Scaling of continuous twin screw wet granulation

Scaling rules were developed and tested for a continuous twin screw wet granulation process using three scales (11, 16, and 24 mm barrel diameter) of twin screw granulators (TSG). The distributive feed screw configuration used produced high porosity granules (50-60%) with broad bimodal size distributions, especially in the 16 and 24 mm TSGs. Three dimensionless numbers, Froude number (Fr), liquid-to-solid ratio (LSR), and powder feed number (PFN), were identified and their effect on granule size distribution (GSD), porosity and liquid distribution tested. Granule size increased with increasing LSR as expected. However, Fr and PFN had no significant effect on d10 or d50 and only a small effect on d90. In contrast, granulator scale had a strong effect on GSD, with d90 increasing almost linearly with barrel diameter. This is consistent with breakage of large granules being a dominant mechanism and directly controlled by the geometry of the screw

ANTIDIABETIC, HYPOLIPIDEMIC AND ANTIOXIDANT ACTIVITIES AND PROTECTIVE EFFECTS OF PUNICA GRANATUM PEELS POWDER AGAINST PANCREATIC AND HEPATIC TISSUES INJURIES IN STREPTOZOTOCIN INDUCED IDDM IN RATS

Objective: There is a growing interest in traditional medicinal plants since they contain medicinally active products to remedy many diseases. Punica granatum (PG) has many medicinal applications. The aim of this study was to investigate the antidiabetic, hypolipidemic, antioxidant and hepato-pancreatic protective effects of PG peel powder (PGPP) on streptozotocin (STZ) induced diabetic rats.Methods: Male Swiss albino rats became diabetic with insulin-dependent diabetes mellitus (IDDM) after a single intravenous injection of STZ (50 mg/kg). IDDM-rats received either a daily oral dose of PGPP (200 mg/kg), or insulin for 20 days. On day 21, rats were sacrificed and levels of fasting blood glucose (FBG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, lipid profile, lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD), and total antioxidant capacity (TAC) were estimated. Histopathological studies of liver and pancreas were performed.Results: There was a significant elevation in FBG, AST, ALT activities, NO and LPO levels for induced IDDM. In contrast, albumin level, SOD activity, and TAC exhibited the significant decline. In addition, there was marked lipid profile disturbances, and histopathological changes of liver and pancreas. Following PGPP supplementation, the levels of all the above-mentioned factors were back to normal. Also, liver architecture and the size of an islets of Langerhans of the pancreas were almost back to normal. The effect of PGPP was more pronounced when compared with insulin.Conclusion: PGPP is an effective alternative for the treatment of IDDM through the regeneration of β cells of pancreas and via its strong antioxidant properties.Â

Representing spray zone with cross flow as a well-mixed compartment in a high shear granulator

The spray zone is an important region to control nucleation of granules in a high shear granulator. In this study, a spray zone with cross flow is quantified as a well-mixed compartment in a high shear granulator. Granulation kinetics is quantitatively derived at both particle-scale and spray zone-scale. Two spatial decay rates, DGSDR (droplet-granule spatial decay rate) ζDG and DPSDR (droplet-primary particle spatial decay rate) ζDP, which are functions of volume fraction and diameter of particulate species within the powder bed, are defined to simplify the deduction. It is concluded that in cross flow, explicit analytical results show that the droplet concentration is subject to exponential decay with depth which produces a numerically infinite depth of spray zone in a real penetration process. In a well-mixed spray zone, the depth of the spray zone is 4/(ζDG + ζDP) and π2/3(ζDG + ζDP) in cuboid and cylinder shape, respectively. The first-order droplet-based collision rates of, nucleation rate B0 and rewetting rate RW0 are uncorrelated with the flow pattern and shape of the spray zone. The second-order droplet-based collision rate, nucleated granule-granule collision rate RGG, is correlated with the mixing pattern. Finally, a real formulation case of a high shear granulation process is used to estimate the size of the spray zone. The results show that the spray zone is a thin layer at the powder bed surface. We present, for the first time, the spray zone as a well-mixed compartment. The granulation kinetics of a well-mixed spray zone could be integrated into a Population Balance Model (PBM), particularly to aid development of a distributed model for product quality prediction

A novel methodology to study polymodal particle size distributions produced during continuous wet granulation

It is important during powder granulation to obtain particles of a homogeneous size especially in critical situations such as pharmaceutical manufacture. To date, homogeneity of particle size distribution has been defined by the use of the d50 combined with the span of the particle size distribution, which has been found ineffective for polymodal particle size distributions. This work focuses on demonstrating the limitations of the span parameter to quantify homogeneity and proposes a novel improved metric based on the transformation of a typical particle size distribution curve into a homogeneity factor which can vary from 0 to 100%. The potential of this method as a characterisation tool has been demonstrated through its application to the production of granules using two different materials. The workspace of an 11 mm twin screw granulator was defined for two common excipients (?-lactose monohydrate and microcrystalline cellulose). Homogeneity of the obtained granules varied dramatically from 0 to 95 % in the same workspace, allowing identification of critical process parameters (e.g. feed rate, liquid/solid ratio, torque velocities). In addition it defined the operational conditions required to produce the most homogeneous product within the range 5 ?m – 2.2 mm from both materials

A review of current techniques for the evaluation of powder mixing

Blending a mixture of powders to a homogeneous system is a crucial step in many manufacturing processes. To achieve a high quality of the end product, powder mixtures should be made with high content uniformity. For instance, producing uniform tablets depends on the homogeneous dispersion of active pharmaceutical ingredient (API), often in low level quantities, into excipients. To control the uniformity of a powder mixture, the first required step is to estimate the powder content information during blending. There are several powder homogeneity evaluation techniques which differ in accuracy, fundamental basis, cost and operating conditions. In this article, emerging techniques for the analysis of powder content and powder blend uniformity, are explained and compared. The advantages and drawbacks of all the techniques are reviewed to help the readers to select the appropriate equipment for the powder mixing evaluation. In addition, the paper highlights the recent innovative on-line measurement techniques used for the non-invasive evaluation of the mixing performance

Development of Near-IR Spectroscopic and Imaging Methods for Process Control of Pharmaceutical Powder Blending

The Process Analytical Technology (PAT) initiative, undertaken by the Food and Drug Administration (FDA), paves the way for improvement of drug manufacturing through real-time measurements that allow better process understanding. In this work, Near-Infrared spectroscopy (NIRS) was used to monitor powder blending through optical ports mounted on the blender. Preliminary studies demonstrated that active ingredient concentration and processing conditions affected the mixing end point. The advantages and limitations of different chemometric algorithms in blend uniformity analysis were evaluated, with an ultimate goal of developing a global model that could be used for prediction of future samples. The limitation of Curve-Fitting to Mean Standard Deviation-Time Data technique as a sole measure of homogeneity was apparent because it measures spectral variability without being sensitive to potency changes. In contrast, pattern recognition approaches, such as Soft Independent Modeling of Class Analogies (SIMCA), were more reliable owing to their sensitivity to %potency and variability changes. The NIR-analyzed sample mass was estimated to be between 5.5 and 6.4 mg, highlighting the importance of monitoring blends from multiple locations to ensure representative sampling. An experimental design approach was used to characterize the effect of humidity, component concentration, and blender speed on mixing end point. All three variables were shown to significantly impact the blending process. Furthermore, humidity and concentration had a significant effect on particle size and density of powder mixtures. Qualitative algorithms such as SIMCA and Bootstrap Error-adjusted Single-sample Techniques (BEST) were evaluated. Optimization of NIR models was achieved by spectral processing, and training set sample selection. The models developed were successful in predicting blend homogeneity of independent blend samples. A quantitative NIR model for blending end point prediction was also developed. Process signature was built into NIR models by using spectra of actual blend experiments. Evaluation of principal component regression (PCR), partial least squares (PLS) and multi-term linear regression (MLR) showed that a single wavelength-linear regression yielded optimum results. The blending profiles predicted by the NIR quantitative model correlated well to those determined by the UV method. Characterization of intra-shell versus inter-shell powder mixing kinetics and its implication in sensor positioning was also performed

Application of halo polyhydroxy polyurethane foam for the extraction of cobalt from cobalamin drugs and urine

<p>Polyhydroxy polyurethane sorbent was modified by the addition of halogen atoms to its matrix to produce a new sorbent distinguished by high surface polarity, enhanced capacity, and improved stability in both acidic and alkaline media. Halo polyhydroxy polyurethane foam (X-PPF) was characterized by NMR, FTIR, UV–Vis, Raman spectroscopy, pH_ZCP values, and scanning electron microscopy images. Experimental studies have proven that X-PPFs have a great potential for the extraction and recovery of cobalt ions and this was attributed to the presence of halogen, phenolic, and urethane groups. The pH_ZCP value of X-PPFs was determined to be 0.91 and the maximum metal recovery was achieved at a pH range of 6–7. The kinetics of the process was best described by pseudo-second-order model (<i>R</i>² = 1). Δ<i>H</i>, Δ<i>S</i>, and Δ<i>G</i> values were calculated to be −57.2 kJ mol⁻¹, −172.6 J K⁻¹ mol⁻¹, and −5.8 kJ mol⁻¹, respectively. A perfect isotherm curve with zero intercept (0.002), good correlation (<i>R</i>² = 0.999), and capacity of 246.8 mg g⁻¹ was obtained.</p