For many multi-particulate applications, the required particle size to achieve the proper drug load or to avoid poor mouth-feel has become very small, oftentimes in the 50-300 micron range. When these particles need to be taste masked, the amount of coating required can exceed 400% weight gain to properly taste mask the particles. Those high coating weight gains can lead to several processing problems, including extremely long processing times, agglomeration issues and large amounts of organic solvents. This study focused on an alternative method for taste masking small particles, utilizing a dry polymer coating technique.
Dry powder layering of Active Pharmaceutical Ingredients (API) offers several advantages when the amount of drug loading is high, including fast processing times, high yield, high content uniformity and low agglomeration. The process is not often used in low-dose API loading, due to concern that content uniformity may be compromised in processes that may last under 10 minutes. This study focused on whether acceptable content uniformity could be achieved via dry powder layering at low coating levels.
Ethylcellulose is a commonly used polymer in barrier membrane coating, applied organically or aqueously to develop extended release (ER) multiparticulate (MP) dosage forms. Recently, a novel grade of ethylcellulose, ETHOCEL™HP, was developed that can be applied as a dry powder coating. This technology results in the elimination of large quantities of solvent or water during the application process and achieves a significant reduction in coating process times.1 For dry powder coating, the plasticizer plays a key role in adhering, softening and coalescing the ethylcellulose particles to develop a consistent barrier membrane.1,2 In this investigation, metoprolol tartrate (MT) multiparticulates were used for dry powder layering with ETHOCEL HP, using oleic acid and dibutyl sebacate (OA:DBS) as a plasticizer, and the influence of the plasticizer combinations on ethylcellulose glass transition temperature (Tg) ) was evaluated.3 In addition, the long term stability of the ER coated multiparticulates was studied.
Bottom Spray Wurster technology is commonly used in the pharmaceutical industry as a method for applying active and functional coatings, including enteric coatings, to multiparticulate substrates. Typically dilute solutions or suspensions of polymer mixed with appropriate glidant to reduce blocking during the drying of the polymer coat is applied via air atomizing spray guns. Having to dilute the solution can increase the application time needed for enteric protection.
Many API’s and excipients are heat sensitive. This can prove problematic when using regular film coating systems based on HPMC or PVA because high temperatures are required in order to efficiently apply a uniform coating. If the elevated temperatures are not used, a variety of issues related to over-wetting may occur. The objective of this study was to evaluate the performance of a modified pea starch polymer based coating formulation processed at a tablet bed temperature lower than 25 C.
Ethylcellulose is commonly used throughout the pharmaceutical industry for barrier membrane coatings for sustained drug release. In many formulations that utilize ethylcellulose coatings, soluble pore formers are used to modify and speed up the release of API from the coated material. Hydroxypropyl Methylcellulose (HPMC) is a common pore former in these formulations that is easily blended into traditional solution preparations of ethylcellulose and applied at precise ratios to produce predictable, repeatable drug release. The recent development of a novel ethylcellulose grade for use in dry powder coatings of multiparticulates has offered the pharmaceutical industry a vastly improved method for applying barrier membrane coatings in a safe, fast and efficient process.
Controlled release coatings of ethylcellulose were applied to drug loaded sugar spheres with three different processes: dry powder layering, aqueous Wurster coating and organic solvent based Wurster coating. Comparative analysis of the three processes showed that the dry powder layering process was able to apply the ethylcellulose coatings in a faster, more efficient process than the traditional spray coating systems and still achieve controlled release.
Bottom Spray Wurster technology is commonly used in the pharmaceutical industry as a method for applying active and functional coatings to various multi-particulate substrates. For medium to high drug load applications this technology often becomes complicated when processes require large volumes of dilute solutions or poorly soluble API’s require organic solvents. Large suspension volumes force long duration spray times, can be subject to sedimentation with solution line and spray gun problems leading to agglomeration of substrate particles.
ETHOCEL HP is a micronized ethylcellulose dry powder specifically designed to achieve controlled release barrier membranes using a rotor system. This dry powder coating shows 40 – 60% reduction in coating times versus spray coating alternatives such as aqueous ethylcellulose dispersions or solvent based spray coatings and is solvent free. The coating process feeds ETHOCEL HP from the dry powder state along with a combination of water and plasticizer to allow proper particle-particle and particle-substrate adhesion and drives down the Tg of ethylcellulose to temperature relevant to film formation. Due to the nature of this coating process, curing is a required process parameter for improved film formation and stability. This study highlights the influence of static and dynamic curing steps on dissolution performance and stability at accelerated conditions.
Conventional functional coating systems require the use of aqueous coating dispersion with limitation for highly moisture sensitive actives or solvent systems requiring additional safety measures. As there is no drying for the solvent needed, powder layering processes are quicker and it do not require the use of any solvents and uses only minimal amount of water emulsified with liquid plasticizer as a binder to facilitate film formation.
Currently, when coating tablets with moisture sensitive actives, aqueous film coatings based on PEG, PVA, and HPMC are recommended to be applied at high product temperatures to overcome the API’s sensitivity. Unfortunately, this approach can lead to heat degradation of the API and other potential physical tablet coating defects.
API layering onto multi-particulate core materials has become an increasingly popular method of drug delivery in the pharmaceutical industry in recent years. The ability to control dosing, customize the dosing rate and reduce the risk of dose dumping along with the ability to create orally disintegrating tablets (ODT’s) with controlled release particles are all advantages to multi-particulate dosage forms.
A starch microsphere was used as a core material in a dry powder layering process where an 80% Active Pharmaceutical Ingredient (API) content was required in a particle with a finished size below 250 microns. Size, shape, efficiency, process and content analysis of the finished coated particles showed that the starch microspheres were successfully used as a core material to create high API loaded particles under 250 microns in size.
Spray coatings of ethylcellulose for controlled release on multi-particulate dosage forms are common in the pharmaceutical industry, but can be disadvantageous because of long process times, need for organic solvent capabilities, and particulate agglomeration. This study highlights the advantages of a rotor dry powder layering process in overcoming these deficiencies by comparing performance, productivity and cost to solvent based Wurster coating and aqueous-based Wurster coating.
Taste masking of multi-particulate dosage forms has become widespread in the pharmaceutical industry, particularly with small particles used in ODT applications. The amount of coating required to fully mask the API can be variable as the size and shape of the substrate changes. This study attempts to quantify the effect of size and shape on the coating
requirements to fully taste mask multi-particulates.
Wurster coating of multi-particulates with polymer suspensions and solutions is widespread in the pharmaceutical industry. Several formulations for polymer coatings of aqueous dispersions and organic solvent based polymer systems require glidants such as talc to be suspended into the polymer solutions to cut down on polymer tackiness and reduce agglomeration. These glidants can fall out of solution during the process, causing gun plugging, line plugging, extended processing times and inefficient coating. This study focuses on a modification to an existing Wurster spray system to add solid glidants via a powder feeder in dry form during the Wurster coating process.
To investigate the process of dry powder drug layering and enteric coating on three spherical core materials: two traditional cores, sugar/starch and microcrystalline cellulose, and a newer type of core manufactured from starch and maltodextrin. To compare dissolution and content uniformity for the Active Pharmaceutical Ingredient (API) applied at different percentages on powder layered cores and enteric coated finished spheres.