulation showed that there was no significant difference in drug release profile having similarity factor 82.97. In vivo study for optimized formulation of the buccoadhesive tablets showed the better absolute bioavailability (71.26%) against the oral solution (51.22%). Histological study confirmed non-irritant nature and stability study indicated stability of the formulation.

Design and development of Albizia stipulata gum based controlled-release matrix tablets in cancer therapeutics

The present study deals with the development of natural macromolecule gum Albizia stipulata (AS) based novel pharmaceutical excipient for the controlled-release of paracetamol (PC). Central composite design (CCD) two-factor, five-level was used for the optimization of independent variables AS gum and compression force (CF) based on desired response variable drug release (DR) of paracetamol matrix tablets (PCMT). The optimized PCMT was prepared by wet granulation method and screened for pre- and post- compression parameters, and were characterized. The optimized PCMT (F14) formulation showed favorable in vitro release of PC (65%) in 12h, and the release kinetics followed zero order anomalous diffusion mechanism. AS gum exerted significant (p<0.001) anticancer activity with 98.25% inhibition at 2000μg/mL (IC50=179.12μg/mL) against A549 cell line. PC and PCMT showed 78.56% inhibition (IC50 value=856.58μg/mL) and 93.68% inhibition (IC50 value=396.35μg/mL) respectively, symbolizing that the gum remarkably potentiated the anticancer effect of PC in formulation after 24h treatment by inducing apoptosis. This is the first report on A. stipulata gum as a promising biopolymer for drug delivery application in cancer therapeutics.