Co-Precipitation of Acetaminophen and Eugragit Rl 100 Using Supercritical Anti-Solvent in Controlled Drug Delivery

The controlled drug release has been proven to enhance the bioavailability of a drug by maintaining the drug concentration in therapeutic level within certain period of time and lowering the risk of drugs side effects by reducing the frequency of drug administration. Among the available drug administration systems, microcapsule has provided advantages over the conventional mode, due to higher efficiency and flexibility. This microcapsule can be produced by supercritical fluids (SCF) method which currently been used in composite particles production. This application solves the limitations of conventional pharmaceutical methods for the production of active ingredient loaded micro particles. Supercritical anti-solvent (SAS) is one of the SCF methods proven to have good potential in micronization of pure component. In this technique, SCF acts as an anti-solvent for the feed solution and the precipitation occurs when these two media (SCF and feed solution) contact each other. Therefore, the general objective of this study is to widen the application of SAS in the co-precipitation of two components namely acetaminophen in Eudragit RL 100 towards controlling the delivery of the drug. The investigation began with the development of a mathematical model to estimate the rate of mass transfer between a solvent droplet and CO2 during SAS process in the supercritical regime. The simulation results show that, the solvent droplet expands when the solvent is denser than CO2, and shrinks when the CO2 is denser than the solvent. Both of these phenomena occur in less than one second. Based on the developed mathematical model, SAS system with 490ml of precipitation vessel is designed and developed. The design work focuses on the precipitation vessel, particle collector, temperature control system, process stream and selection of spraying device. After the commissioning of the SAS completed, the system is used to determine the optimum operating conditions for co-precipitation of acetaminophen in Eudragit RL 100. The optimum conditions are determined based on the encapsulation efficiency, particle size, product recovery and loading efficiency. The optimum conditions are 110 bars, 35 °C, 1.75 ml/min feed flow rate and 35 mg/ml polymer concentration. The repeatability and consistency of the SAS system is also determined to ensure the accuracy of the results. At least 90% consistency is achieved in the co-precipitation of acetaminophen in Eudragit RL100 as judged by the particles size. In addition, the analysis of fourier transform infra red (FTIR) and thermo gravimetric analyzer (TGA) prove that the association between the acetaminophen and Eudragit RL 100 is physical. The results also show that the SAS process do not change the chemical structure (FTIR and high performance liquid chromatography (HPLC)) and thermal stability (TGA and differential scanning calorimetry (DSC)) of acetaminophen during the process. However, the crystallinity of treated acetaminophen is marginally reduced compared to the untreated acetaminophen (x-ray diffraction (XRD)). More importantly, SAS process has successfully improved the homogenity and size of acetaminophen which is evidenced from the image of scanning electron microscope (SEM). The diffusion coefficient for the release of the processed acetaminophen is also determined by Fick’s second law in this study. In is found that the diffusion coefficient is affected by the particle size and polymer concentration. The estimated diffusion coefficient has a magnitude of 10-14 m2/s. In conclusion, SAS technique has been proven to be one of the promising alternative techniques for co-precipitation of two solutes in drug microcapsules production for controlled drug delivery

Appropriate Drying And Storage Conditions Of Hempedu Bumi (Andrographis Paniculata Nees)

In this study, the forced air thin layer dryer was used for determining the appropriate drying condition of Andrographis paniculata. The quality of dehydrated A.paniculata was evaluated with andrographolide as reference compound. High performance liquid chromatography was used for the determination of andrographolide contained in A.paniculata. A suitable storage condition for preserving andrographolide in ground dried A.paniculata was also determined over a three-month storage study period. Three drying temperatures (55, 65 and 75°C) and air velocities (1.0, 1.5 and 2.0m/s) were utilized for the drying experiment with the observed air relative humidity of 66-80%. Drying temperature was found to be an important parameter affecting the drying time and the quality of A.paniculata. The andrographolide content was reduced by 37.54, 53.59 and 62.72% from the initial amount (17.5 ± 3.4 % wt/dry wt) for the drying temperatures of 55, 65 and 75°C, respectively. However, from the heating cost point of view, 75°C temperature and 1.0m/s air velocity was the appropriate drying condition for A.paniculata. since the cost per unit andrographolide remaining for that drying temperature was the lowest. On the other hand. a larger amount of andrographolide can be maintained with drying condition of 55°C drying temperature and 1.0m/s air velocity. Andrographolide was satisfactorily maintained at three selected storage conditions (5±2°C; 25±2°C with 60±5% RH; 30±2°C with 60±5%RH), which A.paniculata was kept in air tight glass bottle; without any significant reduction of this compound after three months. Therefore, ambient condition (30 ±2°C, 60±5% RH) is acceptable for storage of A.paniculata with respect to andrographolide preservation

Drying behaviour of Andrographis paniculata in vacuum drying

Hempedu bumi (Andrographis paniculata, AP), also known as the king of bitters, is an herb commonly found in Asian communities for medicinal usage. The drying behaviour of AP at temperatures of 40, 50, and 60°C with vacuum pressures of 10 and 30 kPa was investigated in this study. The data were then fitted with semi-theoretical and theoretical thin-layer drying models. The results reveal that the drying time is significantly (p<0.05) affected by temperature and pressure. A two-term, thin-layer model was determined as the most suitable model to fit the drying behaviour of AP. The effective diffusivity and active energy for moisture diffusion were 10-13 m2/s and 33.4 kJ/mol, respectively

Effect of rotation speed and steam pressure on physico-chemical properties of drum dried pitaya (Hylocereus polyrhizus) peel

Red pitaya (Hylocereus polyrhizus) peel is a rich source of fibre, antioxidant and betacyanin; however, it is discarded during processing, so it is able to cause environmental problems. In order to convert the fruit waste to potential by-product ingredients, drum drying is used as pre-treatment to create an ingredient which is shelf-stable. In this study, the effects of rotation speed and steam pressure of drums on the physico-chemical properties of pitaya peel that had undergone drum drying are investigated. Pitaya peel was dried in a laboratory scale double drum dryer at rotation speed of 1, 2, and 3 rpm at steam pressure of 1, 2, and 3 bar. The drum dried pitaya peel was then further analyzed based on percentage yield, moisture content, water activity, betacyanin retention and color change. Interaction of steam pressure and rotation speed gives significant effect (p < 0.05) on percentage yield, moisture content, water activity, betacyanin retention and Hunter L value, whereas it has no significant on Hunter a and b values. The best combination parameters (1 rpm and 2 bar) yield the highest betacyanin retention (80.21 mg/g of dry solid), acceptable moisture content (10.66% wet basis), water activity (aw = 0.42) and with 7.61% of yield

Effects of drying temperature on the chemical and physical properties of Musa acuminata Colla (AAA Group) leaves.

Typically, banana trees are cut once the fruit has been harvested; however, other parts of the banana tree, particularly the leaves, might have other potential uses. Nevertheless, few studies have focused on banana leaves. This work aims to provide information about the effects of different drying temperatures on the antioxidant activity, total phenolic content and physical properties of banana leaves (Musa acuminata Colla (AAA Group)). Leaves were dried at different temperatures (40 °C, 50 °C or 60 °C) using a cabinet dryer with an airflow of 2 m/s. Dried and fresh leaves were analysed for their moisture content, water activity, pH, colour analysis and rehydration index. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Folin–Ciocalteau methods were used to determine the scavenging activity (IC50) and total phenolic content of the fresh and dried leaves extracts, respectively. The results reveal that the drying temperature significantly affects selected properties of banana leaves and 50 °C is proposed as the appropriate drying temperature

Numerical modelling of mass transfer for solvent-carbon dioxide system at supercritical (miscible) conditions

A numerical procedure of mathematical model for mass transfer between a droplet of organic solvent and a compressed antisolvent is presented for conditions such that the two phases are fully miscible. The model is applicable to the supercritical antisolvent (SAS) method of particle formation. In this process, solute particles precipitate from an organic solution when sprayed into a compressed antisolvent continuum. Effects of operating temperature and pressure on droplet behavior were examined. The CO2 critical locus and the conditions for which the densities of solvent and carbon dioxide are equal are identified. Calculations were performed using Peng-Robinson equation of state. The model equations were put into the form that allowed the application of the Matlab standard solver pdepe. Calculations with toluene, ethanol, acetone (solvents) and carbon dioxide (antisolvent) demonstrated that droplets swell upon interdiffusion when the solvent is denser than the antisolvent and shrink when the antisolvent is denser. Diffusion modeling results might be used for data interpretation or experiments planning of the more complex real SAS process

Textural and rheological properties of stevia ice cream

Ice cream contains high sugar content and therefore it is in contradiction with the concept of healthy diet. The objective of this study is to determine the suitability of using stevia as an alternative natural sweetener in making ice cream. In-house ice cream formulation (as the control) and three different concentrations of stevia ice cream formulations of (A, B and C) were used. Physical properties of the ice cream such as the overrun, total soluble solid, meltdown rate, rheology, and textural properties were evaluated. All ice cream samples exhibited a non-Newtonian flow with pseudoplastic behavior. Stevia ice cream has a lower melting rate and has a higher sustainability. The power law also showed that apparent viscosities of stevia ice cream were higher. Therefore, stevia can be used as a natural sugar substitute in ice cream production

Potential effect of Averrhoa bilimbi (belimbing buluh) marinades on tenderizing the buffalo meat compared to Actinidia chinensis (kiwifruit), Citrus limon (lemon) and commercial bromelain

This study was conducted to analyze the effect of Averrhoa bilimbi (belimbing buluh) marinades versus other meat tenderizers on the physicochemical properties of buffalo meat. The buffalo meat chunks were marinated with 40% Averrhoa bilimbi, 40% Citrus limon, 40% Actinidia chinensis, 5% commercial bromelain meat tenderizer (positive control) and distilled water (negative control) for 24 hours at 4°C. The treated samples were cooked at 100°C for 20 minutes. Both raw and cooked samples were subjected to physicochemical analyses. There was significantly lower pH (p<0.05) for raw and cooked meat chunks observed in all treated samples compared to control. Citrus limon and Averrhoa bilimbi showed the lowest pH at 5.04±0.06 and 5.06±0.03, respectively, indicated that the meat chunks were well tenderized. Citrus limon-treated sample recorded the highest (p<0.05) expressible water compared to others. The moisture content of cooked sample and the cooking yield increased significantly (p<0.05) in all treated samples compared to control. The hardness from TPA decreased significantly (p<0.05) for all treated samples compared to control. It can be suggested that Averrhoa bilimbi has the potential to be used as meat tenderizer with the ability to retain the moisture content as compared to other well-known and commercial meat tenderizers

Potential Effect of Averrhoa bilimbi (belimbing buluh) Marinades on Tenderizing the Buffalo Meat Compared to Actinidia chinensis (kiwifruit), Citrus limon (lemon) and Commercial Bromelain

This study was conducted to analyze the effect of Averrhoa bilimbi (belimbing buluh) marinades versus other meat tenderizers on the physicochemical properties of buffalo meat. The buffalo meat chunks were marinated with 40% Averrhoa bilimbi, 40% Citrus limon, 40% Actinidia chinensis, 5% commercial bromelain meat tenderizer (positive control) and distilled water (negative control) for 24 hours at 4°C. The treated samples were cooked at 100°C for 20 minutes. Both raw and cooked samples were subjected to physicochemical analyses. There was significantly lower pH (p&lt;0.05) for raw and cooked meat chunks observed in all treated samples compared to control. Citrus limon and Averrhoa bilimbi showed the lowest pH at 5.04±0.06 and 5.06±0.03, respectively, indicated that the meat chunks were well tenderized. Citrus limon-treated sample recorded the highest (p&lt;0.05) expressible water compared to others. The moisture content of cooked sample and the cooking yield increased significantly (p&lt;0.05) in all treated samples compared to control. The hardness from TPA decreased significantly (p&lt;0.05) for all treated samples compared to control. It can be suggested that Averrhoa bilimbi has the potential to be used as meat tenderizer with the ability to retain the moisture content as compared to other well-known and commercial meat tenderizers

Solubility of red palm oil in supercritical carbon dioxide: measurement and modelling

The solubility of red palm oil (RPO) in supercritical carbon dioxide (scCO2) was determined using a dynamic method at 8.5–25 MPa and, 313.15–333.15 K and at a fixed scCO2 flow rate of 2.9 g·min− 1 using a full factorial design. The solubility was determined under low pressures and temperatures as a preliminary study for RPO particle formation using scCO2. The solubility of RPO was 0.5–11.3 mg·(g CO2)− 1 and was significantly affected by the pressure and temperature. RPO solubility increased with pressure and decreased with temperature. The Adachi–Lu model showed the best-fit for RPO solubility data with an average relative deviation of 14% with a high coefficient of determination, R2 of 0.9667, whereas the Peng–Robinson equation of state thermodynamic model recorded deviations of 17%–30%