Avicel PH Research Articles

The Microstructure and Potential of Chondroitin Sulfate in Shark Cartilage Extract

Shark (Prionace glauca) cartilage is an industrial waste of the frozen fish industry in Sidoarjo city. Previous studies indicate that the cartilage contains bioactive compounds, glucosamine, and chondroitin, but the extracted product is unstable (easily melted during storage) and smelly ammonia. This study aims to obtain a stable extract product without the smell of ammonia by adding different absorbers. The experiment used a Complete Randomized Design on applying absorbers, HPMC, Cab-Osil, and Avicel PH 101. The parameters measured were the yield and the organoleptic of the shark’s extract product. The microstructural observations used a Scanning Electron Microscope (SEM), while the chondroitin sulfate content analyses used high-performance liquid chromatography(HPLC). Results showed that adding different absorbers significantly influenced the yield and organoleptic of the shark’s cartilage extract. The use of Avicel PH 101 (90%), Cab-Osil (9%), and Hydroxy Propyl Methyl Cellulose (HPMC) (1%) gave the highest amount of extract, as much as 5.02 g (16.73%). The organoleptic was without smelling salts, whitish beige color, and dry structure (stable). The microstructure of the shark’s cartilage extract product at this treatment had a dense structure with a soft surface. In contrast, the extract without an absorber addition had a sharp, needle-like microstructure. The chondroitin sulfate content of the shark’s cartilage extract product was the highest at this treatment.

Quality-by-Design-Based Development of Rivaroxaban-Loaded Liquisolid Compact Tablets with Improved Biopharmaceutical Attributes.

Rivaroxaban (RXN) finds use in the management of pulmonary embolism and deep vein thrombosis. Its poor solubility (5-7µg/mL) and P-gp-mediated efflux from intestinal lining limits the oral application of RXN. This work assessed the impact of liquisolid compact technique in augmenting the solubility and bioavailability of RXN. PEG 400, Avicel PH 200, and Aerosil 200 were used as non-volatile liquid, carrier, and coating material, respectively, to formulate RXN liquid-solid compacts (RXN LSCs). A 32-factor factorial design was used in the optimisation to assess the impacts of factors (load factor and carrier:coating ratio) on the responses (angle of repose and Q30 min). Pre-compression parameters of RXN LSCs suggested adequate flow and compressibility. Optimisation data suggested significant influence of factors on both the responses. Optimised RXN LSC-based tablets showed a significantly higher in vitro dissolution rate than RXN API and Xarelto® tablets due to improved solubility, reduced crystallinity, greater surface area, and enhanced wetting of RXN particles. XRD, DSC, and SEM data supported RXN's amorphization. The cytotoxicity (MTT assay) and permeation studies indicated the nontoxicity of prepared RXN LSC tablets and the role of PEG 400 in inhibiting P-gp. Pharmacokinetic study of RXN LSC-based tablets in Albino Wistar rats exhibited 2.51- and 1.66-times higher AUC in comparison to RXN API and Xarelto® tablets respectively, demonstrating that developed formulation had a greater oral bioavailability. The RXN LSC tablets showed longer bleeding times and higher rates of platelet aggregation than RXN API. Thus, RXN LSC tablets can be considered a facile, scalable technology.

Extraction and Characterization of Cellulose and Microcrystalline Cellulose from Teff Straw and Evaluation of the Microcrystalline Cellulose as Tablet Excipient

ABSTRACT Teff (Eragrostis tef), a grass which belongs to the Family Poaceae, is widely cultivated for its starch-rich grains in Ethiopia, generating large amounts of agricultural byproduct, teff straw. The aim of this study was to isolate and characterize cellulose and microcrystalline cellulose (MCC) from teff straw and evaluate MCC as directly compressible tablet excipient. Cellulose was extracted from teff straw and partially depolymerized to obtain MCC. The physicochemical properties of cellulose and MCC powders were characterized. Yields of cellulose and MCC powder from the raw material were 35.2% and 27.2%, respectively. The samples exhibited type-I crystal lattice and similar infrared spectra with that of Avicel PH-101. The degree of polymerization (DP) and crystallinity index of cellulose were 594.51 and 72.26%, respectively. Whereas, MCC powders showed DP of 241.09–257.38 and crystallinity indexes of 76.45–84.52%. Spray dried MCC was found to be more porous and poorly flowable and had higher moisture content when compared with the oven-dried MCC powder. Tablets prepared from both MCC powders fulfil most of the pharmacopoeial requirements. The spray-dried MCC powder also showed superior compactibility to oven-dried MCC. Teff straw can, therefore, be considered to be an alternative source of cellulose and MCC.

Preparation and Characterization of Bilastine Solid Self-Nanoemulsion using Liquisolid Technique

Background: Supersaturable self-nanoemulsion (S-SNE) is an approach for dealing with low oral bioavailability problems. Bilastine (BL) is a selective H1-antihistamine with a bioavailability of 59%. Objective: To use a liquisolid technique to transform liquid BL S-SNE into powder so that both the S-SNE and liquisolid procedures could be used. Methods: Oleic acid, tween 60, transcutol, and soluplus were used to make the liquid BL-loaded S-SNE that was adsorbed onto the Avicel PH101 and Aerosil 200 admixtures. In vitro dissolution and powder flow characteristics were tested. SEM, DSC, X-ray diffraction, FT-IR analysis, and the average droplet size after dispersion in 0.1N HCl were also utilized to define the best formula's solid state. Results: The best liquid-solid composition, SS-F2, is composed of oleic acid, tween 60, transcutol, soluplus, Avicel 101, and Aerosil 200, with a liquid SNE to Avicel 101 ratio of 1.5:1 and an Avicel 200 to Aerosil 200 ratio of 10:1. SS-F2 displayed good flowability and a significant improvement in drug dissolution, with 100% of the medication released after 60 min compared to 62.27% of the marketed BL tablets. According to the solid-state investigation of formula (SS-F2), BL was shown to be in a solvated state in the solidified nanosystem, with no interactions with the excipient used. It also formed a nanoemulsion with mean droplet sizes of 77.57 nm and a PDI of 0.4178, which was similar to liquid S-SNE. Conclusion: The liquisolid technique is a potential method for solidifying a liquid self-emulsifying system while preserving self-nanoemulsion characteristics and increasing dissolving rate.

A laboratory-scale compression feed screw for characterizing continuous feeding of dense granular materials

Compression feed screws are commonly used in biorefineries for the continuous feeding of biomass feedstock into reactors. Developing methods to assess the feasibility of feeding granular materials in a compression feed screw is critical for reducing solids handling issues during operation. A laboratory-scale compression feed screw has been built to measure critical process parameters of the feeding operation, namely the driving torque and the mass flow rate. The process parameters of two granular materials, microcrystalline cellulose Avicel PH-200 and milled corn stover are measured using the laboratory-scale feeder. The results show that a larger torque is required to feed corn stover than Avicel PH-200, even though the former consists of more compressible particles. Further, the device can capture real-time fluctuations in the process parameters during operation. The laboratory-scale feeder can be used to compare the feeding of different granular materials and the measured parameters can be used to validate predictive models for a compression screw feeding process.

The effect of silica nanoparticles on the dustiness of industrial powders

Industrial powders are prompt to be airborne during processing. High dustiness levels may cause process complications like cross-contamination, product loss and filter clogging while increasing the risk of inhalation, dust explosion and fire. Thus, dustiness is often associated with occupational exposure. Despite this, powder products are usually composed of multiple ingredients with silica nanoparticles (S-NP) systematically added to ease their handling. Surprisingly, the relationship between dustiness and product formulation has not been commonly studied. This work investigates the influence of S-NP, SIPERNAT D10 (SD10), on the dustiness of four industrial powders–Avicel PH102, wheat flour, joint filler, and glass beads–using two standard methods: the rotating drum (EN 15051–2) and the vortex shaker (EN 17199–5). Our results show that the dustiness of mixtures powder + SD10 are statistically higher than those of the powder alone and can reach the levels of SD10. TEM micrographs from airborne particles collected in the vortex shaker showed that SD10 detached from the surface of the powder during aerosolisation, emitting nanometric dust; adding SD10 increases the potential for inhalation exposure during industrial processing and handling. Surface energy analysis by inverse gas chromatography (IGC) leads us to conclude that stronger powder-to-SD10 interactions result in less dust emission.

High-level production of Aspergillus niger prolyl endopeptidase from agricultural residue and its application in beer brewing

BackgroundProlyl endopeptidase from Aspergillus niger (AN-PEP) is a prominent serine proteinase with various potential applications in the food and pharmaceutical industries. However, the availability of efficient and low-cost AN-PEP remains a challenge owing to its low yield and high fermentation cost.ResultsHere, AN-PEP was recombinantly expressed in Trichoderma reesei (rAN-PEP) under the control of the cbh1 promoter and its secretion signal. After 4 days of shaking flask cultivation with the model cellulose Avicel PH101 as the sole carbon source, the extracellular prolyl endopeptidase activity reached up to 16.148 U/mL, which is the highest titer reported to date and the secretion of the enzyme is faster in T. reesei than in other eukaryotic expression systems including A. niger and Komagataella phaffii. Most importantly, when cultivated on the low-cost agricultural residue corn cob, the recombinant strain was found to secret a remarkable amount of rAN-PEP (37.125 U/mL) that is twice the activity under the pure cellulose condition. Furthermore, treatment with rAN-PEP during beer brewing lowered the content of gluten below the ELISA kit detection limit (< 10 mg/kg) and thereby, reduced turbidity, which would be beneficial for improving the non-biological stability of beer.ConclusionOur research provides a promising approach for industrial production of AN-PEP and other enzymes (proteins) from renewable lignocellulosic biomass, which provides a new idea with relevant researchers for the utilization of agricultural residues.

Development of Doxazosin mesylate liquisolid system for improved manufacturing processability and bioavailability: in vitro and in vivo evaluation for tailored hypertension treatment approach with modified dissolution rates

In the present research, an attempt was made to optimize the blends of different carriers Neusiln US2, Avicel PH101, and Fujicalin SG by individually blending with each of coating materials Aerosil 200 and Syloid 244 FP that were proposed to contribute to a modified drug dissolution rates of Doxazosin mesylate (DX) through a liquisolid polymer matrix system. The liquisolid formulations were prepared using selected solvent, carriers, and coats by varying drug to polymer ratios. Further formulations were investigated for pre-compression processability by Heckel plot analysis, elastic recovery studies, and post-compression characteristics. In case of carriers, compared to Avicel PH101 highest flowable values (ф) were observed for Neusilin US2 and Fujicalin SG whereas, for coat these values were highest for Aerosil 200 than Sylloid 244 FP. Liquisolid compact with Fujicalin SG and Aerosil 200 exhibited fast release (FR) of 78% in 20 minutes. The liquisolid compact with Neusilin US2 and Syloid 244 FP exhibited prolonged release (PR) of 60% in 240 minutes. DSC and XRD analysis showed loss of DX crystallinity which was confirmed by SEM analysis indicating DX detention within the liquisolid system, in a molecularly dispersed solubilized form. The in vivo studies of DX liquisolid FR formulation exhibited 1.89 fold increase in the oral bioavailability which was 1.69 fold for DX PR formulation compared to pure DX which demonstrated a promising tailored hypertension treatment approach.

Isolation of Cellulase from Selected Fungal Strains and Its Use for Manufacture Microcrystal Cellulose from Kapuk Cortex (Ceiba Pentandra (L.) Gaertn)

This study aims to obtain cellulase enzymes from selected molds for microcrystalline cellulose preparation from ????-cellulose of kapok cortex. Alpha-cellulose was obtained by biodelignification, and the purified cellulase was obtained from the selected mold. The Microcrystalline cellulose obtained from enzymatic hydrolysis was then identified FTIR and DSC, followed by characterization of microcrystalline cellulose, Particle Size and Distribution Analysis (PSA), and Scanning Electron Microscope-Energy Dispersive X-ray (SEM-EDX), Loss on drying, pH, bulk density, tapped density, and flow rate. Biodelignification produced 14.88% ????-cellulose, Penicillium sp. the selected mold had the highest cellulase activity, with a cellulolytic index of 4.83. FTIR identification was similar to Avicel PH 101 with a melting point of 244.580°C. Loss on drying was 3.74%, pH was 7.0, particle size ranged from 13.06 to 196.79 ????m, bulk density and tapped density were 0.11 g/cm3 and 0.23 g/cm3, respectively flow rate character is quite good. SEM-EDX was showed that the morphological shape of the microcrystalline cellulose of the kapok cortex is elongated. Microcrystalline cellulose has shown a quite similar in character and can be furthered.

PREPARATION OF MICROCRYSTALLINE CELLULOSE FROM DISSOLVING CELLULOSE OBTAINED FROM JUTE FIBERS AND ITS APPLICATION IN THE FORMULATION OF FEXOFENADINE HYDROCHLORIDE TABLET DOSAGE FORM

Introduction: The most affordable tablet form is microcrystalline cellulose (MCC), a popular pharmaceutical excipient that is utilized as a filler or binder in immediately compressible tablets. Methods: In the present study, we extracted dissolving cellulose from jute fibers by treatment with 0.1 N hydrochloric acid solution and 20% w/w sodium hydroxide solution at high temperature and pressure. The dissolving cellulose was subjected to acid hydrolysis at 100 0C for 2 h with 2 N hydrochloric acid. The identity of the MCC was confirmed by FT-IR and by determining the degree of polymerization. To evaluate the flow property, we determined the bulk, density, tapped density, Hausner index, Carr’s index and angle of repose. The tableting property of the prepared MCC was evaluated by making fexofenadine hydrochloride tablets.&#x0D; Result and Discussion: The dissolving cellulose contains 94.67% α-cellulose The DP of the MCC was found 191. The powder properties such as bulk density, tapped density, Hausner index and Carr’s index, angle of repose values are comparable with that of standard Avicel PH102. The hardness, friability, disintegration time and % dissolved in 30 minutes were dissolution value of the tablets 5.6 kg, 0.34%, 178.17 sec and 83.89%, respectively. All these values are within the United State Pharmacopoeia range and are comparable with the tablets prepared from Avicel PH102 and marketed fexofenadine tablets.

Formulation and in vitro Evaluation of Taste-Masked Orodispersible Tablets of Levocetirizine Dihydrochloride

The main aim was to formulate and evaluate and optimize taste- masked orodispersible tablets of Levocetirizine Dihydrochloride, a drug used in Allergic Rhinitis was prepared by direct compression method. The study involved different excipients which were used for the formulation and tested for their compatibility with Levocetirizine Dihydrochloride by the FT-IR studies. Based on the results of FT-IR studies, most of the excipients were found to be compatible with Levocetirizine which was used for the preparation of Levocetirizine oral disintegrating tablets. Levocetirizine Dihydrochloride is bitter in taste so the Tulsian-339 (ion exchange resin) was used to mask the taste to formulate an orodispersible dosage formulation using drug resin complex. Nine batches (F1-F9) of oro dispersible tablets of Levocetirizine Dihydrochloride were prepared by using super disintegrants like Sodium starch glycolate, Avicel PH102 and Low Hydroxy Propyl Cellulose in variable concentrations along with excipients for the development of optimized formulation. All formulations were subjected to evaluation studies of drug content, weight variation, water absorption ratio, wetting time, in vitro disintegration, dispersion time, hardness, friability and thickness uniformity. The tablets were disintegrated in vitro within 28-38 seconds, the complete drug was released from the tablets within 15 min. The results showed that Levocetirizine dihydrochloride was successfully formulated into an orodispersible dosage form.

Variasi Kadar AvicelPH101 dan Aerosil Terhadap Kadar Air Serbuk Bunga Telang (Clitoria ternatea L.)

Abstract&#x0D; &#x0D; Background: Banyuwangi has the potential of diverse natural resources. One example of the potential plant that can be utilized is butterfly pea (Clitoria ternatea L.). The contents of butterfly pea are phenolic acids, stilbenes (phytoalexins), flavanols, anthocyanins, flavonols and flavanones, polyphenols and flavonoids. In this research, preparations were developed from butterfly pea extract into powder form to make it more practical. The problems occur in making formulations usually have physical characteristics of being thick or liquid making it difficult to formulate into solid dosage forms, so in its manufacture additional ingredients or adsorbents were needed to dry the extract so it is easy to formulate. Avicel pH 101 and aerosil is a combination used as an adsorbent in the manufacture of powders. Aim: This study aimed to determine the effect of Avicel PH101 and Aerosil variations through the results of evaluating the moisture content of butterfly pea ethanol extract powder. Method: This study was a laboratory experiment that began with maceration of butterfly pea simplicia using 70% ethanol and then evaporated to obtain a thick extract of butterfly pea. The preparation of butterfly pea powder was carried out using a combination of Avicel pH 101 and aerosil which was varied in four formulas, namely FI (20%:20%), FII (50%:20% ), FIII (90%:0%), FIV (90% :20%) ). Results: The evaluation results of the water content test that met the requirements were FII(50%:20%) with a moisture content of 2.4%, FIII(90%:0%) with a moisture content of 2.8% and FIV (90%;20%) was the most optimal formulation of Avicel PH101 and Aerosil combination for the manufacture of butterfly pea powder with a moisture content of 1.5% and organoleptically in the form of a powder obtained was very dry and delicate.&#x0D; &#x0D; Keywords: Aerosil, Avicel PH101, Butterfly Pea Powder, Moisture Content.&#x0D; &#x0D;

Fabrication and characterization of Orlistat Liquisolid tablets

The aim of the work was to improve the dissolution properties of the practically insoluble anti-obesity drug, Orlistat by utilizing liquisolid technique. Different liquisolid tablets were prepared by dissolving Orlistat in PG with Avicel PH 102 as carrier, Aerosol 200 as coating material and Sodium starch glycolate as disintegrating agent. Additives such as PVP, HPMC and HPG were incorporated into the formulations to improve dissolution characteristics. The formulated liquisolid tablets were evaluated for post compression parameters such as weight variation, hardness, friability, drug content and in-vitro dissolution studies. FT-IR study suggested that there was no chemical interaction between the drug and excipients. DSC was performed to evaluate the physicochemical properties of the liquisolid tablets, which confirm the conversion of crystalline form of the drug to the amorphous form in liquisolid tablets. The result showed that liquisolid formulation of Orlistat exhibited higher percentage of drug release than directly compressed tablets which show significant benefit of liquisolid tablet in increasing wetting properties and surface area of drug available for dissolution.

Influences of Glimepiride Self-Nanoemulsifying Drug Delivery System Loaded Liquisolid Tablets on the Hypoglycemic Activity and Pancreatic Histopathological Changes in Streptozotocin-Induced Hyperglycemic Rats.

The development of an oral anti-diabetic medication characterized by enhanced hypoglycemic activity is in high demand. The goal was to study the hypoglycemic activity and pancreatic histopathology after the black-seed-based self-nanoemulsifying drug delivery system (SNEDDS) loaded with glimepiride liquisolid tablets to diabetic rats. The solubility of glimepiride in various vehicles was investigated. An optimization SNEDDS formulation was developed using a mixture of the experimental design approach. Box-Behnken design (BBD) was used to develop glimepiride liquisolid tablets utilizing Avicel PH 101 and Neusilin as a carrier mixture and FujiSil as a coating material. The quality attributes of the prepared tablets were assessed. Following the administration of the optimized tablets to diabetic rats, the pharmacodynamics and histopathological changes were investigated and compared to a commercial drug product. Results revealed that the optimized SNEDDS formulation that contains 15.43% w/w black seed oil, 40% w/w Tween 80, and 44.57% w/w Polyethylene glycol 400 showed an average droplet size of 34.64 ± 2.01 nm and a drug load of 36.67 ± 3.13 mg/mL. The optimized tablet formulation contained 0.31% Avicel in the carrier mixture, a 14.99 excipient ratio, and 8% superdisintegrant. Pre- and post-compression properties were satisfactory, and the optimized glimepiride liquisolid tablet showed a two-fold increase in dissolution. The optimized tablet demonstrated superior pharmacodynamics. The pancreatic tissues of the group treated with the optimized tablet displayed normal histological structure. The obtained data offered a commercially viable alternative for manufacturing solid dosage forms containing water-insoluble drugs, but additional clinical research is required.

DEM analysis of swelling behaviour in granular media

Many granular materials change their volume as they absorb fluids. This phenomenon is called swelling and can be observed in a variety of solids, such as soils, wood, absorbent hygiene products (AHPs) and pharmaceutical excipients. Therefore, an in-depth understanding of grain swelling is of great importance. Since experimental investigations can often provide only limited information, while great insight could be gained from numerical modelling, rigorous numerical models for predicting particle swelling are required. Hence, the objective of this research is to develop and validate a Discrete Element Method (DEM) for swelling of particles. A first order kinetic model was employed to predict the volume expansion of a single grain and subsequently implemented in DEM. The validation of the model was accomplished by comparing the expansion with time of a packed bed made of super absorbent polymer (SAP) particles obtained numerically and experimentally. It was shown that the DEM model can accurately predict the bed expansion. The model was then employed to simulate the swelling of three different materials: superabsorbent polymer (SAP), rice and microcrystalline cellulose (MCC Avicel PH102). As expected, it is demonstrated that the material properties play a significant role on the swelling; the fastest to reach its maximum expansion is the granular bed made of MCC PH102, followed by SAP and rice. However, the highest swelling capacity is achieved with SAP. Moreover, a preliminary DEM analysis of the segregation in a swelling binary mixture is presented in this work. Results suggest that systems which contain a small number of particles, and thus are looser, are more prone to segregation. Future study could advance the developed model to analyse consequences of swelling phenomena in granular materials, such as segregation and heat generation.

ENHANCING THE SOLUBILITY OF DIPYRIDAMOLE BY LIQUISOLID COMPACTS BASED ON A FACTORIAL DESIGN APPROACH

Dipyridamole is a phosphodiesterase inhibitor used to prevent postoperative thromboembolic events. It is a poorly water-soluble drug with absolute bioavailability of 37-66 %. Water-insoluble drugs still have a poor dissolution rate, one of the biggest problems facing the pharmaceutical industry. To improve the dissolution rate of Dipyridamole, liquisolid compacts were developed in the present study. Liquidsolid formulations were prepared using Peceol, Avicel PH 112, and Aerosil, in different ratios, as a non-volatile solvent, carrier material and coating material respectively. Excipients and drug interactions were characterized through FT-IR. These studies showed no interaction between excipients and drug. 32 factorial design approach was implemented. The formulations were optimized using Design Expert version 13.00 (StatEase Inc., Minneapolis, MN, USA). An optimal formulation exhibited an angle of repose of 25.12°, a hardness of 3.1 kg/cm2 and a percentage cumulative drug release of 99.22 % after 10 minutes. The observed values were found to be similar to the predicted values. Based on these observations, DPY–O can be considered to be the optimum formulation.

SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™.

The study is based on using SeDeM expert system in developing controlled-release tramadol HCl osmotic tablets and its in-silico physiologically based pharmacokinetic (PBPK) modeling for in-vivo pharmacokinetic evaluation. A Quality by Design (QbD) based approach in developing SeDEM-driven full factorial osmotic drug delivery was applied. A 24 Full-factorial design was used to make the trial formulations of tramadol HCl osmotic tablets using NaCl as osmogen, Methocel K4M as rate controlling polymer, and avicel pH 101 as diluent. The preformulation characteristics of formulations (F1-F16) were determined by applying SeDeM Expert Tool. The formulation was optimized followed by in-vivo predictive pharmacokinetic assessment using PBPK “ACAT” model of GastroPlus™. The FTIR results showed no interaction among the ingredients. The index of good compressibility (ICG) values of all trial formulation blends were ≥5, suggesting direct compression is the best-suited method. Formulation F3 and F4 were optimized based on drug release at 2, 10, and 16 h with a zero-order kinetic release (r 2 = 0.992 and 0.994). The SEM images confirmed micropores formation on the surface of the osmotic tablet after complete drug release. F3 and F4 were also stable (shelf life 29.41 and 23.46 months). The in vivo simulation of the pharmacokinetics of the PBPK in-silico model revealed excellent relative bioavailability of F3 and F4 with reference to tramadol HCl 50 mg IR formulations. The SeDeM expert tool was best utilized to evaluate the compression characteristics of selected formulation excipients and their blends for direct compression method in designing once-daily osmotically controlled-release tramadol HCl tablets. The in-silico GastroPlus™ PBPK modeling provided a thorough pharmacokinetic assessment of the optimized formulation as an alternative to tramadol HCl in vivo studies.

An extended 3-compartment model for describing step change experiments in pharmaceutical twin-screw feeders at different refill regimes

Residence time distributions (RTDs) are a valuable tool for product tracking in the unit operations of a continuous line for manufacturing pharmaceutical oral solid dosage (OSD) and the integrated system itself. The first unit operation in such a continuous line in which extended intermixing can occur, is typically a feeder. The RTD of a feeder can be obtained by performing tracer experiments with a tracer material. A physical interpretation can be given to the observed tracer concentration responses by fitting a tanks-in-series (TIS) or compartmental model to it. Consequently, the internal mixing behaviour inside the feeder hopper can be rationalized. However, typically, a constant volume is assumed for the tanks or compartments in these models. This has led to several publications where the experimental set-up does not violate the constant volume assumption, i.e. one performs refills at a high hopper fill level. Here, we step away from this assumption and develop a set of differential equations for a 3-compartment model in order to account for a non-constant volume of the compartments. Moreover, the model distinguishes between a bypass trajectory formed by the agitator inside the feeder and an inner mixing volume, in which the tracer concentration lags on the tracer concentration in the bypass volume. This compartmentalization was inspired by the results obtained in a previous study using a spatial sampling method to assess the tracer concentration throughout the feeder hopper for different experimental runtimes. The developed model successfully describes the step responses for different refill regimes: the standard smooth first order plus dead time response (FOPDT) for a high refill regime and the more complex step response, including dips in the rising phase of the curve, for the low refill regime. As a consequence, a more thorough understanding of the complex mixing behaviour inside the feeder is obtained, which allows for an improved traceability. Next to that, the model delivers enhanced knowledge on the interaction between the residence time and the refill regime. The developed model was fitted to a data set, containing step change experiments for different pharmaceutical materials (Tablettose 80 (T80), Microcelac 100 (MCL), and Avicel PH101 (MCC)), different mass flow rates, and refill regimes. The experimentally observed phenomena could be reliably described by the proposed model. The model showed an improved transferability compared to typical TIS models.

The Role of Excipients in Liquisolid Technology

This article gives criteria for choosing excipients in liquisolid technology. Liquisolid technology is applicable for non polar drugs by converting drug solution into dry free flowing powder. Patient compliance is more in oral route of administration .Numerous techniques like solid dispersion, micronisation, lyophilisation co-grinding, co-precipitation,complexation and nanotechnology are used to increase aqueous solubility Solid dispersion having stability issues while micronization and complexation can cause agglomeration. In Nanotechnology, high cost involved in sophicticated instruments. Liquisolid technology is considered to be one of the best technique to to overcome solubility,dissolution and bioavailability. It convert drug solution into dry free flowing powder. This technique is simple manufacturing process with low production cost. In vitro release is enhanced by using this technology. There is significant role of excipients in this novel technique to get effective release of drug. Associated problems of BCS class II and IV is mostly solved in respect to solubility. Especially carrier with high specific surface area gives good results in overcoming all challenges. Carriers such as Lactose, Starch, Avicel pH101,Fujacilin, Neusilin ,each having specific properties in release of drug. Among all mostly used carriers are Avicel, Fujacilin and Neusilin as with highest Specific Surface Area (SSA) than others. PVP and SSG is considered best disintegrating agent as having good swelling property and flow property as Polyvinypyrrolidine can be used in high dose drugs. With large SSA and high adsorptive property Neusilin, Aerosil , PVP as carrier, coating material and disintegrating agent are considered perfect excipients in liquisolid technology.

Central Composite Design for the Development and Evaluation of Liquisolid Compacts of Glyburide

Abstract: Background: Glyburide is an oral antidiabetic agent with a shorter half-life and is practically insoluble in water. As a result, there is a need to enhance the drug solubility with a aim to improve drug absorption via the oral route. The goal of this study was to formulate, optimize and evaluate the liquisolid tablets of Glyburide using a suitable liquid vehicle in order to enhance the solubility, and bioavailability of the Glyburide. Materials and Methods: The liquisolid compacts of Glyburide were prepared by direct compression method using approved excipients. Using central composite design, the amount of Transcutol HP and carrier: coating ratio to be added in the formulations of Glyburide liquisolid compact has been theoretically generated by the software. The liquisolid tablets were evaluated for thickness and diameter, hardness, weight variation, friability, content uniformity, disintegration time, in-vitro dissolution study and compared with marketed product. Results: The prepared liquisolid system exhibited good flow-properties. The allpost compression parameters were well within the specified limits. The release profile of optimal formulation revealed higher drug release compared to marketed formulation. Increases in the concentration of liquid vehicle and carrier: coating material ratio resulted in an increase in the dissolution rate. Conclusion: The liquisolid compact method was discovered to be a potential method to enhance the dissolution profile, thereby enhancing the solubility of the Glyburide. Key words: Liquisolid technique, Glyburide, Central composite design, Aerosil200, Transcutol HP, Avicel PH-102.