Controlled Release Products Research Articles

Nanopesticides in comparison with agrochemicals: Outlook and future prospects for sustainable agriculture

Agrochemicals are products of advanced technologies that use inorganic pesticides and fertilizers. Widespread use of these compounds has adverse environmental effects, leading to acute and chronic exposure. Globally, scientists are adopting numerous green technologies to ensure a healthy and safe food supply and a livelihood for everyone. Nanotechnologies significantly impact all aspects of human activity, including agriculture, even if synthesizing certain nanomaterials is not environmentally friendly. Numerous nanomaterials may therefore make it easier to create natural insecticides, which are more effective and environmentally friendly. Nanoformulations can improve efficacy, reduce effective doses, and extend shelf life, while controlled-release products can improve the delivery of pesticides. Nanotechnology platforms enhance the bioavailability of conventional pesticides by changing kinetics, mechanisms, and pathways. This allows them to bypass biological and other undesirable resistance mechanisms, increasing their efficacy. The development of nanomaterials is expected to lead to a new generation of pesticides that are more effective and safer for life, humans, and the environment. This article aims to express at how nanopesticides are being used in crop protection now and in the future. This review aims to shed some light on the various impacts of agrochemicals, their benefits, and the function of nanopesticide formulations in agriculture.

Formulation, evaluation, and optimization of the omeprazole magnesium multi-unit particulate controlled release tablets using different concentrations of polymers

Multi-Unit Particulates (MUPs) with matrix pellets are used to develop controlled release products of various active pharmaceutical ingredients. They may allow improvement in solubility and thereby bioavailability of poorly soluble drugs. Omeprazole magnesium is a derivative of benzimidazole which belongs to the group of proton pump inhibitors that exhibits degradation in gastric acid with short biological life and variability in bioavailability. The drug degradation problem was overcome by the coating of pellets with enteric coating agents which disperse in the gastrointestinal tract more homogenously than single units with a rapid transit time. Pellets were compressed to reduce the tampering risk and transportation difficulty through the esophagus. The coating was done with the bottom spray technique. A batch of 5% concentration of binder optimized for a tablet affects the disintegration of the tablet. A cushioning agent was employed to optimize the acid resistance with a concentration of 12% and the release profile was depicted in pH 6.8 phosphate buffer followed by 0.1N HCl for 2 hours. The optimized batch was evaluated for acid resistance, similarity factor, SEM, dissolution, and stability studies which exhibited maximum resistance in gastric pH with abrupt release in duodenal pH because of the multi-particulate approach.

Evaluation on the Activity and Efficacy of Omniprene™ WSP and XWSP Against the Southern House Mosquito Culex quinquefasciatus in Simulated Catch Basins.

Mosquitoes and mosquito-borne diseases remain one of the major public health burdens. In most cases, vector control is the main or the only intervention to mitigate these problems. We are facing the challenges of traditional, emerging, or resurging vectors and diseases, yet the availability and affordability of safe and effective mosquito control products are at a historical low. Development of new active ingredients (AI) and novel formulations based on currently available AI are demanded by mosquito control operations. This paper validated the bioactivity in the laboratory and evaluated the semi-field efficacy for 2 newly registered controlled-release products based on juvenile hormone analog S-methoprene: OmniPrene™ water-soluble pouch (WSP) and extended water-soluble pouch (XWSP). Along with technical S-methoprene, these 2 formulations showed high inhibition of adult emergence in laboratory bioassays against Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus that are commonly found in catch basins. High initial and long-term residual efficacy were demonstrated in simulated catch basins against Cx. quinquefasciatus, where the OmniPrene WSP consistently provided over 90% control for 15 wk (105 days) and OmniPrene XWSP did the same for 38 wk (266 days). Considering the need for reliable mosquito control products, combined with commonly encountered product performance issues in catch basins, OmniPrene WSP and XWSP can be viable tools to combat mosquito species of public health concern that are associated with urban drainage systems.

A REVIEW ON HOW TO CHARACTERIZE AND EVALUATE THE OPHTHALMIC IN SITU GEL PREPARATIONS

In situ gelling systems are becoming one of the most popular and well-known, with many potential benefits from delivery systems, such as ease of use and ease of manufacture, improve adherence and patient comfort by minimizing the frequency of drug administration. In this review, we will describe the characterization and evaluation of the ophthalmic in situ gel preparation. Among them are physical evaluation (appearance and clarity, pH, isotonicity, gelation temperature, gelling capacity, viscosity, and stability), chemical evaluation (determining drug content, drug release), microbiological evaluation (sterility, ocular irritability, ocular tolerability, antimicrobial activity, hemolysis activity, bovine corneal opacity and permeability (BCOP) test, preservative efficacy test (PET), microtetrazolium (MTT) reduction cytotoxicity test), and in vivo evaluation such as pharmacokinetic and pharmacodynamic evaluation. Characterizing the chemical, physical, microbiological, and miscellaneous properties of ophthalmic in situ gel formulations can meet the ideal requirements and help determine the best formulation of ophthalmic in situ gel to achieve higher bioavailability values, longer contact times, minimize side effects, not causing irritation or liquid tear production, and providing a maximum therapeutic effect. In situ gels offer the primary requirement of a successful controlled release product that is increasing patient compliance.

Gastroretentive Technologies in Tandem with Controlled-Release Strategies: A Potent Answer to Oral Drug Bioavailability and Patient Compliance Implications.

There have been many efforts to improve oral drug bioavailability and therapeutic efficacy and patient compliance. A variety of controlled-release oral delivery systems have been developed to meet these needs. Gastroretentive drug delivery technologies have the potential to achieve retention of the dosage form in the upper gastrointestinal tract (GIT) that can be sufficient to ensure complete solubilisation of the drugs in the stomach fluids, followed by subsequent absorption in the stomach or proximal small intestine. This can be beneficial for drugs that have an “absorption window” or are absorbed to a different extent in various segments of the GIT. Therefore, gastroretentive technologies in tandem with controlled-release strategies could enhance both the therapeutic efficacy of many drugs and improve patient compliance through a reduction in dosing frequency. The paper reviews different gastroretentive drug delivery technologies and controlled-release strategies that can be combined and summarises examples of formulations currently in clinical development and commercially available gastroretentive controlled-release products. The different parameters that need to be considered and monitored during formulation development for these pharmaceutical applications are highlighted.

Floating chitosan-alginate microspheres loaded with chlorantraniliprole effectively control Chilo suppressalis (Walker) and Sesamia inferens (Walker) in rice fields

Striped rice stem borer, Chilo suppressalis (Walker) and pink stem borer, Sesamia inferens (Walker) are two important pests, causing substantial yield loss in rice production. Application of conventional synthetic pesticides, such as suspension concentrates and water-dispersible granules, is a primary method for control of the two pests. Due to the flow of water in rice field, spray drift, and soil adsorption, applied such pesticides are often out of the target, resulting in low control efficacy, potential contamination of soil or surface water, and also threat to human health. Thus, there is an urgent need for developing environmentally friendly and highly targeted pesticide formulations to meet the challenges. The present study synthesized chlorantraniliprole loaded chitosan-alginate floating hydrogel microspheres (CCAM) through physical embedding, ionic crosslinking, and incorporation of citronellol as an oil phase. The morphology, particle size, entrapment efficiency, loading capacity, in vitro slow-release kinetics, and floating ability of the CCAM were tested in laboratory conditions. The CCAM and two commercial formulations (suspended and granulated) of chlorantraniliprole were respectively evaluated in two rice fields located in two provinces of China. The CCAM was able to float on the surface of rice field, gather around rice stems, and slowly release chlorantraniliprole, which resulted in significantly higher concentrations of chlorantraniliprole in rice stems and leaves for a prolonged time than suspended and granulated controls. The application of CCAM provided an on-target control of both striped stem borer and pink stem borer. Furthermore, CCAM application had very low residue of chlorantraniliprole in soils. As far as is known, this is the first report of chlorantraniliprole loaded on chitosan-alginate floating hydrogel microspheres for rice stem borer control. Our results indicate that the synthesized CCAM could potentially be used as a controlled-release product for effective control of the two rice pests, while reducing the residual chlorantraniliprole in the soil and avoiding pesticide drift.

Formulation, Characterization and Antihelminthic Activity Testing of Nitazoxanide Superporous Hydrogel Tablets

In the pharmaceutical field controlled release products have the ability to maintain desired medicament concentration or a longer period of time. Certain drugs are relatively insoluble in water and have high dose requirements that render unsuitable formulation difficulties in sustained release formulations. Nitazoxanide which is a high dose water insoluble antiprotozoal drug was formulated with the aim. To modulate gastro-retentive dosage form based on the superporous hydrogel composites. Foaming technique was used in the preparation of SPH composites. The superporous hydrogels were extremely sensitive to pH of swelling media and good porosity. Superporous hydrogels tablets of nitazoxanide showed good pre-compressional and post-compressional properties. Formulation X is the best formulation containing chitosan, polyvinyl alcohol, formaldehyde, exhibited good swelling ratio. The compatibility studies were performed by Fourier Transform Infrared (FT-IR) Spectroscopic Studies, Differential Scanning Calorimetry Studies (DSC). All formulations were evaluated for stability, drug content, and kinetic drug release & in-vitro drug release profile. It was concluded that the proposed gastro-retention drug delivery provides a different supply of nitazoxanide directly to the stomach.
 Keywords: Nitazoxanide, Anti protozoal, foaming technique, Chitosan

Extent and rate of oral drug absorption in minipigs: Comparison with mice, rats and humans

In this study, in order to evaluate the usability of minipigs as an experimental animal in the oral drug development process, extent and rate of oral absorption of 17 commercially drugs were investigated in minipigs and compared with those in mice rats and humans. Extent of oral bioavailability (BA) of tested drugs tended to be lower in minipigs as well as in mice and rats than in humans. From a pharmacokinetic (PK) analysis, it was revealed that the higher activity of intestinal first-pass metabolism, thus the lower intestinal availability, is a major factor causing the lower extent of BA in minipigs, rats and mice than in humans. Whereas the similar value of hepatic availability was observed between minipigs and humans, suggesting the advantage of minipigs to use in oral absorption study for high hepatic clearance drugs. On the other hand, from the plasma concentration-time profiles of orally administered drugs, gastric emptying and intestinal transit rates in minipigs were indicated to be slower than other animals and humans. These slow processes of gastrointestinal transit in minipigs might cause the difficulty in simulating the time-course of plasma concentrations of orally administered drugs in humans, especially as sustained release or controlled release products.

COMPARATIVE IN VITRO DISSOLUTION STUDY ON METFORMIN MARKET PRODUCTS USING DIFFERENT DISSOLUTION APPARATUSES

Objective: This study was proposed to evaluate and compare the in vitro dissolution profiles of six Metformin Hydrochloride (MH) market products.
 Methods: Different dissolution apparatuses (USP apparatus II, IV and beaker method) were used to evaluate the dissolution profiles (in phosphate buffer, pH 6.8) of two immediate release (IR) generic products of Metformin Hydrochloride (MH): Cidophage® 1000 mg (G1, Egyptian market) and Metformin arrow® 1000 mg (G2, French market) with respect to the reference products named Glucophage® 850 mg (R1, Egyptian market and R2, French market). In addition to a generic controlled-release (CR) product; Cidophage Retard® 850 mg (G3) versus the reference product; Glucophage XR® 1000 mg (R3) (both from Egyptian market). Dissolution efficiency (D. E.) and the similarity factor (f2) were calculated. Weight uniformity, hardness, tablet dimensions and MH content were measured.
 Results: Results of the three apparatuses showed that MH IR products studied (reference and generics) did not meet the 75% USP 30 specifications for MH dissolved at 30 min. For MH CR products, Glucophage XR® did not fulfill the USP release criteria, while Cidophage Retard® did. USP apparatus IV revealed the highest sensitivity and discriminative capability.
 Conclusion: Generally, MH IR generics (G1 and G2) might be interchangeable with the innovator product (Glucophage®). However, Cidophage Retard® might not be interchangeable with Glucophage XR®.

Nitrogen and carbon management in Australian mango orchards to improve productivity and reduce greenhouse gas emissions

Australian mango orchards, particularly of the 'Kensington Pride' cultivar, are often characterized by low yields and irregular bearing. Improved nutrition management techniques which increase total soil carbon sequestration and reduce nitrogen losses (nitrous oxide) may improve productivity and also reduce greenhouse gas emissions. A factorial trial was established in a 'Kensington Pride' mango orchard at Mareeba, Australia to assess the benefits of applying organic hay mulch to tree rows in combination with three nitrogen fertiliser treatments including two controlled-release fertiliser products. Three years after the initiation of treatments it was found that mango tree growth and fruit productivity was significantly improved when mulching was used to increase soil organic matter. Mulched soils had improved soil water holding capacity, less temperature variability, increased root biomass in the top soil, greater canopy leaf area and higher plant tissue potassium levels. Average fruit weights were increased by 10% and mango fruit yields per tree increased by 11%. Fruit quality was not affected when standard fungicide management treatments were used, although disease levels were higher with no post-harvest fungicide treatment. The nitrogen fertiliser products investigated did not have a significant influence on mango growth or final productivity. Trial results suggest that the adoption of mulching practices in mango orchards is a management practice which can increase orchard productivity and the sequestration of soil organic carbon, without detrimental effects on fruit quality.

Microsphere: a promising approach for drug delivery

The recent evolution in new drug delivery systems plays a important role in pharmaceutical industries. There are various controlled release products, Microsphere is one among all due to the sustained release and controlled release properties.Microsphere are small spherical shape characteristically free flowing powders, with diameters typically ranging from 1 μm to 1000 μm (1 mm). Microspheres can be produced using several natural and synthetic polymeric materials. Depending on the method, solid or porous microspheres can be obtained for specific intended applications. The variety of methods for the production of microspheres offers numerous opportunities to control the aspects of administration of the API. It provides the prolonged therapeutic action and reduce the dosing frequency, which improve the patient compliance. To get the desired effect the drug should deliver at the target tissue in an ideal amount in the right period of time with maximum therapeutic effect and minimum side effect. Now a day’s microspheres have been used to deliver drugs, vaccines etc. The article is mainly focus on the various aspect of microspheres drug delivery system along with their method of preparation, technique to evaluate its efficiency and pharmaceutical application of microspheres.

Preparation and characterization of Starch–Urea–Borate: A new floating polymer

In recent years considerable attention has been focused on the development of new drug delivery systems known as controlled release drug delivery systems. Such interest is based largely on the fact that the controlled release products have established and retained place in the market based on their uniqueness and their clinical advantages in the practices of medicine. The major types of controlled release systems include matrix tablets, floating tablets, swellable tablets, coated beads, microcapsules and microspheres, mucoadhesive systems, ion exchange resin complexes, osmotic pressure controlled release systems, transdermal systems etc. The principle of floating tablets offers a simple and practical approach to achieve increased gastric residence time to enhance the bioavailability and to obtain controlled release. Floating tablets are designed based on gas generating principle. Design of floating tablets needs a strong matrix forming polymer. Several polymers such as various viscosity grades of hydroxypropylmethyl cellulose (HPMC), Carbopol 934P, Eudragit RL, calcium alginate, chitosan, xanthan gum, guar gum, ethyl cellulose etc., have been used in the design of floating tablets of various active pharmaceutical ingredients (APIs). Though these polymers are available for floating tablets, there is a continued need to develop new, effective and efficient polymers for controlled release floating tablets.The overall objective of the investigation is to develop new, efficient and safe polymer as floating matrix former for floating systems.
 Keywords: Floating, Matrix, Polymers, Starch-urea-borate.

Safe nanotechnologies for increasing the effectiveness of environmentally friendly natural agrochemicals.

Natural compounds and living organisms continue to play a limited role in crop protection, and few of them have reached the market, despite their attractiveness and the efforts made in research. Very often these products have negative characteristics compared to synthetic compounds, e.g., higher costs of production, lower effectiveness, lack of persistence, and inability to reach and penetrate the target plant. Conversely, nanotechnologies are having an enormous impact on all human activities, including agriculture, even if the production of some nanomaterials is not environmentally friendly or could have adverse effects on agriculture and the environment. Thus, certain nanomaterials could facilitate the development of formulated natural pesticides, making them more effective and more environmentally friendly. Nanoformulations can improve efficacy, reduce effective doses, and increase shelf-life and persistence. Such controlled-release products can improve delivery to the target pest. This review considers certain available nanomaterials and nanotechnologies for use in agriculture, discussing their properties and the feasibility of their use in sustainable crop protection, in particular, in improving the effectiveness of natural bio-based agrochemicals. © 2019 Society of Chemical Industry.

APPLICATION AND CHARACTERIZATION OF IN SITU GEL

Applications of in situ gel have been used for a variety of drug delivery routes, such as oral, ocular, rectal, vaginal and injection. Characterization of in situ gel was determined to ensure that the prepared preparation met the standard and it safe. This review describes every aspects of this novel application and characterization of in situ gel preparations, which present the readers an exhaustive detail and might contribute to research and development. In the chemical evaluation in situ gel determined the diffusion of the active substance of a compound by measuring its concentration. In physical evaluation of isotonic calculated by osmotic pressure, drug release was determined by melting point of the substance polymer, gel strength as measured by rheometer, homogenecity test determined by under the light, and stability test with environmental conditions setting. In microbiology evaluation determine if the preparations was contaminated or not, also be effective and safe. Ocular irritation studies-Draize Test us an animal mice or rabbit and determination of visual appearance, clarity, and pH is required. In situ gels offer the primary requirement of a successful controlled release product that is increasing patient compliance.

Physiologically based pharmacokinetic modelling to guide drug delivery in older people.

Older patients are generally not included in Phase 1 clinical trials despite being the population group who use the largest number of prescription medicines. Physiologically based pharmacokinetic (PBPK) modelling provides an understanding of the absorption and disposition of drugs in older patients. In this review, PBPK models used for the prediction of absorption and exposure of drugs after parenteral, oral and transdermal administration are discussed. Comparisons between predicted drug pharmacokinetics (PK) and observed PK are presented to illustrate the accuracy of the predictions by the PBPK models and their potential use in informing clinical trial design and dosage adjustments in older patients. In addition, a case of PBPK modelling of a bioequivalence study on two controlled release products is described, where PBPK predictions reproduced the study showing bioequivalence in healthy volunteers but not in older subjects with achlorhydria, indicating further utility in prospectively identifying challenges in bioequivalence studies.

Application of Chitosan and its Derivatives in Nanocarrier Based Pulmonary Drug Delivery Systems.

The respiratory tract as a non-invasive route of drug administration is gaining increasing attention in the present time on achieving both local and the systemic therapeutic effects. Success in achieving pulmonary delivery, requires overcoming barriers including mucociliary clearance and uptake by macrophages. An effective drug delivery system delivers the therapeutically active moieties at the right time and rate to target sites. A major limitation associated with most of the currently available conventional and controlled release drug delivery devices is that not all the drug candidates are well absorbed uniformly locally or systemically. We searched and reviewed the literature focusing on chitosan and chitosan derivative based nanocarrier systems used in pulmonary drug delivery. We focused on the applications of chitosan in the development of nanoparticles for this purpose. Chitosan, a natural linear bio-polyaminosaccharide is central in the development of novel drug delivery systems (NDDS) including nanoparticles for use in the treatment of various respiratory diseases. It achieves this through its unique properties of biodegradability, biocompatibility, mucoadhesivity and its ability to enhance macromolecule permeation across membranes. It also achieves sustained and targeted effects, primary requirements for an effective pulmonary drug delivery system. This review highlights the applications and importance of chitosan with special emphasis on nanotechnology, employed in the management of respiratory diseases such as asthma, Chronic Obstructive Pulmonary Disease (COPD), lung cancer and pulmonary fibrosis. This review will be of interest to both the biological and formulation scientists as it provides a summary on the utility of chitosan in pulmonary drug delivery systems. At present, there are no patented chitosan based controlled release products available for pulmonary drug delivery and so this area has enormous potential in the field of respiratory science.

Agronomic and physiological aspects of nitrogen use efficiency in conventional and organic cereal-based production systems

AbstractBetter management of synthetic nitrogen (N) fertilizers in conventional agricultural systems laid the foundation for feeding the increasing world's population since the Green Revolution. However, excessive reliance on inorganic fertilizer has resulted in environmental degradation issues. Difficulties in soil nutrition management in organic cropping systems often results in lower and variable yields, also raising questions of sustainability. Improving nitrogen use efficiency (NUE) is thus of key importance to overcome environmental concerns in conventional systems and production limitations in organic systems. The differences in the two farming systems have impacts on crop traits and N cycles, making it difficult to enhance NUE with a single strategy. Different approaches need to be adopted to improve NUE in each system. Extensive efforts have been made to better understand mechanisms to potentially improve NUE in cereal crops under both systems. This review suggests that NUE may be improved through a combination of management practices and breeding strategies specific to the management system. Diversified crop rotations with legumes are effective practices to optimize the N cycle in both conventional and organic systems. Best Management Practices coupled with nitrification inhibitors, controlled release products and split-application practices can reduce N loss in conventional systems. In organic systems, we need to take advantage of available N sources and adapt practices such as no-tillage, cover crops, and catch crops. Utilization of beneficial soil microorganisms is fundamental to optimizing availability of soil N. Estimation of soil organic matter mineralization using prediction models may be useful to enhance NUE if models are calibrated for target environments. Cereal crops are often bred under optimum N conditions and may not perform well under low N conditions. Thus, breeders can integrate genetic and phenotypic information to develop cultivars adapted to specific environments and cultivation practices. The proper choice and integration of strategies can synchronize N demand and supply within a system, resulting in reduced risk of N loss while improving NUE in both conventional and organic systems.

Controlled Release Products for Managing Insect Pests

Controlled Release Products for Managing Insect Pests

842 An open, single dose, anti-tumour effect study of 2-hydroxyflutamide as a controlled release product (Liproca® Depot) injected into the prostate in patients with localized prostate cancer

842 An open, single dose, anti-tumour effect study of 2-hydroxyflutamide as a controlled release product (Liproca® Depot) injected into the prostate in patients with localized prostate cancer

Formulation and development of orodispersible sustained release tablet of domperidone

Commercially available domperidone orodispersible tablets (ODT) are intended for immediate release of the drug, but none of them have been formulated for sustained action. The aim of the present research work was to develop and evaluate orodispersible sustained release tablet (ODT-SR) of domperidone, which has the convenience of ODT and benefits of controlled release product combined in one. The technology comprised of developing sustained release microspheres (MS) of domperidone, followed by direct compression of MS along with suitable excipients to yield ODT-SR which rapidly disperses within 30 seconds and yet the dispersed MS maintain their integrity to have a sustained drug release. The particle size of the MS was optimized to be less than 200 μm to avoid the grittiness in the mouth. The DSC thermograms of MS showed the absence of drug-polymer interaction within the microparticles, while SEM confirmed their spherical shape and porous nature. Angle of repose, compressibility and Hausner’s ratio of the blend for compression showed good flowability and high percent compressibility. The optimized ODT-SR showed disintegration time of 21 seconds and matrix controlled drug release for 9 h. In-vivo pharmacokinetic studies in Wistar rats showed that the ODT-SR had a prolonged MRT of 11.16 h as compared 3.86 h of conventional tablet. The developed technology is easily scalable and holds potential for commercial exploitation.