Bead Formulations Research Articles

Design of atrazine containing polysaccharide based slow release formulations to control environmental hazards

Atrazine is more reliable, flexible, effective and less expensive herbicide than any other available weed control approaches. However, easy leaching of atrazine is a matter of great environmental and health concern which limits its strong recommendation for practical applicability. Hence, controlled release formulations of atrazine, specially based on natural polysaccharide, are required for delivery and resolve the problems associated with conventional formulations. In the present work, slow release atrazine containing alginate-agar based bead formulations have been prepared and characterized by scanning electron micrography, Fourier transform infrared spectroscopy and swelling studies. The release of atrazine from the beads occurred through non-Fickian diffusion mechanism. The release of atrazine from the beads in the soil has been observed slower and lesser in soil as compared to the in vitro release. Besides providing the slow release of atrazine, these formulations after degradation may enhance the fertility of the soil.

Formulation and characterization of polysaccharide beads for controlled release of plant growth regulators

Owing to their chemical, physical, and functional characteristics, polysaccharides are considered to be the most versatile natural polymers. As a result, their properties have been exploited in various fields of research in the biomedical, pharmaceutical, cosmetic, food, and agricultural industries. A property of special interest is their ability to form systems or materials with unique physicochemical characteristics, such as hydrogels and micro- and nanoparticles for controlled release of active compounds. In the present study, polysaccharide beads formulated from alginate, cellulose powder, cellulose nanocrystals, starch, and xylan were reinforced with kaolin and surface-modified with polyethylenimine (PEI), a positively charged polyelectrolyte. Addition of kaolin improved the mechanical strength of the beads. Modification of the surface of the beads with PEI facilitated better control of the release rate of the plant growth regulator, phenylacetic acid (PAA). The physical properties of the beads were characterized by optical and scanning electron microscopy, and their mechanical strength was determined by an Instron 5565 Tensile Testing Machine. Cumulative release of PAA was measured by UV–Vis spectroscopy.

Formulation and stability evaluation of 3D alginate beads potentially useful for cumulus–oocyte complexes culture

Ovarian follicle encapsulation in synthetic or natural matrixes based on biopolymers is potentially a promising approach to in vitro maturation (IVM) process, since it maintains follicle 3D organisation by preventing its flattening and consequent disruption of gap junctions, preserving the functional relationship between oocyte and companion follicle cells. The aim of the work was to optimise physico-chemical parameters of alginate microcapsules for perspective IVM under 3D environments. On this purpose alginate and cross-linking agent concentrations were investigated. Alginate concentration between 0.75% and 0.125% w/w and Mg2+, Ba2+, Ca2+ at concentration between 100 and 20 mM were tested. Follicle encapsulation was obtained by on purpose modified diffusion setting gelation technique, and evaluated together with beads, chemical and mechanical stability in standard and stressing conditions. Beads permeability was tested towards albumin, fetuin, pyruvate, glucose, pullulan. Results demonstrated that 0.25% alginate cross-linked in 100 mM CaCl2 beads is suitable to follicle encapsulation.

Exploitation of novel gum Prunus cerasoides as mucoadhesive beads for a controlled-release drug delivery

The present study deals with the formulation of pH-sensitive mucoadhesive beads using natural gum isolated from Prunus cerasoides (PC) in combination with sodium alginate (SA) for the controlled release of diclofenac sodium (DS). PC and SA composite (PC–SA), DS loaded SA (DS-SA) and DS loaded PC–SA (DS–PC–SA) beads were prepared by ionotropic gelation method. The absence of interaction between DS and PC–SA was shown by FTIR, DSC and TGA analyses. The optimized DS–PC–SA formulation exhibited mucoadhesive property and the controlled release of DS was achieved 68% in 12h. The in vitro release kinetics follows zero order with anomalous diffusion mechanism. Therefore, the formulated mucoadhesive beads with the novel gum are preferable for the controlled release of DS by prolonging the residence time of the drug in the gastrointestinal tract, overcoming the problems associated with the immediate release dosage forms of DS.

Alginate beads as a carrier for omeprazole/SBA-15 inclusion compound: A step towards the development of personalized paediatric dosage forms

The treatment of gastro-esophageal reflux disease (GERD) shows several issues among paediatric patients. This work aims to the formulation of enteric alginate beads loaded with omeprazole (OME) allowing age- and weight-related personalized dosages in children. OME was entrapped in SBA-15 mesoporous compound, characterized and loaded into alginate beads by prilling at different OME and alginate concentrations. The beads resulted of homogeneous size, spherical morphology and very consistent in drug loading and distribution. Formulations demonstrated limited swelling and release (about 10%) in simulated gastric fluid (SGF) after 2h and a prolonged release in simulated intestinal fluid (SIF), till 6h, due to a mixed diffusion-case II transport mechanism. The beads were superior to the market product, which showed lower release in SGF but immediate dissolution in SIF. The high alginate beads uniformity and release properties make them a potential novel tool for a personalized treatment of GERD in children.

Pectin beads loaded with chitosan–iron microspheres for specific colonic adsorption of ciprofloxacin

Residual antibiotics reaching the colon can induce severe deleterious effects on the colonic microbiota including the induction of resistance to antibiotics. To avoid the selection of ciprofloxacin resistance, chitosan–iron microspheres were encapsulated into pectin beads with the aim to specifically adsorb residual colonic ciprofloxacin, reducing its time of contact with the endogenous bacteria. In our study, the formulation of beads, their stability as well as their capacity to specifically adsorb ciprofloxacin in simulated digestive media was carried out. Beads incubated in simulated gastric and intestinal media were stable for 1 and 5 h, respectively. When incubated in simulated colonic medium, beads were then degraded by pectinases present in the medium. Coating with Eudragit® RS was needed to prevent the early adsorption of the antibiotic in intestinal medium. Adsorption studies in simulated colonic medium show that the adsorption capacity of chitosan–iron is not modified after encapsulation within pectin beads making clinically feasible the sequestration of residual ciprofloxacin reaching the colon.

Formulation, physicochemical characterization and in-vivo evaluation of ion-sensitive metformin loaded-biopolymeric beads

The demand on the controlled release of short acting antidiabetic drug, metformin (MT), has been increased dramatically. Thus, boosting the development of new sustained release formulations with contents of multi-micro-scaled particles. This paved the way for the preparation of MT-loaded Gellan gum (GG) microbeads through inotropic gelation technique. The prepared beads were characterized for the following parameters; yield and loading efficiency particle size, particles morphology and topography, swelling behavior, and in-vitro release studies. In view of any possible interactions, differential scanning calorimetry and infrared spectroscopy were performed. As an ultimate evaluation, the relative bioavailability of the sustained release beads was studied in healthy volunteers after oral administration in a fasted state compared to commercially available immediate and extended release tablets using a new validated HPTLC method for MT assay in urine. Results obtained revealed that the formulated Gellan beads were spherical in shape with less smooth surface in the micron range with high yield and entrapment efficiency. In-vitro release studies of the prepared beads were achieved up to 8 h. The prolonged release of MT can be explained through various factors among them; the swelling of the biopolymer and the ionic interaction between the drug and the GG. After oral administration, the AUC0−24, t1/2 and tmax of the prepared beads were of 246.74 ± 26.81 mg, 11.84 ± 2.79 and 7.17 ± 1.75 h, respectively, demonstrating its bioequivalence to the marketed products. In conclusion, the formulated GG microbeads exhibit potentials as an oral sustained release MT system.

Factorial design, preparation and characterization of new beads formed from alginate, polyphosphate and glycerol gelling solution for microorganism microencapsulation

The growing environmental concern in all segments of society has aroused the interest of the scientific community in the search for alternatives to reduce the use of pesticides, getting highlighted the use of antagonists microorganisms, as species of Trichoderma. Despite many years of research, several challenges such as lack of formulations, storage and transport conditions, which reduce the viability of microorganisms, hamper the application of this technology in large scales. A polymeric formulation that retains the characteristics and properties of the antagonist is of fundamental importance for an efficient and effective control of the disease to be fought. Encapsulation into beads may be an alternative to provide protection and maintain the properties of these microorganisms. In this paper, applying the factorial design tool, was studied a formulation having as independent variables the proportion of sodium alginate, sodium polyphosphate and glycerol aiming to increase the water activity (aW) of the beads. The beads were prepared using the technique of drip by simple ionic gelation of biopolymers in solutions of CaCl2 (2M). Characterization of beads was held by FTIR spectrophotometer and thermogravimetric analysis. Results indicate that the greater proportion of polyphosphate formulation was more significant for a larger aW into the beads. Preliminary results show that beads formulation with alginate, polyphosphate and glycerol was able to maintain the viability of spores of Trichoderma sp. for 120 days when stored at room temperature. The water activity (aW) of the samples was evaluated and had different responses that depended on the composition of granules. The surface chart represents the responses of aW for Ca-AGP beads. Figure shows the Pareto diagram, where it can be seen that only the concentration of polyphosphate was significantly variable in aW response. The distribution of the residuals (values predicted by the model vs. observed values) showed that the deviations were normally distributed and that there was a satisfactory correlation between the theoretical and experimental values.

Alginate beads of Captopril using galactomannan containing Senna tora gum, guar gum and locust bean gum

Gastro-retentive Captopril loaded alginate beads were prepared by an ionotropic gelation method using sodium alginate in combination with natural gums containing galactomannans (Senna tora seed gum, guar gum and locust bean gum) in the presence of calcium chloride. The process variables such as concentration of sodium alginate/natural polymer, concentration of calcium chloride, curing time, stirring speed and drying condition were optimized. Prepared beads were evaluated for various parameters such as flow property, drug content and entrapment efficiency, size and shape, and swelling index. Surface morphology of the beads was studied using scanning electron microscopy. In vitro mucoadhesion and in vitro drug release studies were carried out on the prepared beads. From the entrapment efficiency and dissolution study, it was concluded that galactomannans in combination with sodium alginate show sustained release property. The bead formulation F4 prepared using combination of sodium alginate and guar gums in the ratio 2:1 showed satisfactory sustained release for 12h. The release of Captopril from the prepared beads was found to be controlled by the swelling of the polymer followed by drug diffusion through the swelled polymer and slow erosion of the beads.

Influence of compression speed and deformation percentage on mechanical properties of calcium alginate particles

Hydrogel particles are often used as a carrier for immobilization of enzymes, polyphenolic antioxidants, whole microbial, plant or mammalian cells. In many processes, mechanical properties of alginate particles are essential due to their exposure to mechanical forces in production process. Determination and improvement of hydrogels mechanical properties is very important in prevention of the undesirable side effects during the manufacturing process and product application. The aim of this study was to define the mechanical properties of single particles submerged in water and in dry conditions using the compression method between two flat surfaces. The results indicated that the formulation of alginate beads and water loss during compression have significant influence on their mechanical behavior and stiffness. Calcium-alginate particles were produced using an electrostatic droplet extrusion technique, with an initial sodium alginate concentration of 1.5%w/v and calcium chloride (2.0% w/v) as gelling solution. The research findings were used to determine the influence of working conditions, sample deformation (10-50%) and different compression speeds (1-50mm/min) on mechanical strength of alginate beads. The Young?s modules and maximal forces for investigated deformation percentage of the alginate particles were determined from generated force-displacement and stress-strain curves during compression.

Aluminum Alginate–Montmorillonite Composite Beads for Defluoridation of Water

A novel alginate–montmorillonite biopolymer-clay composite bead formulation for water defluoridation was developed in this study. Montmorillonite was dispersed alginate solution, and the mixture was cross-linked in an aqueous solution of aluminum(III). The resulting cross-linked beads were characterized using FTIR, SEM, and mechanical measurements. In order to reveal the defluoridation capacity of the beads, batch adsorption experiments were carried out. Optimum conditions and effect of competing ions were investigated. Experimental data were modeled using several isothermal, kinetic, and thermodynamic models. Maximum Langmuir adsorption capacity was reached as 31.0 mg g−1 at 25 °C. It is also found that the adsorption is physical in nature and follows the Elovich kinetic model, and the fluoride removal efficiency is not affected by the presence of most competing anions. The results show that aluminum alginate–montmorillonite composite beads can be used as effective and natural sorbents for fluoride removal from water.

A randomized placebo-controlled double-blind study evaluating the time course of response to methylphenidate hydrochloride extended-release capsules in children with attention-deficit/hyperactivity disorder.

The purpose of this study was to assess the time of onset and time course of efficacy over 12.0 hours of extended-release multilayer bead formulation of methylphenidate (MPH-MLR) compared with placebo in children 6-12 years of age with attention-deficit/hyperactivity disorder (ADHD) in a laboratory school setting. This randomized double-blind placebo-controlled study included children 6-12 years of age with ADHD. Enrolled children went through four study phases: 1) Screening period (≤4 weeks) and a 2 day medication washout period; 2) open-label period with dose initiation of MPH-MLR 15 mg daily and individual dose optimization treatment period (2-4 weeks); 3) double-blind crossover period in which participants were randomized to sequences (1 week each) of placebo and the optimized MPH-MLR dose given daily; and 4) follow-up safety call. Analog classroom time course evaluations were performed at the end of each double-blind week. The primary efficacy end-point was the mean of the on-treatment/postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP)-Total scores over time points collected 1.0-12.0 hours after dosing. End-points were evaluated using a mixed-effects analysis of covariance. The evaluable population included 20 participants. The least-squares mean postdose SKAMP-Total score was higher for placebo than for MPH-MLR (2.18 vs. 1.32, respectively; p=0.0001), indicating fewer symptoms with MPH-MLR therapy than with placebo. No difference in SKAMP-Total score between participants who received sequence 1 or sequence 2 was noted. From each of hours 1.0-12.0, least-squares mean SKAMP-Total score was significantly lower for those receiving MPH-MLR than for those receiving placebo (p≤0.0261). Neither serious adverse events nor new or unexpected safety findings were noted during the study. MPH-MLR showed a significant decrease in SKAMP scores compared with placebo in children with ADHD 6-12 years of age, indicating a decrease in ADHD symptoms. The estimated onset was observed within 1.0 hour, and duration was measured to 12.0 hours postdose. ClinicalTrials.gov Identifier: NCT01269463.

Formulation and evaluation of Etodolac alginate beads prepared by ionotropic gelation for sustained release

Oral sustained release drug delivery system is getting greater attention due to its therapeutic advantages. Etodolac is a non-steroidal anti-inflammatory drug with potent analgesic and anti-arthritic properties. It has a short biological half life of 6.4 hours and is administered in a dose of 200-400 mg every 6-8 hours. In the present study, a suitable particulate system of Etodolac has been developed, by ionotropic gelation method for sustained release that would result in prolonged clinical efficacy, reduced frequency of administration and lesser side effects. Microbeads were prepared with and without using maize starch as polymer and were evaluated for particle size and size distribution analysis, flow properties, loose surface crystal study, entrapment efficiency, swelling ratio, percentage yield and drug content uniformity and invitro drug release. It was found that the particle size distribution of both formulations was varied within a narrow size range. Drug leaching (15.46 % ± 0.118) was more with presence of maize starch. Entrapment efficiency was retarded with the presence of maize starch. Swelling ratio (54.29 ± 0.151) suggested that maize starch incorporated microbeads swelled more to behave as a matrix for controlled drug delivery. Formation of highly viscous dispersion with the incorporation of polymer led to high percentage yield (51.48% ± 0.180). Drug release data was fitted into various kinetic models and indicated that the mechanism was according to Peppas model. The study revealed that the microbeads of Etodolac could be successfully prepared by ionotropic gelation technique with sustained release characteristics.

Steady-state bioavailability of extended-release methylphenidate (MPH-MLR) capsule vs. immediate-release methylphenidate tablets in healthy adult volunteers.

The objective of the study was to determine the relative bioavailability of an extended-release multilayer bead formulation of methylphenidate hydrochloride (MPH-MLR) 80mg vs. methylphenidate immediate-release (IR; Ritalin(®)) tablets as single and multiple doses in the fed state. A single-center, multiple-dose, randomized, open-label, two-period crossover study conducted in 26 healthy adults assigned to 4days of once-daily MPH-MLR 80mg or IR methylphenidate 25mg three times daily. MPH-MLR 80mg produced reproducible biphasic profiles of plasma methylphenidate concentrations characterized by a rapid initial peak, followed by a moderate decline reaching a plateau ~5 h post dose, then a gradual increase culminating in an attenuated second peak ~7h post dose. Maximum concentration was lower for MPH-MLR 80mg than IR methylphenidate 25mg three times daily on day 1 (23.70 vs. 31.47ng/mL); exposure was similar. The geometric mean ratios (MPH-MLR/IR methylphenidate [90% CI]) of log-transformed area under the plasma drug concentration-time curve to the last measurable observation (day 1: 0.88 [84.75-91.80]; day 4: 0.84 [81.16-86.94]), and area under the plasma drug concentration extrapolated to infinity (day 1: 0.93 [88.57-97.28]; day 4: 0.88 [84.48-91.17]) were within the 80-125% bioequivalence range. The mean±SD MPH-MLR 80-mg capsule day 4 area under the plasma drug concentration vs. time curve from 0 to 4h (74.5±15.2ng·h/mL) was greater than IR methylphenidate 25mg three times daily (66.0±17.4ng·h/mL), confirming steady-state levels during the study period. All treatment regimens were safe and well tolerated. MPH-MLR 80-mg capsule once daily or IR methylphenidate 25mg three times daily provides comparable maximum methylphenidate concentrations and systemic exposure in the fed state.

Study of the physical properties of calcium alginate hydrogel beads containing vineyard pruning waste for dye removal

In this work the morphological and surface properties of a biocomposite formulated with vineyard pruning waste entrapped in calcium alginate hydrogel beads were studied. The formulation of the calcium alginate hydrogel beads, containing vineyard pruning waste, was based on the capacity of this green adsorbent to remove dye compounds from wastewater, observing that in the optimum condition (1.25% of cellulosic residue, 2.2% of sodium alginate and 0.475molL−1 CaCl2) the percentage of dyes was reduced up to 74.6%. At lower concentration of CaCl2, high-resolution optical images show that the elongation of the vineyard-alginate biocomposite decreased, whereas the compactness increased. Moreover, higher concentrations of cellulosic residue increased the biocomposite roundness in comparison with biocomposite without the cellulosic residue. Interferometric perfilometry analysis (Ra, Rq, Rz and Rt) revealed that high concentrations of CaCl2 increased the roughness of the of the calcium alginate hydrogel beads observing vesicles in the external surface.

Formulation and In vitro Characterization of Floating Gel Beads of Metformin Hydrochloride

A floating type dosage form, gel beads of metformin hydrochloride was prepared by emulsification gelation technique. The gel bead was formed by mixing the polymer in water, oil phase and it was extruded in the calcium chloride solution as curing agent. The formulation parameters optimized were polymer ratio, concentration of oil, curing time on drug content, floating lag time, morphology, swelling of beads and release kinetics.The scanning electron photomicrographs revealed morphology of beads. The size of beads was measured. Entrapment efficiency of drug loaded beads was found to be over 90%. In vitro release of metformin hydrochloride from alginate–pectin beads into simulated gastric fluid at 37 ºC showed no significant burst effect. The cumulative release reached above 74.71 ± 4.15% in about 12h. The use of sodium alginate and combinations of sodium alginate with pectin were used to study the effect on the sustained release of the drug from the formed beads. It was found that sodium alginate was not sufficient to sustain the drug release at gastric pH (fed condition). Appropriate combination of alginate and pectin could provide the sustained release of drug. Floating gel beads formulation provides an alternative delivery for metformin in diabetes treatment.

Effect of Alginate and Surfactant on Physical Properties of Oil Entrapped Alginate Bead Formulation of Curcumin

Effect of Alginate and Surfactant on Physical Properties of Oil Entrapped Alginate Bead Formulation of Curcumin

On the encapsulation of natural pesticide using polyvinyl alcohol/alginate–montmorillonite nanocomposite for controlled release application

A representative pesticide, NeemAzal was encapsulated into polyvinyl alcohol/alginate‐montmorillonite (PVA/Alg‐MMT) nanocomposite by cross‐linking with glutaraldehyde. Different formulations of capsule beads containing NeemAzal were prepared with different concentration of materials. Evidence of cross‐linking of PVA and Alg was obtained by comparison of the Fourier transform infrared spectra of the initial substrates and capsule beads. X‐ray diffraction and transmission electron microscopy techniques confirmed the intercalated structure of capsule bead nanocomposites. In addition the swelling behavior of capsule beads was investigated. Results showed that swelling ratio of capsule beads decreases with introduction of MMT as well as increase of PVA content in capsule bead formulations. The release characteristics of NeemAzal from capsule beads were monitored using UV–visible spectrophotometer in distilled water. The addition of sodium MMT to these formulations was found to have a profound inhibitory effect on the release of NeemAzal. Furthermore, the release data were fitted to several empirical equations to estimate the kinetic parameters. The NeemAzal encapsulated PVA/Alg‐MMT nanocomposite capsule beads, designed and discussed in this work, have the potential for controlled release of pesticide. POLYM. ENG. SCI., 54:2707–2714, 2014. © 2013 Society of Plastics Engineers

Formulation and Development of Diltiazem Hydrochloride Sustained Release Alginate Beads by Ionotropic External Gelation Technique

Background of the research: Diltiazem HCL (DTZ), has short biological half life of 3-4 h, requires rather high frequency of administration.Due to repeated administration there may be a chances of patient incompliance and toxicity problems. Objective: The objective of study was to develop sustained release alginate beads of DTZ for reduction in dosing frequency, high bioavailability & better patient compliance. Methodology: Alginate beads were prepared by ionotropic external gelation technique using CaCl2 as cross linking agent. Prepared beads were evaluated for % yield, encapsulation efficiency, swelling index in 0.1N HCL and 7.4 phosphate buffer, drug release study, FT-IR, FE-SEM analysis. In order to improve %EE and drug release, pectin, methyl cellulose and locust bean gum were used as co-polymers along with sodium alginate. Result: Yield was found to be in the range of 72.41-96.43. % EE was 47.3% (F1), 71.1% (F5). In pH 7.4, beads showed increase in swelling index as compare to in 0.1 N HCL. Among use of different copolymers, locust bean gum sustained the DTZ release up to 55.98% (F6) in 12 hrs. FT-IR analysis revealed no drug excipient interference. Prepared beads were found to be rough, with cracks and pores on the surface. Conclusion: It was concluded that DTZ could be successfully entrapped and sustained in sodium alginate beads with use of locust bean gum.

Effect of Alginate and Surfactant on Physical Properties of Oil Entrapped Alginate Bead Formulation of Curcumin

Effect of Alginate and Surfactant on Physical Properties of Oil Entrapped Alginate Bead Formulation of Curcumin