Exosomes as a Drug Delivery System in Cancer Therapy: Potential and Challenges.

Exosomes play a pivotal role in mediating intercellular communications and package delivery. They have recently been discovered to serve as diagnostic biomarkers as well as a possible drug delivery vehicle based on their nanometer size range and capability to transfer biological materials to recipient cells. Their unique biocompatibility, high stability, preferred tumor homing, and adjustable targeting efficiency can make exosomes an attractive and potentially effective tool of drug delivery in cancer therapy. While exosomes possess properties that make them uniquely suitable for delivery of bioactive molecules, there remains a to-be-filled gap between the current understanding about exosome biology and the ideal application scenarios. In this review, we summarize the characteristics enabling the potential of exosomes for drug delivery as well as the outstanding questions related to exosome composition and function, production and purification, bioengineering and targeting, uptake and biodistribution, efficacy and immune regulation, etc. Advanced technologies are demanded to visualize, characterize, and sort heterogeneous exosome populations. We are positive that the deeper and more comprehensive understanding of exosome biology as well as advanced nanotechnology will certainly accelerate its therapeutic applications.

Effects of environmental chemicals on fish thyroid function: Implications for fisheries and aquaculture in Australia.

Numerous environmental stressors exert acute or chronic effects on the fish thyroid cascade. Such effects could be mediated via thyroidal alterations, imbalance of plasma T4 and T3 levels or damage to the structure of the thyroidal tissues (thyroid hypertrophy, hyperplasia). The thyroidal system is intricately linked to other endocrine systems in vertebrates including the control of reproduction. Disruption of fish thyroid function by environmental stressors has the potential to result in deleterious effects including the inhibition of sperm production, reduction in egg production, gonad development, ovarian growth, swimming activity, fertilisation and increase in larval mortality. Thyroid hormones play a major role in the development and growth of fish, particularly during their early life stages, thus, thyroid disruption by environmental stressors could inhibit the growth of fish larvae and juveniles in wild fish and cultured species, limit fish seed production and result in a decline in wild fisheries. This review highlights the effects of several environmental toxicants including PBDE, PCBs, PCDD and PCDF, PAH/oil, phthalates, metals, pesticides, mixed pollutants/chemicals, cyanide; and other stressors including acid (low pH) and ammonia, on fish thyroid function. Environmental sources of chemical stressors and appropriate water quality guidelines to protect the freshwater and marine species for the relevant pollutants are also discussed including (when available) the Australian guidelines (2000) and Canadian water quality guidelines (where Australian guidelines are not available). To date there has been no published research on the effects of anthropogenic environmental pollutants on the thyroid system of any native Australian fish species. However, the detection of high risk chemicals (notably PBDEs, PCBs, PAHs, metals and pesticides) in Australian waterways and Australian fish and shellfish implies that thyroid disruption of Australian wild fish and aquacultured species could occur. It is therefore imperative that the effects of such pollutants on the thyroid system of Australian native fish be investigated.

Comparative study of the sensitivities of cancer cells to doxorubicin, and relationships between the effect of the drug-efflux pump P-gp.

Multi-drug resistance (MDR) of cancers to chemotherapy including doxorubicin (DOX) is mediated by several factors. To design an effective therapy for the treatment of chemotherapy-resistant cancers, it is essential to explore the elements responsible for mediating MDR. However, exploring these factors in detail in a wide range of tumor types is challenging as several critical analytical steps are involved. Here, we demonstrated the way of exploring the factors mediating MDR in the tumor types without performing the analysis at the molecular level of cells. The sensitivities of 15 different types of cancer cells to DOX were evaluated, and the role of P-glycoprotein (P-gp), one of the major efflux-pumps, was explored. A correlation curve was developed between the intracellular amounts of DOX and the sensitivities of cells, and, based on this correlation, the cells were classified in response to the involvement of P-gp that mediates MDR. P-gp plays an active role in mediating MDR of cancer cells where a correlation between the sensitivities of cells and the accumulated DOX exists. In contrast, in cells that show a resistance to DOX but whose sensitivities are independent of the amount of accumulated drug, it was reasonably presumed that mechanisms other than P-gp are likely to be involved in mediating MDR. Based on the correlation between the availability of a drug and cell sensitivity, it would be reasonable to explore the factors governing cancer MDR, which is essential in designing an effective therapeutic approach for treating chemotherapy-resistant cancers using chemotherapeutic drugs.

Contamination of coastal and marine bird species with plastics: Global analysis and synthesis.

This review article provides an account of coastal and marine bird species contaminated with plastics in light of ingestion, taxonomy, feeding clusters, types, shapes, colours and lethal and sublethal effects. Bird species were found contaminated with plastics in 39 locations/countries across the seven continents. Global analysis shows that low, medium and high plastic ingestion occurred in bird species across the globe. Fulmars, shearwaters, petrels, albatrosses, gulls, and kittiwakes (all marine/seabirds) were found contaminated with plastics in several locations in the world. Bird species belonging to the Procellariidae, Laridae, Diomedeidae (by taxonomy), piscivorous, molluscivorous, and cancrivorous (by feeding habits) were most contaminated with plastics. Microplastic, mesoplastic and macroplastic (by sizes), PP, PE, PS, PET, PAN and PVC (by types), fragments, pellets, fibres, foams, sheets, threads, fishing lines and films (by shapes) and white, blue, green, black, clear, red and yellow (by colours) were the most common plastics ingested by birds. Several bird species contaminated with plastics fall within the critically endangered, endangered and vulnerable categories. The ingestion of plastics can cause direct harm to birds resulting in death. In addition, plastic-derived toxic chemical additives and plastic-adsorbed toxic chemicals would be an additional stressor causing both lethal and sublethal effects that can cause greater harm to the health of birds. Several measures are suggested to reduce plastic pollution in the environment to safeguard birds and the environment.

"Microplastic seasoning": A study on microplastic contamination of sea salts in Bangladesh.

This study investigated microplastics (MPs) in commercial sea salts from Bangladesh. The presence of MPs in the 18 sea salt bands was 100 %, where the mean MPs abundance was 471.67 MPs/kg, ranging between 300 and 670 MPs/kg. The maximum number of MPs in the 300-1500 µm size class was significantly higher than the 1500-3000 µm and 3000-5000 µm size class. The most dominant color was black. Fibers and foams were the dominant shapes. The highest number of MPs was 41 %, obtained from coarse salt grains. Four types of polymers were mainly identified from the analyzed samples: PP, PE, PET, and PA. The mean polymer risk index value among these sea salts was 539 to 1257. The findings of this study can be helpful for consumers, salt industries, and policymakers to be aware of or reduce MP contamination levels in sea salts during production and consumption.

Calibration and field application of Chemcatcher® passive samplers for detecting amitrole residues in agricultural drain waters.

A passive sampler device suitable for monitoring of residues of the hydrophilic ionic herbicide amitrole in irrigation waterways was developed. Uptake of amitrole on styrenedivinylbenzene-reverse phase sulfonated Empore™ disks was linear and proportional to its water concentration over the range of 1-10 µg/L with a sampling rate of 23.1 mL/day under laboratory flow-through conditions. Performance of the sampler was evaluated by deployment in an agricultural irrigation drain for 10 days. The amount of amitrole adsorbed by the passive samplers compared well with the cumulative mean water concentrations calculated from daily spot samplings of the drain water.

Impacts of microplastic on fisheries and seafood security - Global analysis and synthesis.

This review paper collected, collated, analysed, interpreted, synthesised, and documented the research investigations conducted on microplastic (MPs) pollution impacts on seafood organisms (including fish, sharks, shrimps, lobsters, crabs, oysters, mussels, and seaweeds) during the last ten years (2012-2022) covering fifty-seven locations/countries in the world. MPs contaminated 926 seafood species comprising 895 finfish, 09 crustaceans, 20 molluscs and 02 seaweeds. Seafood from Asia was found to be most contaminated with MPs. High MP contamination/ingestion was revealed in several seafood organisms. The ingestion of MPs can reduce fish growth and fish fitness, leading to reduced yield/fish production. Fish and seafood play a significant role in supporting the economy, employment, food sources, and livelihoods of people across the globe, which can be threatened due to the contamination of seafood organisms with MPs. MPs have bioaccumulated in fish skin, gills, stomachs, liver, intestine, and muscles as well as dry fish and canned fish. Hence, the consumption of MP-contaminated fresh fish, whole fish, dried fish or canned fish poses risks as it may be a pathway of MP transfer to humans. MPs can increase the health risks to seafood fish consumers since there is a probability that high risks pollutants adsorbed on MPs (heavy metals, pesticides, and oil compounds) can transfer to humans via the food chain. Several of the chemicals (heavy metals, DDT, PAHs) adsorbed onto MPs are carcinogenic. MPs have also been detected in fish meals, therefore, farmed livestock such as aquaculture fish and chicken fed to fish meals can be exposed to MPs and ultimately to humans. Preventive and safety measures are suggested to reduce the exposure of MPs to humans. In addition, several policy strategies are recommended to reduce the impacts of plastic waste and plastic pollution on the environment, aquatic biota, wildlife, seafood and human health.

Stability of Abuse-deterrent properties of PEO-based Abuse-deterrent formulation.

Abuse of opioid drug products is a national health crisis in the US. To deter abuse, a number of drug products with abuse-deterrent (AD) properties have been approved by the US Food and Drug Administration (FDA). For abuse deterrence, it is critical to maintain the AD properties during the product shelf life. However, no information on the stability of AD properties during product shelf life is publicly available. In this study, stability of AD properties of surrogate AD formulation (ADF) of opioid active pharmaceutical ingredients (APIs) were studied. Surrogate extended release (ER) AD tablets were prepared by direct compression using Diltiazem HCl (model drug), polyethylene oxide (PEO WSR 301) polymer and magnesium stearate followed by curing at 70 °C for 30 mins. The stability studies were conducted at 25 °C/60 % RH and 40 °C/75 % RH storage conditions for 12 months (M) and 6 months (M), respectively. In vitro characterization and evaluation of AD properties of tablets were performed. As anticipated, the curing process increased the crushing strength of the tablets. However, the tablets could still be manipulated and compromised leading to an enhancement in the amount of drug extracted in solvents (e.g., water, alcohol), regardless of extraction temperature as well as tablet storage condition and time. Furthermore, the granule particle size as well as viscosity in water of manipulated samples were found to be lower for tablets stored at 25 °C/60 % RH or 40 °C/75 % RH for 12 M or 3 M/6M, respectively. The changes in AD properties eased the syringeability of hydrated samples and ultimately led to the withdrawal of higher amounts of drug into the syringe, thereby, impacting the abuse deterrence potential of the formulation by an IV route. These data demonstrated that the stability of AD properties (i.e., granule particle size, viscosity and syringeability-injectability) of PEO-based tablets was dependent on the storage condition. In conclusion, the design of AD formulation and setting of product quality profile should take into consideration the stability of AD properties during the product shelf life.

Heavy metals and metalloids in edible seaweeds of Saint Martin's Island, Bay of Bengal, and their potential health risks.

The present study aimed to assess the levels of heavy metals and metalloids present in six seaweeds and their potential impact on consumption. The highest concentration of 11 metals, i.e., Be (0.47 mg/kg), Co (4.34 mg/kg), Cr (23.46 mg/kg), Cu (11.96 mg/kg), Fe (2290.26 mg/kg), Li (11.55 mg/kg), Ni (13.75 mg/kg), Pb (6.67 mg/kg), Ti (736.62 mg/kg), Tl (0.14 mg/kg), and V (33.09 mg/kg) were observed in Enteromorpha intestinalis (green seaweeds). Besides, the highest concentration of Ca (1071.09 mg/kg), Cd (5.81 mg/kg), Mn (1003.41 mg/kg), Sr (2838.86 mg/kg), and Zn (41.95 mg/kg) were found in Padina tetrastromatica (brown seaweeds). Eight metals (Pb, Cd, Zn, Cu, Ni, Mn, Cr, Fe) have been used to assess the potential health risk for adults, but no potential health risk was detected (HQ value > 1). The HI value of E. intestinalis and P. tetrastromatica were >1, implying that these two seaweeds are not safe for human consumption as there is a carcinogenic health risk for adults.

Microplastics in an anadromous national fish, Hilsa shad Tenualosa ilisha from the Bay of Bengal, Bangladesh.

Hilsa shad is one of the most important fisheries, contributing about 12.9% of the country's (Bangladesh) total fish production. There was no previous study on microplastic contamination of this important commercial fish. This study aims to identify, classify, and quantify microplastics (MPs) ingested by the national fish of Bangladesh, Hilsa shad, Tenualosa ilisha. A total of 287 MPs were recovered from the gastrointestinal tracts. All the fishes analyzed were contaminated with MPs. The mean (±SD) of the number of MPs was 19.13 ± 10.77 particles/fish, ranging from 7 to 51 particles/fish. Significant correlation was not found between the fish body length and MP abundance (rs = 0.287, p = 0.299), and between the fish body weight and MPs abundance (rs = 0.261, p = 0.347). The most dominant color was transparent (30%), followed by gray and black, contributing to 26% and 23%, respectively. The maximum number of MPs accounted for in the 300-1500 µm size class where fiber was the most dominant (50%) shape of observed MPs. These results provide a baseline of MP contamination in seafood from Bangladesh that should be useful for future monitoring efforts. The present study is the first research on MP contamination of Hilsa shad.

Plasma VP8∗-Binding Antibodies in Rotavirus Infection and Oral Vaccination in Young Bangladeshi Children.

BACKGROUND: Despite the availability and success of live-attenuated oral vaccines, rotavirus (RV) remains the leading cause of pediatric gastroenteritis worldwide. Next-generation vaccines targeting RV VP8∗ are under evaluation, but the role of VP8∗-specific antibodies in human immunity to RV and their potential as immune correlates of protection remains underexplored. METHODS: We measured plasma RV VP8∗-binding antibodies in 2 cohorts of young children in Dhaka, Bangladesh. Plasma from a cohort study of 137 unvaccinated children aged 6-24 months old hospitalized with acute gastroenteritis was assessed for VP8∗ antibody seropositivity. VP8∗ antibodies were compared with the current standard for RV immunity, total RV-specific IgA (RV-IgA). Additionally, VP8∗ antibody responses were measured as part of an immunogenicity trial of a monovalent, oral, live-attenuated RV vaccine (Rotarix). RESULTS: Fewer children with acute RV gastroenteritis were seropositive for VP8∗-binding IgA or IgG antibodies at hospital admission compared with RV-IgA, suggesting that the absence of VP8∗-binding antibodies more accurately predicts susceptibility to RV gastroenteritis than RV-IgA in unvaccinated children. However, when present, these antibodies appeared insufficient to protect fully from disease and no threshold antibody level for protection was apparent. In vaccinated children, these antibodies were very poorly induced by Rotarix vaccine, suggesting that VP8∗-specific antibodies alone are not necessary for clinical protection following oral vaccination. CONCLUSIONS: This work suggests that VP8∗-binding antibodies may not be sufficient or necessary for protection from RV gastroenteritis following prior RV infection or oral vaccination; the role of VP8∗ antibodies induced by parenteral vaccination with non-replicating vaccines remains to be determined.

Climate change impacts on pollutants mobilization and interactive effects of climate change and pollutants on toxicity and bioaccumulation of pollutants in estuarine and marine biota and linkage to seafood security.

This article provides an overview of the impacts of climate change stressors (temperature, ocean acidification, sea-level rise, and hypoxia) on estuarine and marine biota (algae, crustaceans, molluscs, corals, and fish). It also assessed possible/likely interactive impacts (combined impacts of climate change stressors and pollutants) on pollutants mobilization, pollutants toxicity (effects on growth, reproduction, mortality) and pollutants bioaccumulation in estuarine and marine biota. An increase in temperature and extreme events may enhance the release, degradation, transportation, and mobilization of both hydrophobic and hydrophilic pollutants in the estuarine and marine environments. Based on the available pollutants' toxicity trend data and information it reveals that the toxicity of several high-risk pollutants may increase with increasing levels of climate change stressors. It is likely that the interactive effects of climate change and pollutants may enhance the bioaccumulation of pollutants in seafood organisms. There is a paucity of literature relating to realistic interactive effects of climate change and pollutants. Therefore, future research should be directed towards the combined effects of climate change stressors and pollutants on estuarine and marine bota. A sustainable solution for pollution control caused by both greenhouse gas emissions (that cause climate change) and chemical pollutants would be required to safeguard the estuarine and marine biota.

Unbiased K-L estimator for the linear regression model.

Background: In the linear regression model, the ordinary least square (OLS) estimator performance drops when multicollinearity is present. According to the Gauss-Markov theorem, the estimator remains unbiased when there is multicollinearity, but the variance of its regression estimates become inflated. Estimators such as the ridge regression estimator and the K-L estimators were adopted as substitutes to the OLS estimator to overcome the problem of multicollinearity in the linear regression model. However, the estimators are biased, though they possess a smaller mean squared error when compared to the OLS estimator. Methods: In this study, we developed a new unbiased estimator using the K-L estimator and compared its performance with some existing estimators theoretically, simulation wise and by adopting real-life data. Results: Theoretically, the estimator even though unbiased also possesses a minimum variance when compared with other estimators.  Results from simulation and real-life study showed that the new estimator produced smaller mean square error (MSE) and had the smallest mean square prediction error (MSPE). This further strengthened the findings of the theoretical comparison using both the MSE and the MSPE as criterion. Conclusions: By simulation and using a real-life application that focuses on modelling, the high heating values of proximate analysis was conducted to support the theoretical findings. This new method of estimation is recommended for parameter estimation with and without multicollinearity in a linear regression model.

Spatial and temporal variations of trace metal body burdens of live mussels Mytilus galloprovincialis and field validation of the Artificial Mussels in Australian inshore marine environment.

The body burdens of eight trace metals: Cd, Pb, Cu, Zn, Cr, Se, Hg, and As, were measured in live mussels (LMs) Mytilus galloprovincialis at 14 coastal sites in Port Phillip Bay, Victoria, Australia in winter and summer between 2017 and 2018. The spatial and temporal variations of body burdens were evaluated. The results revealed significantly higher body burdens of Cd, Pb, Cu, Zn, Cr, and Hg in summer at the sites where the city centre and industries are located. Elevated levels of most trace metals including 3 toxic, non-essential metals (Cd, Pb, and Hg) were detected in LMs from the site of Geelong. The body burdens of Zn, Cr, Se, and As appeared higher at the sites from the Bellarine Peninsula and the mouth of Port Phillip Bay. Besides, the "Artificial Mussels" (AMs) were deployed at the same sites in summer for 28 d and retrieved when the LMs were collected. The accumulations of the eight metals were compared between AMs and LMs summer results. It indicated significant correlations for Pb, Cu, and Cr, lower correlations in Zn and Hg, and irregular correlations for Se and As. The AM results of Cd were below the detection limit of the analytical method. This study demonstrates that AMs are excellent replacement of LMs for the biomonitoring of multiple kinds of trace metals.

Predictive modelling of COVID-19 confirmed cases in Nigeria.

The coronavirus outbreak is the most notable world crisis since the Second World War. The pandemic that originated from Wuhan, China in late 2019 has affected all the nations of the world and triggered a global economic crisis whose impact will be felt for years to come. This necessitates the need to monitor and predict COVID-19 prevalence for adequate control. The linear regression models are prominent tools in predicting the impact of certain factors on COVID-19 outbreak and taking the necessary measures to respond to this crisis. The data was extracted from the NCDC website and spanned from March 31, 2020 to May 29, 2020. In this study, we adopted the ordinary least squares estimator to measure the impact of travelling history and contacts on the spread of COVID-19 in Nigeria and made a prediction. The model was conducted before and after travel restriction was enforced by the Federal government of Nigeria. The fitted model fitted well to the dataset and was free of any violation based on the diagnostic checks conducted. The results show that the government made a right decision in enforcing travelling restriction because we observed that travelling history and contacts made increases the chances of people being infected with COVID-19 by 85% and 88% respectively. This prediction of COVID-19 shows that the government should ensure that most travelling agency should have better precautions and preparations in place before re-opening.

Stability study of ambroxol hydrochloride sustained release pellets coated with acrylic polymer.

The aim of the present study is to perform stability study of ambroxol hydrochloride sustained release pellets stored in different storage conditions. The drug loaded beads were prepared by extrusion-spheronization technology then coated with ammonio methacrylate copolymer type A (Eudragit RL 30 D) and ammonio methacrylate copolymer type B (Eudragit RS 30 D) at a ratio of 2:3 (8% polymer by weight on dry basis) in fluid bed coater (Wurster column). Stability study of pellets was performed as capsule dosage form in aluminium-PVDC packaging mode at room temperature, 40 degrees C, 40 degrees C/75%RH & 30 degrees C/70%RH for three months. After one month the shape & size of the pellets was changed in all conditions. The color of the pellets remains unchanged up to the 2nd month in all conditions except at 40 degrees C/75%RH and in this case some pellets become brown. But after 3rd month, pellets become brownish in all conditions except at room temperature. At RT the color of pellets remains unchanged during the stability study. The mean drug content decreased gradually in all conditions. In acid media the initial drug release was 23% but after 1st month it was decreased to 13-15% in all conditions. In the buffer media (pH 6.8) the drug release was increased a little bit in all conditions except at 30 degrees C/70%RH with the passes of storage time. Stability studies at 30 degrees C/70%RH revealed consistent drug release (f(2)>50) throughout the stability period. The physical properties of pellets as well as the in vitro release profile of the drug was found to be a function of the different storage conditions as well as the physico-chemical nature of the polymers.

Antibiotic Use: A Cross-Sectional Study Evaluating the Understanding, Usage and Perspectives of Medical Students and Pathfinders of a Public Defence University in Malaysia.

Background: Antimicrobial prescribing behaviors are often influenced by the local culture and prescribing appropriateness of medical doctors and other health care professionals. Globally, antimicrobial utilization practices have a profound impact on antimicrobial resistance and are a tremendous public health concern. The aim of this survey was to explore the knowledge and attitudes of medical students from the National Defence University of Malaysia regarding antimicrobial usage and antimicrobial resistance. Research design and methods: This was a cross-sectional study. The study population consisted of undergraduate medical students in each year group from the National Defence University of Malaysia. Students receive limited formal training on the use of antibiotics in their curriculum, and most of this learning is opportunistic whilst on clinical placement. Universal sampling was used as the study population was small. Data were collected utilizing a previously validated instrument regarding antibiotic use. Simple descriptive statistics were used to generate frequencies and percentages with SPSS V21. This research was approved by the Centre for Research and Innovation Management, National Defence University of Malaysia. Results: 206 questionnaires were distributed with a response rate of 99.03%, 54% (110) male, and 46% (94) female. Out of the respondents, 65% (132) had used antibiotics in the last year. Respondents displayed a moderate level of knowledge about antibiotics. Conclusions: This study revealed that the older the student was, or when the year of study and total knowledge score was higher, the students were less likely to stop antimicrobials when they felt better or use leftover antibiotics without consulting a doctor. Therefore, the nearer the students were to graduation, the better their knowledge and skills were, and this translated into their own behaviors regarding use of antimicrobials. This finding has clear implications for curriculum design and the inclusion of formal teaching throughout the medical program on antimicrobial use and antimicrobial resistance (AMR). However, more research is needed on this topic, including the prescribing habits and antibiotic use of practicing doctors.

Self-medication of antibiotics: investigating practice among university students at the Malaysian National Defence University.

Background: Self-medication of drugs to alleviate symptoms is a common global behavior, helping relieve burdens on health services, but many drugs eg, antibiotics are prescription-only. Self-medication of antibiotics (SMA) is an irrational use of drugs, contributing to microbial resistance increasing health care costs and higher mortality and morbidity. This study aimed to assess SMA among university students. Methods: This was a cross-sectional study conducted among medical and non-medical students of the National Defence University of Malaysia. A validated instrument was used to gather data. Ethics approval was obtained. Random and universal sampling was adopted, and SPSS 21 was used for data analysis. Results: A total of 649 students participated in the study: 48.5% male and 51.5% female, 39.3% reported self-medicating with antibiotics. Penicillin, doxycycline, clarithromycin were the antibiotics most used with the majority reporting no adverse drug reactions. Cost savings and convenience were the principal reasons for SMA which were mainly obtained from local retail pharmacies. Despite medical students (particularly the more senior) having better knowledge of antibiotic use than non-medical students, 89% of all research participants responded that practicing SMA was a good/acceptable practice. Conclusion: SMA is common amongst Malaysian students and, despite understanding why SMA is unwise, even medical students self-medicate.

Effect of plasticizer on release kinetics of diclofenac sodium pellets coated with Eudragit RS 30 D.

The present study was designed to investigate the effect of two plasticizers, i.e., triethyl citrate (TEC) and polyethylene glycol 6000 (PEG 6000) on the in vitro release kinetics of diclofenac sodium from sustained-release pellets. Ammonio methacrylate copolymer type B (Eudragit RS 30 D) is used as the release-retarding polymer. Both plasticizers were used at 10% and 15% (w/w) of Eudragit RS 30 D. Pellets were prepared by powder layering technology and coated with Eudragit RS 30 D by air suspension technique. Thermal properties of drug and drug-loaded beads were studied using differential scanning calorimeter (DSC). DSC thermogram represented the identity of raw materials and exhibited no interaction or complexation between the active and excipients used in the pelletization process. Dissolution study was performed by using USP apparatus 1. No significant difference was observed among the physical properties of the coated pellets of different batches. When dissolution was performed as pure drug, about 8.22% and 90% drug was dissolved at 2 h in 0.1 N HCl and at 30 min in buffer (pH 6.8), respectively. From all formulations, the release of drug in acid media was very negligible (maximum 1.8 +/- 0.08% at 2 h) but in buffer only 12% and 30% drug was released at 10 h from coated pellets containing TEC and PEG 6000, respectively, indicating that Eudragit RS 30 D significantly retards the drug release rate and that drug release was varied according to the type and amount of plasticizers used. The amount of TEC in coating formulation significantly effected drug release (p < 0.001), but the effect of PEG 6000 was not significant. Formulations containing PEG 6000 released more drug (98.35 +/- 2.35%) than TEC (68.01 +/- 1.04%) after 24 h. Different kinetic models like zero order, first order, and Higuchi were used for fitting drug release pattern. Zero order model fitted best for diclofenac release in all formulations. Drug release mechanism was derived with Korsmeyer equation.

The effect of the ratio of two acrylic polymers on the in vitro release kinetics of ketoprofen from pellets prepared by extrusion and spheronisation technique.

The aim of this study was to investigate the effect of physico-chemical properties of the polymers on the release profile of ketoprofen from the pellets dosage form. Ammonio Methacrylate Copolymer Type A (Eudragit RL 30 D) & Ammonio Methacrylate Copolymer Type B (Eudragit RS 30 D) were used as release rate retarding polymers. The drug containing core pellets were prepared by extrusion spheronisation technique and subsequently coated with 15% (w/w) polymer load of the combination of Eudragit RL 30 D & Eudragit RS 30 D having ratio 1:0, 4:1, 3:2, 1:1, 2:3, 1:4, 0:1 respectively. Significant differences were found among the drug release profile from different formulations. It was revealed that Eudragit RL 30 D has the effect to increase the initial drug release more significantly where as Eudragit RS 30 D has the effect to minimize the initial drug release but increase the terminal drug release more significantly. In acid media about 50% drug was released from pellets coated only with Eudragit RL 30 D where as only 5% drug was released in case of Eudragit RS 30 D but maximum 10% drug was released from pellets when coated with the combination of Eudragit RL 30 D & Eudragit RS 30 D. In buffer media, evidence of burst release was observed for the pellets coated with Eudragit RL 30 D & Eudragit RS 30 D having ratio of 1:0, 4:1, 3:2 respectively. It was also observed that drug release increases sharply as well as the release best fit to the zero order release kinetics when pellets coated with 1:1 ratio of Eudragit RL 30 D & Eudragit RS and follows Higuchi's release kinetics when ratio was 1:0 & 3:2. The results generated in this study showed that proper selection of polymeric materials based on their physico-chemical properties is important in designing sustained release pellets dosage form with suitable dissolution profile.