Controlled Release Formulations Research Articles

Synthesis of tapioca starch/palm oil encapsulated urea-impregnated biochar derived from peppercorn waste as a sustainable controlled-release fertilizer

Nutrient leaching and volatilization cause environmental pollution, thus the pursuit of developing controlled-release fertilizer formulation is necessary. Biochar-based fertilizer exhibits slow-release characteristic, however the nutrient release mechanism needs to be improved. To overcome this limitation, the approach of applying encapsulation technology with biochar-based fertilizer has been implemented in this study. Black peppercorn waste was used to synthesize urea-impregnated biochar (UIB). Central composite design was used to investigate the effects of pyrolysis temperature, residence time and urea:biochar ratio on nitrogen content of UIB. The optimum condition to synthesize UIB was at 400 °C pyrolysis temperature, 120 min residence time and 0.6:1 urea:biochar ratio, which resulted in 16.07% nitrogen content. The tapioca starch/palm oil (PO) biofilm formulated using 8 g of tapioca starch and 0.12 µL of PO was coated on the UIB to produce encapsulated urea-impregnated biochar (EUIB). The UIB and EUIB pellets achieved complete release of nitrogen in water after 90 min and 330 min, respectively. The nutrient release mechanism of UIB and EUIB was best described by the Higuchi model and Korsmeyer-Peppas model, respectively. The improvement of water retention ratio of UIB and EUIB pellets was more significant in sandy-textural soil as compared to clayey-textural soil. The EUIB derived from peppercorn waste has the potential to be utilized as a sustainable controlled-release fertilizer for agriculture.

Scale-up in twin-screw wet granulation: impact of formulation properties

The focus of this study was to investigate the sensitivity of different drug formulations to differences in process parameters based on previously developed scale-up strategies. Three different formulations were used for scale-up experiments from a QbCon® 1 with a screw diameter of 16 mm and a throughput of 2 kg/h to a QbCon® 25 line with a screw diameter of 25 mm and a throughput of 25 kg/h. Two of those formulations were similar in their composition of excipients but had a different API added to the blend to investigate the effect of solubility of the API during twin-screw wet granulation, while the third formulation was based on a controlled release formulation with different excipients and a high fraction of HPMC. The L/S-ratio had to be set specifically for each formulation as depending on the binder and the overall composition the blends varied significantly in their response to water addition and their overall granulation behavior. Before milling there were large differences in granule size distributions based on scale (Earth Mover’s Distance 140–1100 µm, higher values indicating low similarity) for all formulations. However, no major differences in granule properties (e.g. Earth Mover’s Distance for GSDs: 23–88 µm) or tablet tensile strength (> 1.8 MPa at a compaction pressure of 200 MPa for all formulations with a coefficient of variation < 0.1, indicating high robustness for all formulations) were observed after milling, which allowed for a successful scale-up independent of the selected formulations.

Design of innovative agrochemical delivery system for sustainable agriculture and to alleviate environmental and health hazards

This article deals with formation of hydrogels encapsulated with agrochemicals for minimizing agrochemical-environmental pollution and health hazards. These copolymers as controlled release formulations (CRF) were designed by grafting reaction onto natural polymers starch-agar-gelatin and poly(2-acrylamido-2-methylpropanesulphonic acid) (AMPS). Copolymers were characterized by SEM, AFM, and XRD along with FTIR and 13C NMR techniques. SEM and AFM confirmed the un-even morphology with surface roughness and XRD indicated the amorphous nature of the polymers after grafting. Controlled diffusion of thiophante methyl fungicide for 72 h occurred with diffusion non-Fickian type. It is useful observation for preventing leaching and evaporation loss of fungicide and to alleviate environmental and health hazards. After degradation CRF may improve micronutrients and soil quality.

Oral Drug Delivery Systems Applied to Launched Products: Value for the Patients and Industrial Considerations.

Drug delivery systems (DDS) control the amount, rate, and site of administration of drug substances in the body as well as their release and ADME (absorption, distribution, metabolism, excretion). Among the various types of DDS, amount-controlled DDS for solubilization and absorption increase the bioavailability. Time- and amount-controlled DDS are controlled release formulations classified as (1) membrane-type, (2) matrix-type, (3) osmotic-type, and (4) ion-exchange type. Timed-release formulations also control the time and amount of release and the absorption of drugs. Site- and amount-controlled DDS are characterized by colonic delivery and intestinal lymph-targeting to improve release and ADME of drug substances. Finally, site-, time-, and amount-controlled DDS are gastroretentive formulations and local delivery in the oral cavity to improve site retention, release, and ADME of drugs. DDS can enhance efficacy, reduce adverse effects, and optimize the dosing frequency of various drug products to increase patient value. This review focuses on patient value and industrial considerations of launched oral DDS. We provide a technological overview of candidate and marketed DDS, as well as the pros/cons of the technologies for industrialization with consideration to excipients, manufacturing, and storage stability. Moreover, to demonstrate the usefulness of the technology and support the selection and development of the best technologies for patients, we also describe patient value from clinical studies and analyses, particularly with regard to increased new medical options, higher efficacy, reduced adverse effects, reduced number of doses and clinic visits, easier administration, higher quality of life, greater adherence, and satisfaction.

Chitosan-Delivered Chlorantraniliprole for Pest Control: Preparation Optimization, Deposition Behavior, and Application Potential.

Chitosan has emerged as a promising biopolymer carrier for the sustained release of pesticides owing to its good biocompatibility, biodegradability, and bioactivity. In this work, a controlled-release formulation of insecticide chlorantraniliprole was fabricated through coprecipitation-based synchronous encapsulation with chitosan, where the optimum preparation conditions, storage stability, deposition behavior, and application potential were investigated. Preparation of optimization data from response surface methodology showed high correlation coefficient (R2) of 0.9875 and adjusted coefficient (Radj2) of 0.9715. The resulting formulation displayed good loading content of 28.39%, high encapsulation efficiency of 75.71%, and good storage stability. Compared with the commercial suspension concentrate, the formulation exhibited better wettability and retention behaviors on plant leaves. Excitingly, effective control against one species of mealybug genus Paraputo Laing (outside the killing spectrum) on the Hippeastrum reticulatum plant was successfully achieved by spraying the controlled-release formulation at different time intervals. This work indicates the good potential of the developed formulation in expanding the application scope of chlorantraniliprole, which shows a new strategy for sustainable pest management.

Model-based optimization of controlled release formulation of levodopa for Parkinson’s disease

Levodopa is currently the standard of care treatment for Parkinson’s disease, but chronic therapy has been linked to motor complications. Designing a controlled release formulation (CRF) that maintains sustained and constant blood concentrations may reduce these complications. Still, it is challenging due to levodopa’s pharmacokinetic properties and the notion that it is absorbed only in the upper small intestine (i.e., exhibits an “absorption window”). We created and validated a physiologically based mathematical model to aid the development of such a formulation. Analysis of experimental results using the model revealed that levodopa is well absorbed throughout the entire small intestine (i.e., no “absorption window”) and that levodopa in the stomach causes fluctuations during the first 3 h after administration. Based on these insights, we developed guidelines for an improved CRF for various stages of Parkinson’s disease. Such a formulation is expected to produce steady concentrations and prolong therapeutic duration compared to a common CRF with a smaller dose per day and a lower overall dose of levodopa, thereby improving patient compliance with the dosage regime.

Sodium alginate-carboxymethyl chitosan hydrogels loaded with difenoconazole for pH-responsive release to control wheat crown rot

Increasing concern about environmental pollution has driven the development of controlled release formulations for agrochemicals. Due to the advantages of degradability and responsiveness to environmental stimuli, polysaccharide-based hydrogel is an ideal carrier for agrochemicals controlled release. In this study, a method-easy polysaccharide hydrogel for controlled release of difenoconazole (DZ) was prepared with sodium alginate (SA) and carboxymethyl chitosan (CMCS). Due to its three-dimensional crosslinked mesh structure, the prepared hydrogels (CSDZ) showed an agrochemical load capacity of 9.03 % and an encapsulation efficiency of 68.64 %. The release rate is faster in alkaline solution, followed by neutral solution, and slowest in an acid environment, which is consistent with the swelling behavior. Furthermore, leaching studies showed that CSDZ hydrogels have excellent protective properties for encapsulated agrochemicals. Compared with technical DZ, the results of in vitro and pot antifungal testing showed that CSDZ had a better control effect against wheat crown rot (Fusarium pseudograminearum). Safety assessment studies indicated that CSDZ hydrogels exhibit good biocompatibility on nontargeted organisms (Daphnia magna, zebrafish and Eisenia fetida) and wheat. This study aims to provide a potentially promising approach for the preparation and application of biocompatible polysaccharide-based hydrogels for agrochemical-controlled release in sustainable disease management.

The forgotten material: Highly dispersible and swellable gelatin-based microspheres for pulmonary drug delivery of cromolyn sodium and ipratropium bromide

Controlled-release formulations for pulmonary delivery are highly desirable for treating chronic diseases such as COPD. However, a limited number of polymers are currently approved for inhalation. The study presents a promising strategy using gelatin as a matrix for inhalable dry powders, allowing the controlled release of ionic drugs. Ionized cromoglicate sodium (CS) and ipratropium bromide (IBr) interacted in solution with charged gelatin before spray drying (SD). Calcium carbonate was used as a crosslinker. The microspheres showed remarkable aerosol performance after optimizing the SD parameters and did not cause cytotoxicity in A549 cells. The microspheres were highly dispersible with ∼ 50–60% of respirable fraction and fine particle fraction 55–70%. Uncrosslinked microspheres increased their size from four to ten times by swelling after 5 min showing potential as a strategy to avoid macrophage clearance and prolong the therapeutic effect of the drug. Crosslinkers prevented particle swelling. Ionic interaction generated a moderate reduction of the drug release. Overall, this study provides a novel approach for developing DPI formulations for treating chronic respiratory diseases using a biopolymer approved by the FDA, potentially enhancing drug activity through controlled release and avoiding macrophage clearance.

Crystal structure determination and DFT analysis of doxorubicin hydrochloride for controlled-release drug formulations

Doxorubicin hydrochloride (DOX) is a widely used chemotherapeutic drug that inhibits the growth of cancer cells. Many DOX-based controlled-release systems have been proposed to reduce toxicity. However, knowledge of its crystal structure is essential for optimizing drug release processes and designing co-crystals or salts with different release properties. Although DOX has been extensively studied, no crystal structure is available in the Cambridge Structural Database or literature. In this work, we determine the crystal structure of DOX using a simulated annealing approach based on powder X-ray diffraction data. We confirm its validation by Rietveld refinement and molecular cohesion by using a molecular geometry check tool. We also use density functional theory to optimize the DOX structure and obtain the minimum energy conformation, H-bond donor/acceptor species, charge localization, and crystal structure parameters. This study provides essential structural information on DOX that can be used to rationalize new modified-release dosage forms and to design co-crystals or salts with different release properties.

Food-grade polymers: A new vision in the controlled release of bioactive substances

Food-grade polymers are largely employed in food industry for a variety of purposes, including food preservation, texture modification and food packaging. They are considered safe for human consumption and are approved by regulatory bodies such as the FDA and EFSA. One of the most common uses of food-grade polymers is in food packaging. They are used to create packaging materials that are resistant to moisture, oxygen and to prevent contamination. Food- grade polymers are also used in the formulation of dietary supplements, fortified foods, and modified-release pharmaceuticals. They help improve the stability, shelf life and bioavailability of active ingredients. For example, specific polymers can be tailored to create controlled-release formulations, in which the active ingredient is released gradually over time, resulting in a more consistent and prolonged effect. In addition, food-grade polymers can be used to improve the texture and appearance of dietary supplements and oral pharmaceutical forms, mask unpleasant tastes and odors and making them more palatable to consumers. This paper overviews the application of food-grade polymers in the preparation of modified and targeted delivery systems for drugs and nutraceutical ingredients.

Optimization of Self-Double Emulsifying Drug Delivery System Using Design of Experiments for Enhanced Oral Bioavailability of Gentamicin: In-vitro, Ex-vivo and In-vivo Studies

Water-in-oil-in-water (w/o/w) double emulsions have shown excellent capability in augmenting the enteral bioavailability of BCS class III drugs, besides being effective controlled-release formulations. However, the problem of thermodynamic instability has restrained their industrial applicability. The self-double emulsifying drug delivery system (SDEDDS) is one of several approaches used to improve the stability of double emulsions. SDEDDS is a mixture of primary emulsion and secondary surfactant that can spontaneously emulsify into double emulsions in an external aqueous environment with mild agitation. Here, we prepared SDEDDS of gentamicin sulfate by response surface methodology. Selected optimized formulations (ODS1 and ODS2) were evaluated for zeta potential (Y1), optical clarity (Y2), release at 420 min (Y3), emulsion stability index (Y4) and self-emulsification time (Y5). For ODS1, Y1=−35.45 (±1.06)mV, Y2=53.19 (±0.35)%, Y3=75.79 (±0.60)%, Y4=93.97(±0.15)% and Y5=0.631 (±0.014)min, whereas for ODS2, Y1=−35.70 (±0.56)mV, Y2=48.09 (±0.64)%, Y3=76.61 (±0.99)%, Y4=93.00(±0.94)% and Y5=0.687(±0.02)min. Furthermore, ex-vivo studies on intestinal permeability revealed that SDEDDS improved membrane permeability compared to drug solution. Histopathology investigations revealed that SDEDDS promoted permeation without causing significant local membrane distortion. In addition, in-vivo studies revealed a 2.84 -fold increase in AUC0-∞ of optimized SDEDD compared to pure drug oral solution.

Formulation and evaluation of controlled-release, carrageenan-based powder formulations filled into hard gelatin capsules

Hard gelatin capsules (HGCs) are typically used as immediate release dosage forms, however, controlled drug release can from HGCs be obtained by the application of film coating onto the capsule shells or by filling them with controlled release multi-particulates (e.g. pellets and mini-tablets).&#x0D; The filling of a hydrophilic gelling polymer into the capsule is an alternative approach to the time-consuming preparation and filling of multi-particulates. Carrageenan is a linear, sulfated polysaccharide that is commonly used as a thickener in pharmaceutical formulations.&#x0D; The release behavior of propranolol HCl – carrageenan powder mixtures filled into hard gelatin capsules was investigated as a function of drug – to – polymer ratio, the capsule fill weight, grade of carrageenan used. In addition, the effect of the drug release testing method (USP apparatus I or II), rotation speed, pH of the release medium and ionic strength of the release medium on drug release were investigated.&#x0D; The electrostatic interaction of propranolol HCl with carrageenan was also investigated using equilibrium dialysis method to determine the binding capacity and the stability constant of the complex formed.&#x0D; Viscarin GP 109 was found to provide a fast-gelling behavior with excellent controlled release properties. Drug loading and ionic strength of the medium significantly influenced drug release. Release in USP apparatus 1 was slower than that in USP apparatus 2. Propranolol HCl formed an insoluble complex with carrageenan with a high binding capacity and stability

Cyclodextrin based Nanosponges for the Oral Delivery of Actarit: Physicochemical Characterisation and Dissolution Studies

Introduction: The current research aims to formulate a controlled release formulation of Actarit utilizing cyclodextrin based nanosponges as a nanocarriers. β-Cyclodextrin built nanosponges were prepared by condensation reaction using diphenyl carbonate as crosslinking agent. Method: A 3-level, 3-factor Box-Behnken design was used to optimize the reaction conditions. The particle size, zeta potential and solubilization efficiency of prepared nanosponges were determined. Actarit was loaded into nanosponges by freeze drying method. Actarit loaded nanosponges were further evaluated for particle size, zeta potential, surface morphology, FTIR, DSC, XRD and Dissolution characteristics. The cyclodextrin nanosponges prepared under optimum conditions exhibited a particle size range of 143.42 to 152.76 nm with low polydispersity indices. FTIR spectra confirmed the formation of carbonyl bond between the β-Cyclodextrin molecules. Results and Discussion: Actarit loaded nanosponges exhibited a particle size range of 157.13 to 168.34 nm with minimum polydispersity index. The zeta potential value was sufficiently high to maintain the stability of colloidal nanosponges. TEM image exposed the spherical structure of drug loaded nanosponges that could be retained and released gradually over time. The FTIR, DSC and XRPD studies inveterate the interaction between Actarit and nanosponges. The drug loaded nanosponges displayed a significant progress in dissolution of drug when compared to plain Actarit. The initial rapid release of Actarit from nanosponges formulations was observed. After 24 h of study, around 90 % of the drug released from nanoformulation and only around 20 % of the drug from free drug suspension. Conclusion: Cyclodextrin based nanosponges displayed superior complexing capability with increased solubility of poorly soluble Actarit.

Investigation of herbicide sorption-desorption using pristine and organoclays to explore the potential carriers for controlled release formulation

Injudicious application of available commercial herbicide formulations leads to water, air and soil contamination, which adversely affect the environment, ecosystems and living organisms. Controlled release formulation (CRFs) could be an effective way to reduce the problems associated with commercially available herbicides. Organo-montmorillonites are prominent carrier materials for synthesising CRFs of commercial herbicides. Quaternary amine and organosilane functionalised organo-montmorillonite and pristine montmorillonite were used to investigate their potential as suitable carriers for CRFs in herbicide delivery systems. The experiment involved a batch adsorption process with successive dilution method. Results revealed that pristine montmorillonite is not a suitable carrier for CRFs of 2,4-D due to its low adsorption capacity and hydrophilic nature. Conversely, octadecylamine (ODA) and ODA-aminopropyltriethoxysilane (APTES) functionalised montmorillonite has better adsorption capacities. Adsorption of 2,4-D onto both organoclays is higher at pH.3 (232.58% for MMT1 and 161.29% for MMT2) compared to higher pH until pH.7 (49.75% for MMT1 and 68.49% for MMT2). Integrated structural characterisation studies confirmed the presence of 2,4-D on the layered organoclays. The Freundlich adsorption isotherm model fitted best to the experimental data, which revealed an energetically heterogeneous surface of the experimental organoclays, and adsorption which specifically involved chemisorption. The cumulative desorption percentages of adsorbed 2,4-D from MMT1(2,4-D loaded) and MMT2(2,4-D loaded) after seven desorption cycles were 65.53% and 51.45%, respectively. This outcome indicates: firstly, both organoclays are potential carrier materials for CRFs of 2,4-D; secondly, they have the ability to reduce the instantaneous release of 2,4-D immediately after application; and thirdly, eco-toxicity is greatly diminished.

Design and In-vivo Evaluation of Quercetin Nanosponges-based Buccal Tablets of Quercetin

The objective was to increase the bioavailability of quercetin by creating a controlled release formulation using nanosponges based on cyclodextrin. Based on the early testing, a 3-factor, 3-level Box-Behnken design with quercetin was loaded into nanosponges using the freeze-drying process. The prepared nanosponges were examined after being described and made into tablets. The quercetin-loaded nanosponges have particle sizes ranging from 36.45 to 135.27 nm, encapsulation efficiencies ranging from 42.37 to 88.44%, and drug release percentages at 6 hours ranging from 53.04 to 82.64%. The FTIR, DSC, and XRD investigations validated the Quercetin interaction with nanosponges. The medicine released from the nanosponges buccal tablets in-vitro at a rate of 99.75%, and stability testing showed no significant changes within six months after the nanosponges were transformed into tablets. In-vivo studies in rats showed that quercetin optimised nanosponges tablets Cmax of 6.27 ± 0.06 ng/mL was significantly higher (p

Polysaccharide-Based Formulations for the Treatment of Diabetic Wounds: A Review

This article highlights recent progress in the development of polysaccharide-based formulations for the treatment of diabetic wounds. Wound healing is generally slower in diabetic patients than in non-diabetic individuals, which can be complicated into cellulitis, gangrene and foot abscess. Here, the influence of diabetes on the wound healing process and the potential effects of polysaccharide-based formulations on wounds associated with diabetes mellitus are described. Polysaccharides are excellent candidates for effective skin repair due to the characteristics of biodegradability, biocompatibility, and non-toxicity. Common polysaccharides employed in the development of diabetic wound care include cellulose, hyaluronic acid, and alginate. In addition, novel polysaccharides for diabetic wound care have been extracted from natural materials used for traditional medicine, such as Ganoderma lucidum, Periplaneta americana, and psyllium seed husk. Several strategies have been adopted, including crosslinking, grafting, quaternation, nanoformulation, and polymeric composites, to improve the physicochemical and mechanical attributes of polysaccharide-based formulations. These properties are crucial to the wound healing process by facilitating wound closure via accelerated re-epithelialization and collagen synthesis, as well as maintaining an optimal moist environment while minimizing the risk of infection and scar formation. The roles of stimuli-responsive polymers, controlled-release formulations, and bioactive polysaccharides in facilitating diabetic wound healing are also discussed.

Physicochemical and Pharmacokinetic Studies of Metformin for Development of Controlled Release Matrix Tablet: Formulation Optimization Using in silico Tools

Metformin, taken by nearly 120 million people across the world as a treatment for type 2 diabetes, has a relatively short plasma half-life and low absolute bioavailability. In this study, physicochemical and pharmacokinetics properties of metformin have been thoroughly assayed using ADMETLab, SwissADME, SmartCYP, LigandScout web-servers and software to evaluate the effectiveness of its formulation as controlledrelease matrix tablets. The objective of the present work was to develop a formulation of an oral controlled-release (CR) metformin tablet, using hydrophilic hydroxylpropylmethylcellulose (HPMC) grades K4M and K100M polymers at different concentrations utilizing computational simulatory tools. Intestinal membrane permeability of the drug has been assayed using 2 hours simulation run with MembranePlus Software. Simulated environment generated for in silico dissolution study, using DDDPlus software, of the prepared formulations used USP Apparatus Type 2 rotating at 100 rpm. The simulation run was for 2 hours using 0.1N HCl phase followed by 8 hours with 6.8 USP Phosphate buffer phase. The results showed that drug release from the higher viscosity grade, K100M was slower as compared to the lower viscosity grade K4M at a fixed polymer concentration level. Furthermore, plasma concentration-time curves for the formulations have been generated using GastroPlus software. Dhaka Univ. J. Pharm. Sci. 22(1): 29-42, 2023 (June)

Recent Approaches of Matrix Release Tablet in NDDS System

The purpose of this analysis is to categorize matrix tablets according to the kind of polymer they are made of as well as the rate at which they release their contents. When it came to medicinal applications, the matrix system was the very first oral extended release platform ever developed. The utilization of matrix tablets enables the modification of drug release characteristics. They are highly favored for this kind of treatment because of the benefits they give for the patient in terms of better adherence to the treatment, more stable medication levels, decreased dose and bad effects, and a bigger safety margin for highly potent medications. Because of their versatility in delivering a desired drug release profile, cheap cost, and general regulatory acceptability, hydrophilic polymer matrix systems are frequently used in oral controlled drug delivery dosage forms. Because of the rapid diffusion of the dissolved medication via the hydrophilic gel network, the use of hydrophilic matrix alone for delayed drug release is not possible for medicines that are very water soluble. It is now generally accepted that the formulation of such drugs requires the use of matrix systems that incorporate hydrophobic polymers. It would appear that the most successful strategy would be to create a formulation for oral controlled release by employing matrix tablets.

Investigation of the physicochemical properties of amine-modified organoclays influenced by system pH and their potential to adsorb anionic herbicide

Organically modified montmorillonites have already attracted the attention of researchers due to their eco-friendly characteristics and versatile application in our daily lives. Their application is now being widely explored as a potential carrier for preparing solid-laden controlled release formulations (CRFs) of herbicides. The suitability of a new formulation mainly depends on herbicide releasing behaviour under various conditions, which is governed by the interaction mechanisms between carrier materials and target herbicide. The physicochemical properties of carriers and herbicides are the key components for establishing the probable interaction mechanisms between them. The physicochemical properties of amine-modified organoclays are mostly pH dependent and this experiment investigated the effect of pH on surface chemistry and how it changes when system pH is varied. Results revealed that the organoclays converted from protonated to deprotonated conditions as well as from hydrophobic to hydrophilic states with increasing system pH, from acidic to alkaline conditions. The release of surfactants from the organoclays was higher in acidic and alkaline pH conditions than in neutral pH. The release of major structural elements was highest in acidic conditions, but gradually abated with increasing system pH until neutral conditions were achieved. After that they increased slightly to an alkaline state, except for iron (Fe). Zeta values of both organoclays gradually diminished as system pH increased. The surface area of organoclays was highest at neutral pH, and gradually waned towards acidic and alkaline pH. This ultimately affects adsorption of anionic herbicide onto the various pH-adjusted organoclays. The adsorption was highest at around the pKa value of the herbicide and gradually declined with increasing system pH to a neutral state, and then slightly increased towards a higher pH. Based on this, it can be concluded that system pH exerts a significant influence on the physicochemical properties of amine-modified organoclays. This may affect firstly, adsorption of pesticides onto the interlayer gallery of the organoclays for CRFs of pesticides; and secondly, the formulation’s releasing behaviour and ultimate efficacy of the synthesised formulation.

Biodegradative controlled natural toxin release from Pimelea trichostachya-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) biocomposites: Towards a sustainable intra-ruminal device

To address the need to develop rumino-reticulum devices (RRDs) for prolonged delivery of natural toxins that can protect Australian cattle from the fatal Pimelea poisoning by stimulating their own detoxification capability, a range of melt-extruded biocomposites were prepared from two formats of Pimelea plant materials (these being ground Pimelea plant particles and their derived ethanol extracts) combined with the biodegradable biopolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). To explore the close to end-of-life biodegradation and natural toxin release behaviors of these materials in the rumen environment, they were incubated for less than 29 days in anaerobic and aqueous sewage sludge using the mesophilic biochemical methane production (BMP) assay. Characterization of the composites over time (and thus over different degrees of biodegradation) using X-ray computed tomography scanning (μ-CT), differential scanning calorimetry (DSC), size exclusion chromatography (SEC), and quantification of the residual polymer contents by weight, confirmed that there was a consistent surface biodegradation mechanism. The biodegradation kinetics were well simulated using a parallel-mass-loss model combined with an adapted Gompertz model, confirming that initial microorganism growth in biofilm formation/biomass adaptation is the rate-limiting step. The natural toxin release kinetics were obtained by determining the concentrations of the principal natural toxin, simplexin, in the biocomposites before and after biodegradation using an optimized analytical methodology based on ultra-high performance liquid chromatography hyphenated with a quadrupole Orbitrap mass spectrometry (UHPLC-Q-Orbitrap-MS). These release kinetics were appropriately described by a new model that considered the interplay of burst release, toxin adsorption, and biodegradation. These findings will not only aid the future RRD design by identifying that the Pimelea plant extracts are preferred as the toxin source, but also extend the understanding of the anaerobic biodegradation of PHBV-based biocomposites and highlight the need to consider toxin sorption effects in controlled release formulations.