The purpose of this work was to develop a practical scale-up model for a solvent-based pan-coating process. Practical scale-up rules to determine the key parameters (pan load, pan speed, spray rate, air flow) required to control the process are proposed. The proposed scale-up rules are based on a macroscopic evaluation of the coating process. Implementation of these rules does not require complex experimentation or prediction of model parameters. The proposed scale-up rules were tested by conducting coating scale-up and scale-down experiments on 24-inch and 52-inch Vector Hi-coaters. The data demonstrate that using these rules led to similar cumulative drug release profiles (f2 >> 50; and P Analysis of Variance [PANOVA] >> 0.05 for cumulative percentage of drug released after 12 hours [Cum12]) from tablets made at 24- and 52-inch scales. Membrane characteristics such as opacity and roughness were also similar across the 2 scales.
The aim of the present study was to prepare surfactant-free pseudolatexes of various methacrylic acid copolymers. These aqueous colloidal dispersions of polymeric materials for oral administration are intended for film coating of solid dosage forms or for direct manufacturing of nanoparticles. Nanoparticulate dispersions were produced by an emulsification-diffusion method involving the use of partially water-miscible solvents and the mutual saturation of the aqueous and organic phases prior to the emulsification in order to reduce the initial thermodynamic instability of the emulsion. Because of the self-emulsifying properties of the methacrylic acid copolymers, it was possible to prepare aqueous dispersions of colloidal size containing up to 30% wt/vol of Eudragit RL, RS, and E using 2-butanone or methyl acetate as partially water-miscible solvents, but without any surfactant.
The purpose of this study was to investigate the effects of particle shape on the movement of particles in a pan-coating device using novel video-imaging techniques. An area scan CCD camera was installed inside a 24-in pan coater at the same location as that of a spray nozzle, and the movement of particles was tracked using machine vision. A white tracer particle was introduced inside a bed of black-coated particles. The effects of pan loading, pan speed, and particle shape on the movement of particles was studied. The response variables were circulation time, surface time, projected area of particle per pass, dynamic angle of repose, cascading velocity, and dispersion coefficient. Experiments were conducted at 3 different pan speeds, 6, 9, and 12 rpm, and 2 fill levels (ratio of bed depth to pan diameter), one eighth and one quarter, and data were collected over a 30-minute time period.
Aqueous film coating is widely used within the pharmaceutical industry to apply either protection or functional coatings on tablets. Especially for functional coatings, smooth and homogeneous films are necessary to ensure the desired functionality. Several film-coating defects can occur as a result of improper drying conditions. Primarily cratering and sticking lead to defects that might be attributed to insufficient drying conditions. If the drying conditions are excessive, blistering or pinholes in the coating film might be observed.1 In addition, insufficient drying conditions can lead to a decomposition of the active substance. This decomposition is usually a result of high temperature or high water content in the core. These undesirable effects display the necessity of optimizing the drying process. In different studies, the influence of inlet air temperature and humidity, air-flow rate, and spray rate on the quality of the product were investigated.
The purpose of this study was to evaluate the change of surface roughness and the development of the film during the film coating process using laser profilometer roughness measurements, SEM imaging, and energy dispersive X-ray (EDX) analysis. Surface roughness and texture changes developing during the process of film coating tablets were studied by noncontact laser profilometry and scanning electron microscopy (SEM). An EDX analysis was used to monitor the magnesium stearate and titanium dioxide of the tablets. The tablet cores were film coated with aqueous hydroxypropyl methylcellulose, and the film coating was performed using an instrumented pilot-scale side-vented drum coater. The SEM images of the film-coated tablets showed that within the first 30 minutes, the surface of the tablet cores was completely covered with a thin film.
Drug Delivery Technology
Vol. 5 No. 9 · October 2005
© Drug Delivery Technology
Roland Bodmeier, PhD, and James W. McGinity, PhD, demonstrate the dry powder coating process to be an efficient method for film-coating tablets with acrylic and cellulosic polymers and as an effective technology to control drug release.
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The objective of this study was to investigate the anion-controlled drug release mechanism through the cationic coating polymer Eudragit RS 30 D as a function of the anion attraction toward the polymer’s quarternary ammonium group (QAG), anion valence, and film composition. The mechanism was investigated by dissolution testing, determination of chloride ion exchange using ion chromatography, plasticizer leaching by means of differential scanning calorimetry, and water uptake by Karl Fischer titration. All experiments were performed on coated theophylline micro tablets or isolated films of various compositions using 0.01 M sodium nitrate, sodium sulfate, disodium succinate, sodium acetate, and succinic acid as dissolution media. The mechanism of drug release involved an immediate penetration of dissolution medium into the polymer followed by an instant exchange of chloride against the medium’s anion species at completely different rates compared with the drug release.
AbstractAn instrumentation and automation system for a side-vented pan coater with a novel air-flow rate measurement system for monitoring the film-coating process of tablets was designed and tested. The instrumented coating system was tested and validated by film-coating over 20 pilot-scale batches of tablets with aqueous-based hydroxypropyl methylcellulose (HPMC). Thirteen different process parameters were continuously measured and monitored, and the most significant ones were logged for analysis. Laser profilometry was used to measure the surface roughness of the coated tablets. The instrumentation system provided comprehensive and quantitative information on the process parameters monitored. The measured process parameters and the responses of the film-coated tablet batches showed that the coating process is reproducible. The inlet air-flow rate influenced the coating process and the subsequent quality of the coated tablets.
AbstractA newly available polyvinylacetate aqueous dispersion, Kollicoat SR 30D, was evaluated with respect to its ability to modulate the in vitro release of a highly water-soluble model compound (diphenhydramine hydrochloride) from nonpareil-based systems. Kollicoat SR 30D premixed with a selected plasticizer (10% wt/wt propylene glycol, 2.5% triethyl citrate, or 2.5% dibutyl sebacate), talc, and red #30 lake dye was coated onto the drug beads in an Aeromatic Strea I fluid-bed drier with a Wurster insert using bottom spray. With propylene glycol as the plasticizer, increases in polymer coating level retarded drug release from beads in a stepwise fashion along with apparent permeability, indicating a consistent release mechanism. Stability studies at 40°C/75% RH revealed gradual decreases in dissolution rate, and additional curing studies further confirmed the dependence of release kinetics on curing condition.
The effects of filler used in the pellet cores (ie, waxy cornstarch or lactose) and the enteric film coat thickness on the diffusion and dissolution of a freely soluble drug were studied. Two kinds of pellet cores containing riboflavin sodium phosphate as a model drug, microcrystalline cellulose (MCC) as a basic filler, and waxy cornstarch or lactose as a cofiller were film coated (theoretically weight increase 20% or 30%) with an aqueous dispersion of cellulose acetate phthalate (CAP). The diffusion of riboflavin sodium phosphate in aqueous enteric-coated pellets was investigated using noninvasive confocal laser scanning microscopy (CLSM). The in vitro release tests were performed using a USP apparatus I (basket method). Diffusion of drug from the core to the film coat was found to be greater with lactose-containing pellets than with waxy cornstarch-containing pellets.
The film forming and coating properties of Glycerol ester of maleic rosin (GMR) and Pentaerythritol ester of maleic rosin (PMR) were investigated. The 2 rosin-based biomaterials were initially characterized in terms of their physicochemical properties, molecular weight (Mw), and glass transition temperature (Tg). Films were produced by solvent evaporation technique on a mercury substrate. Dibutyl sebacate plasticized and nonplasticized films were characterized by mechanical (tensile zzzz strength, percentage elongation, and Young's modulus), water vapor transmission (WVT), and moisture absorption parameters. Plasticization was found to increase film elongation and decrease the Young's modulus, making the films more flexible and thereby reducing the brittleness. Poor rates of WVT and percentage moisture absorption were demonstrated by various film formulations.
The purpose of this study was to evaluate tablet mixing within side-vented coating equipment by assessing the development of color uniformity during coating. A colorimetric method was used to evaluate the time for uniform coating for different mixing baffle systems at different scales of equipment. The influence of tablet size was also determined. The inclusion of rabbit ear baffles in the small-scale equipment reduced the time to achieve color uniformity by 20 minutes. The design of baffle influenced the time for uniform color with a mixing efficiency rank order of tubular > ploughshare > rabbit ear. Upon scale-up, the efficiency of mixing seen at development scale remained equivalent in terms of the influence of baffle design.
The specific aim of the present study was to investigate the biodegradation and biocompatibility characteristics of rosin, a natural film-forming polymer. Both in vitro as well as in vivo methods were used for assessment of the same. The in vitro degradation of rosin films was followed in pH 7.4 phosphate buffered saline at 37°C and in vivo by subdermal implantation in rats for up to 90 days. Initial biocompatibility was followed on postoperative days 7, 14, 21, and 28 by histological observations of the surrounding tissues around the implanted films. Poly (DL-lactic-co-glycolic acid) (PLGA) (50:50) was used as reference material for biocompatibility. Rate and extent of degradation were followed in terms of dry film weight loss, molecular weight (MW) decline, and surface morphological changes. Although the rate of in vitro degradation was slow, rosin-free films showed complete degradation between 60 and 90 days following subdermal implantation in rats.
Rai, R.; Collum, D.B. Tetrahedron Lett.
1994, 35, 6221.
Wurster coating provides excellent film uniformity and god active-component distribution. The authors describe the results of a study using the Wurster method with positron emission particle tracking technology.
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Amylose-ethylcellulose film coatings obtained from organic-based solvents were investigated as potential vehicles for colonic drug delivery. Amylose, in the form of an amylose-butan-1-ol dispersion, and ethylcellulose, dissolved in either ethyl lactate, ethanol, or propanol and plasticized with dibutyl sebacate, were mixed in various proportions and applied using a fluidized bed coater to achieve a range of film thicknesses on 5-aminosalicylic acid pellets. Drug release from the coated pellets was assessed under gastric and small intestinal conditions in the presence and absence of pepsin and pancreatin using dissolution methodology, and also within a simulated colonic environment involving fermentation testing with human feces in the form of a slurry. Under upper gastrointestinal tract conditions, the rate and extent of drug release were found to be related to the thickness of the coating and the ratio of amylose to ethylcellulose within the film.
The formulation of drugs into soft gelatin capsules has gained popularity throughout the past decade due to the many advantages of this dosage form. The bioavailability of hydrophobic drugs can be significantly increased when formulated into soft gelatin capsules.1,2 Many problems associated with tableting, including poor compaction and lack of content or weight uniformity, can be eliminated when a drug is incorporated into this dosage form.3 Improved stability of drugs that are highly susceptible to oxidation can be achieved when formulated into a soft gelatin capsule.
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The goal of this study was to determine which combination of excipients would result in a tablet core that would be suitable for use in an aqueous enteric film-coating process. A relatively simple formulation of microcrystalline cellulose (MCC) and partially pregelatinized starch (P-PGS) was found to provide the necessary properties.MCC in the formulation provides the compactability needed to produce a tablet that will withstand the mechanical stresses of the film-coating process. P-PGS provides the dissolution characteristics and is responsible for the stability characteristics in this moisture-sensitive, enteric film-coated application. It was also found that P-PGS could be used to reduce the deleterious effects of superdisintegrants in formulations.
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The authors describe a tablet press concept for the facile production of compression coated tablets by obviating the need to manufacture core tablets in a separate operation. Prototypes of the dosage form were produced with special tooling on a laboratory press and evaluated for their ability to form compression-coated tablets from poorly compactible substances and to control the release of drugs within the core by using suitable polymers in the coating blend..
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Latex dispersions have proved to be very useful in aqueous-based film coating, especially in controlled-release applications. Film coatings commonly are colored with pigments to provide a means of product identification and to enable the manufacturer to distinguish similar products. Colored films allow the manufacturer to impart a distinct appearance to the dosage form, which is useful from a marketing standpoint. The use of pigments in film coatings also facilitates patient recognition and makes the product aesthetically appealing. Because both the latex polymer and pigment particles exist in the colloidal or near-colloidal state, interactions caused by surface properties may sometimes lead to unstable formulations. This article examines some of the issues that are important to consider when formulating latex dispersions with pigments.
new chemical entity often is first formulated as a free-flowing granulation for encapsulation within hard gelatin capsules. During the course of clinical development, the drugcontaining granulation usually is modified for compaction into a tablet product. The tablet product subsequently may be film coated for taste masking, identification, or other purposes. Tablets are the most preferred and widely used dosage form because of their ease of administration, lower cost of manufacture, and elegance. In this article, we describe a means of producing tablet dosage forms (specifically, compression-coated tablets) from granulations or blends that do not readily form a compact. The compression-coating granulation or blend can be preformulated to provide desired functionalities to the coating.
C ellulose acetate (CA) is a polymeric excipient commonly used in formulating pharmaceutical dosage forms. CA can be used in direct compression or powder granulation for making tablets (1). It is well known that CA is used for forming the semipermeable membrane in an osmotic delivery system (2–4).
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