Effect of different gelators on the physicochemical properties and microstructure of coconut oleogels.

BACKGROUND: The inherent properties of coconut oil (CO), including its elevated saturated fatty acid content and low melting point, make it suitable for application in plastic fat processing. The present study explores the physicochemical characteristics, micromorphology and oxidative stability of oleogels produced from CO using various gelators [ethylcellulose (EC), ß-sitosterol/γ-oryzanol (PS) and glyceryl monostearate (MG)] to elucidate the formation mechanisms of coconut oleogels (EC-COO, PS-COO and MG-COO). RESULTS: Three oleogel systems exhibited a solid-like behavior, with the formation of crystalline forms dominated by ß and ß'. Among them, PS-COO exhibited enhanced capability with respect to immobilizing liquid oils, resulting in solidification with high oil-binding capacity, moderate hardness and good elasticity. By contrast, MG-COO demonstrated inferior stability compared to PS-COO and EC-COO. Furthermore, MG-COO and PS-COO demonstrated antioxidant properties against CO oxidation, whereas EC-COO exhibited the opposite effect. PS-COO and EC-COO exhibited superior thermodynamic behavior compared to MG-COO. CONCLUSION: Three oleogels based on CO were successfully prepared. The mechanical strength, storage modulus and thermodynamic stability of the CO oleogel exhibited concentration dependence with increasing gelling agent addition. PS-COO demonstrated relatively robust oil-binding capacity and oxidative stability, particularly with a 15% PS addition. This information contributes to a deeper understanding of CO-based oleogels and offers theoretical insights for their application in food products. © 2024 Society of Chemical Industry.

Natural resin as a biosource and bio-based plasticizer for edible resin/ethylcellulose composite film preparation.

Nowadays, finding natural and inexpensive resources that can be easily used to make food films has been considered. Despite the widespread use of synthetic resins, natural resins are rarely used. Opopanax resin (OR) was used in this study as a new biosource to prepare the hydrophobic edible film. Ethylcellulose (EC) was blended well with the resin, allowing the formation of a composite film. Film preparation was possible using different amounts of OR and EC. It was interesting that OR had a plasticizing effect on EC film. While using up to 33% w/w glycerol could not produce an elastic EC film, using only 8.5% w/w OR produced a stiff and flexible EC film with lower water sensitivity. Fourier transform infrared (FTIR) spectroscopy analysis showed that the strength of C-O-C and CH bonds in OR + EC film was higher than in EC film. Despite the higher water sensitivity of OR-based composite films than EC-based composite films, they had lower water vapor permeability (WVP) and higher contact angle due to their smoother and more homogeneous film structures with lower porosity, confirmed by scanning electron microscopy (SEM) images. The mechanical properties showed that the film with the highest resin content had the lowest tensile strength (~ 0.4 MPa) and the higher elongation at break (~ 67%) and, therefore, the highest flexibility. The use of natural resins as a biosource is a promising approach in food packaging to prepare hydrophobic films with desirable mechanical properties.

Ethylcellulose-stabilized fat-tissue phantom for quality assurance in clinical hyperthermia.

BACKGROUND: Phantoms accurately mimicking the electromagnetic and thermal properties of human tissues are essential for the development, characterization, and quality assurance (QA) of clinically used equipment for Hyperthermia Treatment (HT). Currently, a viable recipe for a fat equivalent phantom is not available, mainly due to challenges in the fabrication process and fast deterioration. MATERIALS AND METHODS: We propose to employ a glycerol-in-oil emulsion stabilized with ethylcellulose to develop a fat-mimicking material. The dielectric, rheological, and thermal properties of the phantom have been assessed by state-of-the-art measurement techniques. The full-size phantom was then verified in compliance with QA guidelines for superficial HT, both numerically and experimentally, considering the properties variability. RESULTS: Dielectric and thermal properties were proven equivalent to fat tissue, with an acceptable variability, in the 8 MHz to 1 GHz range. The rheology measurements highlighted enhanced mechanical stability over a large temperature range. Both numerical and experimental evaluations proved the suitability of the phantom for QA procedures. The impact of the dielectric property variations on the temperature distribution has been numerically proven to be limited (around 5%), even if higher for capacitive devices (up to 20%). CONCLUSIONS: The proposed fat-mimicking phantom is a good candidate for hyperthermia technology assessment processes, adequately representing both dielectric and thermal properties of the human fat tissue while maintaining structural stability even at elevated temperatures. However, further experimental investigations on capacitive heating devices are necessary to better assess the impact of the low electrical conductivity values on the thermal distribution.

Nanoemulsion-Based Multilayer Films for Ground Beef Preservation: Antimicrobial Activity and Physicochemical Properties.

This study aimed to improve the physical, mechanical, and biological properties of a monolayer pectin (P) film containing nanoemulsified trans-Cinnamaldehyde (TC) by incorporating it between inner and outer layers of ethylcellulose (EC). The nanoemulsion had an average size of 103.93 nm and a zeta potential of -46 mV. The addition of the nanoemulsion increased the opacity of the film, reduced its moisture absorption capacity, and improved its antimicrobial activity. However, the tensile strength and elongation at break of the pectin films decreased after the incorporation of nanoemulsions. Multilayer films (EC/P/EC) showed a higher resistance to breaking and better extensibility compared to monolayer films. The antimicrobial activity of both mono and multilayer films was effective in inhibiting the growth of foodborne bacteria during storage of ground beef patties at 8 °C for 10 days. This study suggests that biodegradable antimicrobial multilayer packaging films can be effectively designed and applied in the food packaging industry.

Antibacterial and Antifungal Silver Nanoparticles with Tunable Size Embedded in Various Cellulose-Based Matrices.

The aim of this study was to synthesize silver nanoparticles (AgNPs) using cellulose derivatives and to evaluate their antimicrobial potential. As effective reducing and stabilizing agents for AgNPs, cellulose derivatives, such as hydroxypropyl cellulose (HPC), methylcellulose (MC), ethylcellulose (EC), and cellulose acetate (CA), were used. Their ability to reduce silver ions as well as the size of the resulting AgNPs were compared. The formation and stability of the reduced AgNPs in the solution were monitored using UV-Vis analysis. The size, morphology, and charge of the AgNPs were evaluated. We found that, when using cellulosic derivatives, AgNPs with sizes ranging from 17 to 89 nm and different stabilities were obtained. The parameters, such as size and ζ potential indicate the stability of AgNPs, with AgNPs-CA and AgNPs-HPC being considered more stable than AgNPs-EC and AgNPs-MC since they show higher ζ potential values. In addition, the AgNPs showed antimicrobial activity against all reference strains and clinical isolates. MIC values between 0.0312 and 0.125 mM had a bactericidal effect on both Gram-positive and Gram-negative bacteria. The fungicidal effect was obtained at a MIC value of 0.125 mM. These results may provide rational support in the design of medical gauze products, including gauze pads, rolls, and sponges.

Abemaciclib-loaded ethylcellulose based nanosponges for sustained cytotoxicity against MCF-7 and MDA-MB-231 human breast cancer cells lines.

Abemaciclib (AC) is a novel, orally available drug molecule approved for the treatment of breast cancer. Due to its low bioavailability, its administration frequency is two to three times a day that can decrease patient compliance. Sustained release formulation are needed for prolong the action and to reduce the adverse effects. The aim of current study was to develop sustained release NSs of AC. Nanosponges (NSs) was prepared by emulsion-solvent diffusion method using ethyl-cellulose (EC) and Kolliphor P-188 (KP-188) as sustained-release polymer and surfactant, respectively. Effects of varying surfactant concentration and drug: polymer proportions on the particle size (PS), polydispersity index (PDI), zeta potential (ζP), entrapment efficiency (%EE), and drug loading (%DL) were investigated. The results of AC loaded NSs (ACN1-ACN5) exhibited PS (366.3-842.2 nm), PDI (0.448-0.853), ζP (-8.21 to -19.7 mV), %EE (48.45-79.36%) and %DL (7.69-19.17%), respectively. Moreover, ACN2 showed sustained release of Abemaciclib (77.12 ± 2.54%) in 24 h Higuchi matrix as best fit kinetics model. MTT assay signified ACN2 as potentials cytotoxic nanocarrier against MCF-7 and MDA-MB-231 human breast cancer cells. Further, ACN2 displayed drug release property without variation in the % release after exposing the product at 25 °C, 5 °C, and 45 °C storage conditions for six months. This investigation proved that the developed NSs would be an efficient carrier to sustain the release of AC in order to improve efficacy against breast cancer.

Development of Antimicrobial Laser-Induced Photodynamic Therapy Based on Ethylcellulose/Chitosan Nanocomposite with 5,10,15,20-Tetrakis(m-Hydroxyphenyl)porphyrin.

The development of new antimicrobial strategies that act more efficiently than traditional antibiotics is becoming a necessity to combat multidrug-resistant pathogens. Here we report the efficacy of laser-light-irradiated 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrin (mTHPP) loaded onto an ethylcellulose (EC)/chitosan (Chs) nanocomposite in eradicating multi-drug resistant Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans. Surface loading of the ethylcelllose/chitosan composite with mTHPP was carried out and the resulting nanocomposite was fully characterized. The results indicate that the prepared nanocomposite incorporates mTHPP inside, and that the composite acquired an overall positive charge. The incorporation of mTHPP into the nanocomposite enhanced the photo- and thermal stability. Different laser wavelengths (458; 476; 488; 515; 635 nm), powers (5-70 mW), and exposure times (15-45 min) were investigated in the antimicrobial photodynamic therapy (aPDT) experiments, with the best inhibition observed using 635 nm with the mTHPP EC/Chs nanocomposite for C. albicans (59 ± 0.21%), P. aeruginosa (71.7 ± 1.72%), and S. aureus (74.2 ± 1.26%) with illumination of only 15 min. Utilization of higher doses (70 mW) for longer periods achieved more eradication of microbial growth.

Physicochemical properties of beef burger after partial incorporation of ethylcellulose oleogel instead of animal fat.

The aim of this study was to evaluate the physicochemical properties of beef burger after substitution of animal fat with the ethylcellulose (EC) oleogel. Therefore, sesame oil oleogels were prepared using EC in concentrations of 10%, and cooled at 25 °C. The fatty acid profile of EC oleogel compared with animal fat. Then, the EC oleogel was incorporated to hamburger at the 0, 25 and 50% instead of animal fat and color and textural properties as well as cooking loss, cooking shrinkage, fat absorption, and lipid oxidation of the beef burgers were evaluated. As an outcome, the EC oleogel contained high levels of linoleic and linolenic acids, while the palmitic and stearic acids were lower than the animal fats, and myristic acid was not detectable. Replacement of animal fat with EC oleogel upgraded the quality of final product by reducing cooking loss and fat absorption. Production of beef burger with EC oleogel decreased the oxidation process during frozen storage as well as cooking loss and fat absorption, and enhanced textural properties including chewiness and hardness. Improvement of nutritional and technological properties of hamburgers contained EC oleogel makes it a desirable candidate for animal fat substitution. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at(10.1007/s13197-021-04970-4).

Bio-Based Nanoparticles as a Carrier of ß-Carotene: Production, Characterisation and In Vitro Gastrointestinal Digestion.

ß-carotene loaded bio-based nanoparticles (NPs) were produced by the solvent-displacement method using two polymers: zein and ethylcellulose. The production of NPs was optimised through an experimental design and characterised in terms of average size and polydispersity index. The processing conditions that allowed to obtain NPs (<100 nm) were used for ß-carotene encapsulation. Then ß-carotene loaded NPs were characterised in terms of zeta potential and encapsulation efficiency. Transmission electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction analysis were performed for further morphological and chemical characterisation. In the end, a static in vitro digestion following the INFOGEST protocol was performed and the bioaccessibility of ß-carotene encapsulated in both NPs was determined. Results show that the best conditions for a size-controlled production with a narrow size distribution are lower polymer concentrations and higher antisolvent concentrations. The encapsulation of ß-carotene in ethylcellulose NPs resulted in nanoparticles with a mean average size of 60 ± 9 nm and encapsulation efficiency of 74 ± 2%. ß-carotene loaded zein-based NPs resulted in a mean size of 83 ± 8 nm and encapsulation efficiency of 93 ± 4%. Results obtained from the in vitro digestion showed that ß-carotene bioaccessibility when encapsulated in zein NPs is 37 ± 1%, which is higher than the value of 8.3 ± 0.1% obtained for the ethylcellulose NPs.

Exploring the Potential of Hydrophilic Matrix Combined with Insoluble Film Coating: Preparation and Evaluation of Ambroxol Hydrochloride Extended Release Tablets.

To explore the potential utility of combination of hydrophilic matrix with membrane-controlled technology, the present study prepared tablets of a water-soluble model drug (ambroxol hydrochloride), through process of direct compression and spray coating. Single-factor experiments were accomplished to optimize the formulation. In vivo pharmacokinetics was then performed to evaluate the necessity and feasibility of further development of this simple process and low-cost approach. Various release rates could be easily obtained by adjusting the viscosity and amount of hypromellose, pore-former ratios in coating dispersions and coating weight gains. Dissolution profiles of coated tablets displayed initial delay, followed by near zero-order kinetics. The pharmacokinetic study of different formulations showed that lag time became longer as the permeability of coating membrane decreased, which was consistent with the in vitro drug release trend. Besides, in vitro/in vivo correlation study indicated that coated tablets exhibited a good correlation between in vitro release and in vivo absorption. The results, therefore, demonstrated that barrier-membrane-coated matrix formulations were extremely promising for further application in industrialization and commercialization.

Double-coated pellets with semipermeable ethylcellulose coating for detection of cholinesterase inhibitors.

Currently, nerve agents are often used in terrorist attacks or assassinations. In such cases, it is necessary to detect them quickly, accurately and easily right in the field. Detection tubes, which are small devices containing pellets with immobilized cholinesterase and detection reagents, meet these conditions. Their detection mechanism is based on a highly sensitive enzymatic Ellman reaction, when in the absence of cholinesterase inhibitors the pellets develop a visible yellow color, whereas in their presence the carriers retain the original color. The rate of reaction, its sensitivity and the distinct color transition are the key points of the research. In this experiment, double-coated pellets were prepared. The first coating contained the butyrylcholinesterase immobilized in hypromellose, while the second coating consisted of ethylcellulose and triethyl citrate. Based on the properties of such carriers, samples containing lactose dispersed in the ethylcellulose coating were also prepared, which was expected to have an effect on increasing the permeability of the coating and hence the detection rate and color intensity. In addition to selected physicochemical properties, carriers were evaluated for enzyme activity, sensitivity and color transition intensity. Samples showing the best properties were subjected to a 24-months stability test at three different temperatures and humidity.

Use of extrusion aids for successful production of Kollidon® CL-SF pellets by extrusion-spheronization.

OBJECTIVE: Fine particle ethylcellulose (FPEC) or poly(ethylene oxide) (PEO) addition to a Kollidon CL-SF was investigated to address low yield and poor sphericity in extruded-spheronized pellets. SIGNIFICANCE: The success of crospovidone as a diluent in extrusion-spheronization was dependent on a small particle size of the polymer. FPEC aided production of rugged and spherical pellets using a large particle size grade, Polyplasdone® XL. PEO acted as an extrusion-spheronization aid when ethylcellulose was the diluent. These extrusion-spheronization aids could serve in this role when Kollidon® CL-SF (K CL-SF) is the diluent. METHODS: The influence of formulation and process variables on pellet properties was investigated using design of experiments. A planetary mixer was used to prepare powder blends and the wetted mass after addition of water. An EXD 60 extruder produced extrudate that was spheronized in a Q230 marumerizer. Wet pellets were dried in a forced-air oven. RESULTS: FPEC improved rounding up but reduced pellet yield. Poly(ethylene oxide) imparted desired characteristics to the wetted mass, the extrudate, and the spheronized pellets. Pellet average diameter, yield, sphericity, aspect ratio, friability, and dissolution profile were assessed. Equations for pellet characteristics facilitated discussion of the influences of factors and their interactions. Optimization was performed on pellets that included PEO. CONCLUSIONS: PEO proved to be an exceptional extrusion-spheronization aid in the preparation of pellets using K CL-SF. It facilitated wetted mass extrusion with minimal mass loss to the extruder, and markedly improved the sphericity of the pellets produced by marumerization. Immediate release pellets were obtained.

Multivariate analysis as a method to understand variability in a complex excipient, and its contribution to formulation performance.

A key part of the Risk Assessment of excipients is to understand how raw material variability could (or does) contribute to differences in performance of the drug product. Here we demonstrate an approach which achieves the necessary understanding for a complex, functional, excipient. Multivariate analysis (MVA) of the certificates of analysis of an ethylcellulose aqueous dispersion (Surelease) formulation revealed low overall variability of the properties of the systems. Review of the scores plot to highlight batches manufactured using the same ethylcellulose raw material in the formulation, indicated that these batches tend to be more closely related than other randomly selected batches. This variability could result in potential differences in the quality of drug product lots made from these batches. Manufacture of a model drug product from Surelease batches coated using different lots of starting material revealed small differences in the release of a model drug, which could be detected by certain model dependent dissolution modeling techniques, but they were not observed when using model-independent techniques. This illustrates that the techniques are suitable for detecting and understanding excipient variability, but that, in this case, the product was still robust.

Cellulose Acetate Butyrate: Ammonio Methacrylate Copolymer Blends as a Novel Coating in Osmotic Tablets.

The objective of this work was the preparation of osmotic tablets using polymer blends of cellulose acetate butyrate (CAB) or ethylcellulose with ammonio methacrylate copolymer (Eudragit® RL). The advantage of these coatings in comparison to the traditionally used cellulose acetate is their solubility in safer organic solvents like ethanol. Polymer films were characterized with respect to their water uptake, dry mass loss, and mechanical properties. The effect of the polymer blend ratio on drug release and on the rupture force of the coating was investigated. In addition, the effect of drug solubility and content, pH and agitation rate of the release medium, and coating level and plasticizer content on the release were studied. With increased Eudragit® RL content in the coating blends, higher medium uptake of the film was observed, resulting in shorter lag times and faster drug release from the osmotic tablets. Replacing ethylcellulose with cellulose acetate butyrate as a coating material led to shorter lag times and faster drug release due to increased film permeability. In addition, CAB-based films had a higher strength and flexibility. The drug release was osmotically controlled and decreased with increasing coating level. It increased with increased drug solubility, plasticizer content, change of buffer species (acetate > phosphate), and decreased coating level. Agitation rate and drug content had no effect on the drug release. A 20% w/w coating level was sufficient for the tablet to tolerate forces of more than five times of the gastric destructive force reported in literature.

A Novel Approach for Dry Powder Coating of Pellets with Ethylcellulose. Part II: Evaluation of Caffeine Release.

The objective of this study was to assess the efficacy and the capability of a novel ethylcellulose-based dry-coating system to obtain prolonged and stable release profiles of caffeine-loaded pellets. Lauric and oleic acids at a suitable proportion were used to plasticize ethylcellulose. The effect of coating level, percentage of drug loading, inert core particle size, and composition of the coating formulation including the anti-sticking agent on the drug release profile were fully investigated. A coating level of 15% w/w was the maximum layered amount which could modify the drug release. The best controlled drug release was obtained by atomizing talc (2.5% w/w) together with the solid plasticizer during the dry powder-coating process. SEM pictures revealed a substantial drug re-crystallization on the pellet surface, and the release studies evidenced that caffeine diffused through the plasticized polymer acting as pore former. Therefore, the phenomenon of caffeine migration across the coating layer had a strong influence on the permeability of the coating membrane. Comparing dry powder-coated pellets to aqueous film-coated ones, drug migration happened during storage, though more sustained release profiles were obtained. The developed dry powder-coating process enabled the production of stable caffeine sustained release pellets. Surprisingly, the release properties of the dry-coated pellets were mainly influenced by the way of addition of talc into the dry powder-coating blend and by the drug nature and affinity to the coating components. It would be interesting to study the efficacy of novel coating system using a different API.

Comparing a Statistical Model and Bayesian Approach to Establish the Design Space for the Coating of Ciprofloxacin HCl Beads at Different Scales of Production.

The primary objective of this study was to compare two methods for establishing a design space for critical process parameters that affect ethylcellulose film coating of multiparticulate beads and assess this design space validity across manufacturing scales. While there are many factors that can affect film coating, this study will focus on the effects processing conditions have on the quality and extent of film formation, as evaluated by their impact coating yield and drug release. Ciprofloxacin HCl layered beads were utilized as an active substrate core, ethylcellulose aqueous dispersion as a controlled release polymer, and triethyl citrate as a plasticizer. Thirty experiments were conducted using a central composite design to optimize the coating process and map the response surface to build a design space using either statistical least squares or a Bayesian approach. The response surface was fitted using a linear two-factor interaction model with spraying temperature, curing temperature, and curing time as significant model terms. The design spaces established by the two approaches were in close agreement with the statistical least squares approach being more conservative than the Bayesian approach. The design space established for the critical process parameters using small-scale batches was tested using scale-up batches and found to be scale-independent. The robustness of the design space was confirmed across scales and was successfully utilized to establish process signature for the coating process.

Near-infrared-actuated devices for remotely controlled drug delivery.

A reservoir that could be remotely triggered to release a drug would enable the patient or physician to achieve on-demand, reproducible, repeated, and tunable dosing. Such a device would allow precise adjustment of dosage to desired effect, with a consequent minimization of toxicity, and could obviate repeated drug administrations or device implantations, enhancing patient compliance. It should exhibit low off-state leakage to minimize basal effects, and tunable on-state release profiles that could be adjusted from pulsatile to sustained in real time. Despite the clear clinical need for a device that meets these criteria, none has been reported to date to our knowledge. To address this deficiency, we developed an implantable reservoir capped by a nanocomposite membrane whose permeability was modulated by irradiation with a near-infrared laser. Irradiated devices could exhibit sustained on-state drug release for at least 3 h, and could reproducibly deliver short pulses over at least 10 cycles, with an on/off ratio of 30. Devices containing aspart, a fast-acting insulin analog, could achieve glycemic control after s.c. implantation in diabetic rats, with reproducible dosing controlled by the intensity and timing of irradiation over a 2-wk period. These devices can be loaded with a wide range of drug types, and therefore represent a platform technology that might be used to address a wide variety of clinical indications.

Rheological Characterization of Ethylcellulose-Based Melts for Pharmaceutical Applications.

Rheological characterization of ethylcellulose (EC)-based melts intended for the production, via micro-injection moulding (µIM), of oral capsular devices for prolonged release was carried out. Neat EC, plasticized EC and plasticized EC containing solid particles of a release modifier (filler volume content in the melt around 30%) were examined by capillary and rotational rheometry tests. Two release modifiers, differing in both chemical nature and particle geometry, were investigated. When studied by capillary rheometry, neat EC appeared at process temperatures as a highly viscous melt with a shear-thinning characteristic that progressively diminished as the apparent shear rate increased. Thus, EC as such could not successfully be processed via µIM. Plasticization, which induces changes in the material microstructure, enhanced the shear-thinning characteristic of the melt and reduced considerably its elastic properties. Marked wall slip effects were noticed in the capillary flow of the plasticized EC-based melts, with or without release modifier particles. The presence of these particles brought about an increase in viscosity, clearly highlighted by the dynamic experiments at the rotational rheometer. However, it did not impair the material processability. The thermal and rheological study undertaken would turn out a valid guideline for the development of polymeric materials based on pharma-grade polymers with potential for new pharmaceutical applications of µIM.

A Systematic Approach of Employing Quality by Design Principles: Risk Assessment and Design of Experiments to Demonstrate Process Understanding and Identify the Critical Process Parameters for Coating of the Ethylcellulose Pseudolatex Dispersion Using Non-Conventional Fluid Bed Process.

The goal of this study was to utilize risk assessment techniques and statistical design of experiments (DoE) to gain process understanding and to identify critical process parameters for the manufacture of controlled release multiparticulate beads using a novel disk-jet fluid bed technology. The material attributes and process parameters were systematically assessed using the Ishikawa fish bone diagram and failure mode and effect analysis (FMEA) risk assessment methods. The high risk attributes identified by the FMEA analysis were further explored using resolution V fractional factorial design. To gain an understanding of the processing parameters, a resolution V fractional factorial study was conducted. Using knowledge gained from the resolution V study, a resolution IV fractional factorial study was conducted; the purpose of this IV study was to identify the critical process parameters (CPP) that impact the critical quality attributes and understand the influence of these parameters on film formation. For both studies, the microclimate, atomization pressure, inlet air volume, product temperature (during spraying and curing), curing time, and percent solids in the coating solutions were studied. The responses evaluated were percent agglomeration, percent fines, percent yield, bead aspect ratio, median particle size diameter (d50), assay, and drug release rate. Pyrobuttons® were used to record real-time temperature and humidity changes in the fluid bed. The risk assessment methods and process analytical tools helped to understand the novel disk-jet technology and to systematically develop models of the coating process parameters like process efficiency and the extent of curing during the coating process.

Investigation into the Effect of Ethylcellulose Viscosity Variation on the Drug Release of Metoprolol Tartrate and Acetaminophen Extended Release Multiparticulates-Part I.

Ethylcellulose is one of the most commonly used polymers to develop reservoir type extended release multiparticulate dosage forms. For multiparticulate extended release dosage forms, the drug release is typically governed by the properties of the barrier membrane coating. The ICH Pharmaceutical Development Guideline (ICH Q8) requires an understanding of the influence of critical material attributes and critical process parameters on the drug release of a pharmaceutical product. Using this understanding, it is possible to develop robust formulations with consistent drug release characteristics. Critical material attributes for ethylcellulose were evaluated, and polymer molecular weight variation (viscosity) was considered to be the most critical attribute that can impact drug release. To investigate the effect of viscosity variation within the manufacturer's specifications of ethylcellulose, extended release multiparticulate formulations of two model drugs, metoprolol tartrate and acetaminophen, were developed using ETHOCEL™ as the rate controlling polymer. Quality by Design (QbD) samples of ETHOCEL Std. 10, 20, and 100 Premium grades representing the low, medium, and high molecular weight (viscosity) material were organically coated onto drug layered multiparticulates to a 15% weight gain (WG). The drug release was found to be similar (f 2 > 50) for both metoprolol tartrate and acetaminophen multiparticulates at different coating weight gains of ethylcellulose, highlighting consistent and robust drug release performance. The use of ETHOCEL QbD samples also serves as a means to develop multiparticulate dosage formulations according to regulatory guidelines.