Article

Novel low-molecular-weight hypromellose polymeric films for aqueous film coating applications

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Abstract

The concentration of hypromellose (HPMC) is known to significantly impact the viscosity of coating solutions. The purpose of this study was to determine the viscosity of novel low-molecular-weight (LMW) HPMC products as a function of polymer concentration. The mechanical properties and water vapor permeability of free films prepared from these novel LMW HPMC polymers were also determined and the results were compared with films prepared with conventional HPMC. Solutions of LMW and conventional HPMC 2910 and 2906 containing up to 40% polyethylene glycol (PEG) 400 were prepared and the viscosities were measured using a Brookfield viscometer. Solutions were then cast onto glass plates and stored at 30?C and 50% relative humidity until films were formed. A Chatillon digital force gauge attached to a motorized test stand was used to quantify the mechanical properties of the films, whereas water vapor permeabilities were determined according to the ASTM E96 M-05 water method. As expected, the novel LMW polymer solutions exhibited significantly lower viscosities than the conventional comparators at equivalent polymer concentrations. Film strength of the LMW materials was lower than films prepared from the conventional HPMC solutions, although this effect was not as evident for the HPMC 2906 chemistry. Increasing concentrations of the plasticizer resulted in decreased tensile strength and Young?s modulus and increased elongation as well as increased water vapor permeability, irrespective of polymer type. No statistical difference was found between the tensile strength to Young?s modulus ratios of the F chemistry LMW and conventional HPMC polymer films.

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Preprint
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Article
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Abstract The effects of plasticizer, polyethylene glycol (PEG-600), on the sucrose permeability, void volume and morphology of cellulose acetate free films were investigated. The sucrose permeability of cellulose acetate free films was found to decrease with increasing PEG-600 to a minimum and increase dramatically when they were plasticized by over 30% (w/w) PEG-600. The decrease in sucrose permeability of cellulose acetate free films with increasing plasticizer at low plasticizer concentrations could be interpreted by the antiplasticization effect, and the dramatic increase of sucrose permeability of cellulose acetate free films at high plasticizer level could be explained by the formation of plasticizer channels. The void volume of cellulose acetate free films were calculated by determining the water content in the films, and the effect of PEG-600 on the morphology of cellulose acetate free films was studied by using the scanning electron microscopy (SEM). Both the void volume and SEM studies supported the assumption that the plasticizer channels would be formed in the polymer films which contain high concentration of plasticizer.
Article
The influence of plasticizers in film coating formulations on the adhesive properties of an acrylic resin copolymer was determined using the butt adhesion technique. Hydrophilic and hydrophobic plasticizing agents were incorporated into aqueous dispersions of Eudragit® L 30 D-55 and coated onto hydrophilic and hydrophobic tablet compacts. Using data obtained from a Chatillon digital force gauge attached to a motorized test stand, force-deflection profiles, similar to stress-strain curves generated in the tensile testing of free films, were constructed and the force of adhesion, elongation at adhesive failure, and adhesive toughness were determined. Plasticizer concentration and plasticizer type were found to influence the adhesive properties of the acrylic polymer. An increase in adhesive toughness was found when the concentration of triethyl citrate (TEC) in the coating formulation was increased from 20 to 30%, which was attributed to an increase in the elasticity of the film and a decrease in the internal stresses within the polymer. Films containing water soluble plasticizers were found to adhere more strongly to the tablet compacts than the water insoluble agents, due to more effective disruption of the intermolecular attractions between the polymer chains. Adhesion of the polymer to tablet compacts was found to be significantly influenced by the hydrophobicity of the tablet surface when the water soluble plasticizers were incorporated into the film coating, whereas no significant differences in the adhesive properties were found when the polymer was plasticized with water insoluble agents. Aging of the film-coated tablets resulted in a decrease in adhesive toughness, irrespective of the environmental storage condition.
Article
Data have been produced on the parameters which influence the development of internal stresses within aqueous HPMC film coats plasticized with glycerol in an attempt to calculate the magnitude of internal stress generation. Films have been prepared under conditions which equate to those experienced during film coating processes. The changes in mechanical and thermal properties of fresh films formed at different tablet bed conditions have been studied during their ambient storage. The contribution of internal stresses from three sources are calculated individually and a single equation is used to estimate the total internal stress within a film. This equation considers the contribution made by the volumetric changes of the tablet core during ambient conditions in addition to those caused by other well-established mechanisms. The results of these calculations showed that the total internal stress is influenced, not only by these volumetric changes, but also by the conditions in which the film coating process was performed. The possibility of the film coating undergoing failure is also discussed.
Article
The enteric coating of soft gelatin capsules (SGC) containing ibuprofen in either PEG 400 or Miglyol© was investigated. The effects of two plasticizers, triethyl citrate (TEC) and tributyl citrate (TBC), on the physical and enteric properties of SGC coated with Eudragit ® L 30 D-55 were studied. The water soluble plasticizer TEC was found to be a good plasticizing agent for the Eudragit® L 30 D-55 irrespective of the fill liquid, while the TBC provided satisfactory results only for capsules containing the hydrophobic fill liquid, Miglyol ®. The combination of TEC and TBC provided effective plasticization for the acrylic coating regardless of the fill liquid. A subcoat of HPMC showed no effect on the enteric protection of either Miglyol® - and PEG-containing capsules that were stored at room temperature and zero percent relative humidity. The moisture content of the gelatin shell of the film coated SGC stored at room temperature and at 0 or 96% relative humidity was followed as a function of time. The load strength of the capsules was measured during 3 months of storage using an Instron universal testing apparatus, and the physical-mechanical properties of the capsules were correlated with the moisture content of the SGC. As the moisture content of the gelatin decreased, all formulations exhibited an increase in load strength.
Article
The use and potential of solubility parameters for pharmaceutical dosage form design are reviewed in this paper. Specific reference is given to the development of the approach, its previous usage and likely future applications. The advantages, assumptions and limitations of this type of approach are also described.
Article
To investigate the physical stability and drug release-related properties of the aqueous polymer dispersions Kollicoat((R)) SR 30 D and Aquacoat((R)) ECD (an ethylcellulose-based dispersion) in the presence water-soluble polymers (pore formers) with special attention to the potential flocculation of the polymer dispersions. A precise characterization of the flocculation phenomena in undiluted samples was monitored with turbidimetric measurements using the Turbiscan Lab-Expert. Theophylline or propranolol HCl drug-layered pellets were coated with Kollicoat((R)) SR 30 D and Aquacoat((R)) ECD by the addition of water-soluble polymers polyvinyl pyrrolidone (Kollidon((R)) 30 and 90 F), polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat((R)) IR), and hydroxypropyl methylcellulose (Pharmacoat((R)) 603 or 606) in a fluidized bed coater Glatt GPCG-1 and drug release was performed according to UPS paddle method. Stable dispersions were obtained with both Kollicoat((R)) SR 30 D (a polyvinyl acetate-based dispersion) and Aquacoat((R)) ECD with up to 50% hydrophilic pore formers polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat((R)) IR) and polyvinyl pyrrolidone (Kollidon((R)) 30). In general, Kollicoat((R)) SR 30 D was more stable against flocculation than Aquacoat((R)) ECD. Stable dispersions were also obtained with higher amounts of water-soluble polymer or by reducing the concentration of the polymer dispersion. Flocculated dispersions resulted in porous films and, thus, in a sharp increase in drug release. Kollicoat((R)) SR 30 D was more resistant to flocculation upon addition of water-soluble polymers than Aquacoat((R)) ECD. The continuous adjustment of drug release from Kollicoat((R)) SR 30-coated pellets was possible with Kollicoat((R)) IR amounts over a broad range.
Article
Polymeric film coatings have been applied to pharmaceutical solids for decorative, protective, or functional purposes. The application process is quite complex, with variables related to the coating formulation, substrate properties, processing parameters, and interactions thereof, all of which can affect product performance. This article describes a number of experimental techniques used to determine the physical, mechanical, adhesive, thermal, and permeability properties of free and applied films. These analytical tools can be used to optimize product performance, advance our knowledge of the film formation process, and investigate interactions between the coating and the solid surface. Through a better understanding of film-coating processes, the cause of problems that arise during manufacturing, defects observed in the coating, and changes in performance upon subsequent storage may be more quickly and accurately resolved.
Article
Continuous film coating processes are recognized for their high production rates but have had slow acceptance for pharmaceutical production because of perceived high product losses during start-up and shut-down. In this article, the recent improvements in continuous coater designs were evaluated with respect to coating uniformity and reduction in product losses. Two separate studies represent trials conducted in newly redesigned continuous coating pans from two different coating pan manufacturers. Multivitamin tablets were coated with Opadry((R)) II, high performance film coating system, in both batch and continuous modes in the continuous coater. Tablet samples collected throughout all phases of the process were tested for color development and uniformity. Soft gelatin capsules were coated with a delayed release coating formulation, Nutrateric((R)), nutritional enteric coating system. Samples of the soft gelatin capsules were taken throughout the process and tested for resistance to simulated gastric fluid as a measure of coating uniformity and delayed release functionality performance. The results from both the immediate release and delayed release case studies support the assertion that continuous coating processes are capable of applying aqueous film coatings with significant improvements in coating uniformity and reduction in product loss.
Article
Food effects might substantially alter drug release from oral controlled release dosage forms in vivo. The robustness of a novel type of controlled release film coating was investigated using various types of release media and two types of release apparatii. Importantly, none of the investigated conditions had a noteworthy impact on the release of freely water-soluble diltiazem HCl or slightly water-soluble theophylline from pellets coated with ethylcellulose containing small amounts of PVA-PEG graft copolymer. In particular, the presence of significant amounts of fats, carbohydrates, surfactants, bile salts, and calcium ions in the release medium did not alter drug release. Furthermore, changes in the pH and differences in the mechanical stress the dosage forms were exposed to did not affect drug release from the pellets. The investigated film coatings allowing for oral controlled drug delivery are highly robust in vitro and likely to be poorly sensitive to classical food effects in vivo.
Article
The mechanical strength of film-coated tablets has been assessed using the diametral compression test. The results show that the influence of the film is more complex than that suggested by Stern (1976). The film may increase the breaking load of the core itself by acting as a padding material during the test and also by filling in surface irregularities. The film may also have enough intrinsic strength and elasticity to hold the core together once it has broken. The maximum breaking load to completely fracture the coated tablet is related to film properties, but the relation is not a simple one.
Article
Poly(vinyl alcohol) has not previously been examined in much detail as a controlled release polymer for use in pharmaceutical formulations. However, this food grade polymer has barrier and tensile properties which make it attractive for such applications. The effects of several diluents and fillers on Poly(vinyl alcohol) (PVAL) coatings have been determined using both mechanical property and water vapor permeability measurements. It has been found that the alcohol ethoxylate Neodol 23-6.5 (CH3(CH2)11-O-(CH2-CH2-O)6-H) acts as a plasticizer for PVAL only up to 15-20 wt% in contrast to 600 molecular weight Polyethylene Glycol (PEG 600), which continuously plasticizes PVAL. The effects of Neodol on PVAL mechanical properties and water vapor permeability at higher concentrations can be explained in terms of Neodol phase separation and has been confirmed with DSC. The inert filler and whitener titanium dioxide (TiO2) monotonically degrades film mechanical properties and increases water vapor permeability of the coating. Attempts to correlate coating dust generated during particle attrition tests with mechanical property measurements were unsuccessful. A correlation between accelerated granule stability and water vapor permeability of the PVAL coating was established.
Article
The effect of different grades of hydroxyethyl cellulose (HEC) and hydroxypropyl methllcellulose (HPMC) on the film-formation and taste-masking ability for ibuprofen granules was evaluated. Three batches of coated ibuprofen granules were prepared using a roto-granulator, each with a different coating composition. Two grades of HEC [MW300,000 (H) and MW90,000 (L)] were combined with three different grades of HPMC [MW 11,000 (L), MW 25,000 (M) and MW 35,000 (H)] to prepare the coating solutions. Mechanical strength and physical properties of the polymer films were evaluated. Films made from HPMC (L)/HEC (H), HPMC (M)/HEC (H), and HPMC (H)/HEC (H) were stronger and more flexible than the HPMC (L) HEC (L) films. The assay, dissolution, particle size distribution, and environmental scanning electron microscopy (ESEM) data of the three batches of the coated ibuprofen granules were similar.
Article
The major aim of the present work was to study the effects of various formulation and processing parameters on the resulting drug release kinetics from theophylline matrix pellets coated with aqueous hydroxypropyl methylcellulose acetate succinate (HPMCAS) dispersions. The plasticizer content, coating level and curing conditions significantly affected the release patterns in 0.1 M HCl, whereas no major effects were observed in phosphate buffer, pH 7.4. Due to the significant size of the HPMCAS particles (being in the micrometer range), their coalescence was particularly crucial and not complete upon coating. Consequently, at low coating levels continuous water-filled channels connected the bead cores with the release medium through which the drug could rapidly diffuse, resulting in high release rates even at low pH. In contrast, at high coating levels such continuous connections did not exist (due to the increased number of polymer particle layers), and drug release was controlled by diffusion through the macromolecular network resulting in much lower release rates in 0.1 M HCl. Importantly, pellet curing at elevated temperature and ambient relative humidity or exposure to elevated relative humidity at room temperature did not significantly alter the microstructure of the coatings, leading to only slightly decreased drug release rates. In contrast, pellet curing at elevated temperature combined with elevated relative humidity induced significant further polymer particle coalescence, resulting in a change of the underlying drug release mechanism and significantly reduced drug release rates.
Article
The effect of triethyl citrate (TEC) and different molecular weights and concentrations of polyethylene glycol (PEG), in addition to the effect of different water-soluble polymers and dispersions at different levels, hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), carbomer 940, polyvinyl alcohol (PVA), ethyl cellulose (EC), on the mechanical and thermal properties, drug permeability, and porosity of free shellac films were investigated. Shellac films were cast from aqueous solutions, and their mechanical properties were studied by tensile test. Thermal analyses were performed using differential scanning calorimetry (DSC). The results showed that the addition of plasticizer caused a decrease in both elastic modulus and glass transition temperature (T(g)) and an increase in elongation at break of free shellac films. This effect was related to the concentrations of plasticizers. Different molecular weights of PEGs have different plasticization mechanisms.Moreover, the incorporation of different amounts of HPMC, MC, or carbomer in free shellac films caused an increase in the flexibility, decrease in T(g), and a marked increase in drug permeability of free shellac films, whereas the addition of PVA caused a decrease in flexibility and drug permeability and an increase in T(g). Addition of EC resulted in a slight decrease of the elasticity and a small decrease in drug permeability. However it does not show a considerable effect on the T(g). In addition, it was found that the drug permeability is directly related to the mechanical properties and T(g) of shellac films.
Article
The use of polymer blends as coating materials for controlled drug delivery systems can offer major advantages, including: (i) facilitated adjustment of desired drug release patterns, mechanical properties and drug release mechanisms, (ii) improved film formation and storage stability, and (iii) the possibility to develop novel strategies for site specific drug delivery within the gastro intestinal tract (e.g., colon targeting). However, these systems are more complex than coatings based on only one polymer and care has to be taken when using this type of formulations. For instance, the blended polymers can be incompatible, aqueous polymer dispersions might flocculate and plasticizers potentially redistribute from one polymer into the other during curing and/or long term storage. This article gives an overview on the current state of the art of the use of polymer blends as coating materials for controlled drug delivery, explaining the major advantages and potential pitfalls. Special emphasis is laid on the underlying drug release mechanisms and practical examples for various types of applications are given. Due to the higher complexity of the systems, a thorough understanding of the most important mass transport phenomena involved in the control of drug release can be very helpful to render the optimization of this type of advanced delivery systems more efficient.
Article
Polymeric film coatings have been applied to solid substrates for decorative, protective, and functional purposes. Irrespective of the reasons for coating, certain properties of the polymer films may be determined as a method to evaluate coating formulations, substrate variables, and processing conditions. This article describes experimental techniques to assess various properties of both free and applied films, including water vapor and oxygen permeability, as well as thermal, mechanical, and adhesive characteristics. Methods to investigate interfacial interactions are also presented.
Article
The aim of this study was to evaluate the moisture-protective ability of different polymeric coatings. Free films and film-coated tablets (with cores containing freeze-dried garlic powder) were prepared using aqueous solutions/dispersions of hydroxypropyl methylcellulose (HPMC), Opadry AMB [a poly(vinylalcohol)-based formulation] and Eudragit E PO [a poly(methacrylate-methylmethacrylate)]. The water content of the systems upon open storage at 75% relative humidity (RH) and 22 degrees C (room temperature) was followed gravimetrically. Furthermore, polymer powders, free films and coated tablets were analyzed by differential scanning calorimetry (DSC) and dynamic vapor sorption (DVS). The type of polymer strongly affected the resulting water uptake kinetics of the free films and coated tablets. DSC analysis revealed whether or not significant physical changes occurred in the coatings during storage, and whether the water vapor permeability was water concentration dependent. Using DVS analysis the critical glass transition RH of Opadry AMB powder and Opadry AMB-coated tablets at 25 degrees C could be determined: 44.0% and 72.9% RH. Storage below these threshold values significantly reduces water penetration. Thus, DVS and DSC measurements can provide valuable information on the nature of polymers used for moisture protection.
The role of high-solids coating systems in reducing process costs
  • S Porter
Porter S. (2010). The role of high-solids coating systems in reducing process costs. Tablets Capsules, 8:10–16.
Investigation of a novel hypromellose polymer for high-productivity tablet coating applications
  • T Rogers
  • P Sheskey
  • H Furukawa
  • C Mallon
  • M Trampe
  • D Holbrook
Rogers T, Sheskey P, Furukawa H, Mallon C, Trampe M, Holbrook D. (2008). Investigation of a novel hypromellose polymer for high-productivity tablet coating applications. AAPS Annual Meeting, Atlanta, GA.
Reducing coated tablet defects from laboratory through production scale: performance of hypromellose or polyvinyl alcohol-based aqueous film coating systems
  • C Cunningham
Cunningham C. (2007). Reducing coated tablet defects from laboratory through production scale: performance of hypromellose or polyvinyl alcohol-based aqueous film coating systems. AAPS Annual Meeting, San Diego, CA.
The mechanical properties of hydroxypropylmethylcellulose films derived from aqueous systems part I: the influence of plasticizers
  • M Aulton
  • M Abdul-Razzak