Meetings & Events

1998 MRS Fall Meeting & Exhibit

November 30 - December 4, 1998 | Boston
Meeting Chairs:
 Clyde L. Briant, Eric H. Chason, Howard E. Katz, Yuh Shiohara

Symposium GG—Polymeric Materials - Drugs, Delivery and Devicesymposium GG—Polymeric Materials - Drugs, Delivery and Devices

-MRS-

Chairs

Achim Goepferich, Univ Regensburg 
Thomas Neenan, GelTex Pharmaceuticals Inc
Kathryn Uhrich, Rutgers Univ

Symposium Support 

  • GelTex Pharmaceuticals, Inc.
  • New Jersey Center for Biomaterials & Medical Devices 
Proceedings published as Volume 550 
of the Materials Research Society 
Symposium Proceedings Series.

* Invited paper

SESSION GG1: POLYMER DRUGS AND HYDROGELS 
Chair: Kathryn E. Uhrich 
Monday Morning, November 30, 1998 
Essex East (W)
9:00 AM *GG1.1 THREE GENERATIONS OF BILE ACID SEQUESTRANTS. W. Harry Mandeville , William Braunlin, Karen Miller, James Ward, Pradeep Dhal, Steven Polomoscanik, Chad Huval, Eugene Zhorov, Amy Guo, John S. Petersen, David Rosenbaum, Robert Sacchiero, Cynthia Crosby, Mary Pitruzzello, Dennis I. Goldberg and S. Randall Holmes-Farley, GelTex Pharmaceuticals, Inc., Waltham, MA. Cholestyramine, the first bile acid sequestrant to be marketed, has been in use for over 20 years. Despite its low efficacy, requiring 16-24 g of polymer to achieve 20% LDL cholesterol reduction in hypercholesterolemic individuals, only one other sequestrant, colestipol, has come to market in the ensuing period. GelTex Pharmaceuticals has been involved for over six years in the discovery and development of new, more efficacious polymeric sequestrants. Two binding mechanisms are presented - one that operates via an aggregate binding structure and one that is effective via a defined site binding structure. These two binding mechanisms are compared and contrasted through bile acid binding isotherms and in vivo performance in animal and human models of hypercholesterolemia and fecal bile acid quantitation. The best of these new sequestrants bind bile acids through a combination of hydrophobicity and ion exchange. Optimization and balancing of each of these interactions led us to more efficacious materials. The first of these, colesevelam hydrochloride or CholestaGelÆ, is expected to be three to four times more efficacious than cholestyramine. A third generation product is still in research at GelTex. With another threefold increase in efficacy possible, single tablet therapy may become a reality. 

9:30 AM GG1.2 
AN APPROACH TO CLASSIFY DEGRADABLE POLYMERS. Friederike von Burkersroda, Achim Goepferich , Regensburg Univ, Dept of Pharmaceutical Technology, Regensburg, GERMANY. 

The erosion of a biodegradable polymer is an important parameter for its successful application in drug delivery. The erosion mechanism is, thereby, a significant process to be understood. Despite the successful development of many synthetic polymer materials during the last 3 decades, little progress was made towards a better understanding of polymer erosion. This has hindered many groups working in the field to take full advantage of the potential that biodegradable polymers may have. The objective of our work is to elucidate the degradation mechanisms responsible for bulk eroding polymers, and to gain insight into the basic characteristics of erosion that several classes of synthetic water-insoluble degradable polymers share. Poly(D,L-lactic acid) (PLA), poly(D,L-lactic -co- glycolic acid) and diblock copolymers of PLA and poly(ethyleneglycol) served as model compounds. When eroding these polymers in vitro (0.1M PBS pH 7.4, 37C) we obtained sigmoid erosion profiles that are characteristic of bulk erosion. Erosion starts after a lag period lasting between days to weeks. From the investigation of eroded polymer matrices by GPC and NMR we conclude that autocatalytically accelerated degradation inside the matrices cannot be the only mechanism contributing to the observed erosion behavior. The release profiles of the degradation products such as lactic and glycolic acid or PEG support these findings. From our results we hypothesize that the erosion of these polymers may be controlled, in addition to other processes, by percolation phenomena. These findings allowed us to optimize drug delivery devices and may lead to the development of an erosion theory that that does not limit polymers to surface eroding and bulk eroding classifications but also covers the continuum between these two extremes. 

9:45 AM GG1.3 
SUPERCRITICAL FLUID TECHNOLOGY IN POLYMER PROCESSING AND DRUG DELIVERY DEVICE MANUFACTURING. Steve M. Howdle, Kevin M. Shakesheff , Martyn C. Davies, Schools of Chemistry and Pharmaceutical Sciences, The University of Nottingham, UK; Frederick S. Mandel, J. Don Wang, Ferro Corporation, Technical Center, OH. 

Supercritical carbon dioxide (scCO2) is an exceptionally versatile and clean solvent. We will show the potential for use of a proprietary scCO2 mixing technology to manufacture drug delivery devices leading to materials incorporating high loadings of fragile drug molecules. Moreover, this technology provides excellent control of polymer morphology; from highly porous microparticles to monolithic formulations of biodegradable polymers. By understanding the nature of the interaction between polymer and scCO2, and by mainitaining exceptional temperature and pressure control, it is possible to control the pore size and surface area of devices incorporating over 60% of drug homogeneously distributed throughout the polymer. This technology is applicable to a very wide range of drugs including of protein-based drugs, and drug delivery device types. 

10:30 AM *GG1.4 
THE USE OF STIMULI RESPONSIVE LIPOSOMES FOR IN-SITU FORMATION OF PROTEIN HYDROGELS. Eric Westhaus, Phillip B. Messersmith , Northwestern University, Division of Biological Materials, Chicago, IL. 

Liposomes have been widely investigated as vehicles for in-vivo delivery of therapeutic and diagnostic agents. Typically, liposomes loaded with drugs or other compounds are injected intravenously and are systemically dispersed by the circulatory system, although methods for targeted delivery to a specific tissue or organ have been investigated. We are investigating new ways of utilizing liposomes for the purposes of in-situ formation of biomaterials. In this presentation we will describe the use of thermally triggered release of calcium from liposomes to activate rapid enzyme-catalyzed crosslinking of proteins to form hydrogels. Enzyme assays were used to demonstrate that stimuli triggered release of calcium from liposomes can be used to activate calcium-dependent transglutaminase (TG) enzymes. The activated TG enzyme, in turn, catalyzes the crosslinking of glutamine and lysine containing substrates, such as proteins and polypeptides. This thermally triggered approach was used to develop a proteinaceous fluid that solidified into a hydrogel within minutes when warmed from room temperature to body temperature. These in-situ gelling materials may be useful for wound healing and local drug delivery applications. 

11:00 AM GG1.5 
ARTIFICIAL PROTEIN HYDROGEL MATERIALS. James L. Harden , Department of Chemical Engineering, Johns Hopkins University, Baltimore, MD; Wendy A. Petka, 3M, Minneapolis, MN; Jill Sakata, Department of Polymer Science and Engineering, University of Massachusetts, Amherst, MA; David A. Tirrell, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA. 

Recombinant DNA methods were used to create a new class of artificial proteins that undergo reversible gelation in response to changes in pH or temperature. These proteins consist of terminal alpha-helical ``leucine zipper'' domains flanking a central, water-soluble polyelectrolyte segment. The formation of coiled-coil aggregates of the terminal domains in near-neutral pH solution triggers formation of a polymer hydrogel, with the central polyelectrolyte segment retaining solvent and preventing precipitation of the chains. Dissociation of the coiled-coil aggregates through elevation of pH or temperature causes dissolution of the gel and a return to the viscous behavior characteristic of a polymer solution. The pH and temperature range of the hydrogel state and its viscoelastic properties may be systematically varied through precise changes of the length, composition and charge density of the terminal and central blocks. Such control is of value in designing hydrogels with predetermined physical properties and makes these biosynthetic triblock copolymer systems attractive candidates for use in molecular and cellular encapsulation and in controlled reagent delivery. 

11:15 AM GG1.6 
SYNTHESIS AND SWELLING BEHAVIOR OF HYDROGELS BASED ON GRAFTED CHITOSAN. Mehrdad Yazdani-Pedram , Univ Chile, Dept of Organic Chem, Fac Chem and Pharm Sci, Santiago, CHILE; Jaime Retuert, Univ Chile, Dept of Chem, Fac Phys and Math Sci, Santiago, CHILE. 

Grafting reactions of vinyl monomers onto polysaccharides is a useful method to modify their properties. In this work hydrogel forming polymers were grafted onto chitosan,(poly-(1-4)-2- amino -2-deoxy - D-glucose) (CHI), in a homogeneous phase by using potassium persulfate and ferrous ammonium sulfate as redox initiator. A commercial sample of CHI, characterized in our laboratory having degree of acetylation of 19.4% and viscosity average Molecular Weight of 385000 was used. Grafting of Polyacrylic acid resulted in obtaining insoluble products without the necessity of using a crosslinking agent. Depending on the particular set of reaction conditions, grafting percentages (%G) between 220% and 1600% were obtained. On the other hand, in the case of CHI grafted with Acrylamide, soluble products were obtained where N,N-methylene bisacrylamide was used as crosslinking agent. The %G obtained for this monomer are much lower (<300%) than the case of acrylic acid. The increase in the initial mass of CHI after grafting and separation of the homopolymer, together with the presence of new absorption bands in the FTIR spectra of modified CHI were taken als proof of grafting. It was found that the solubility and the swelling capacity of CHI were significantly changed by chemical modification performed. 
Acknowledgments: Financial support from CONICYT ( Project Fondecyt 1981045) is gratefully acknowledged. 

11:30 AM GG1.7 
PHASE RELATIONS AND SWELLING BEHAVIOR IN POLY(VINYL METHYL ETHER)HYDROGELS. Robrecht Moerkerke, Frank Meeussen, Ronald Koningsveld, Hugo Berghmans , University of Leuven, BELGIUM; Wim Mondelaers, Etienne Schacht, University of Ghent, BELGIUM; Karel Dusek, Institute of Macromolecular Chemistry, Prague, CS; Karel Solc, Central Michigan University, Midland, MI. 

The discontinous swelling behavior of poly(vinyl methyl ether)(PVME) hydrogels around 37C makes them interesting materials for practical applications like controlled drug release, transfer of heat into work etc. Such a behavior results from the interference of a network/network miscibility gap (Lower Critical Solution Temperature) with the swelling curve and can be discussed on the basis of a concentration dependent interaction function. The purpose of this contribution is to get a better theoretical and experimental insight in this phenomenon.
The introduction of this concentration dependence in the description of the solution behavior of the non-cross-linked systems leads to three different types of demixing. One of them (type III) shows two interfering demixing domains and two stable critical points. At the low polymer concentration side, the limiting coordinates of the critical point at infinite polymer molecular mass are a polymer concentration of zero and the -temperature. The position of the critical point in the high concentration range is independent of this molecular mass. 
The extension of this approach to the corresponding swollen networks leads to the conclusion that the type of phase behavior of the corresponding linear system governs the type of swelling behavior. The cross-linked analogues of a linear type III system show discontinuous swelling behavior. 
This type III demixing behavior is observed with the system PVME/water and can be described by the theoretical model. The discontinuous swelling behavior of the cross-linked analogue in water has been verified experimantally through calorimetric observations and the mesurement of the degree of swelling. The interference of the equilibrium swelling curve with the demixing curve leads to an invariant situation. Water is in equilibrium with a demixed network in which equilibrium is established between diluted and concentrated domains. These data confirm the theoretically predicted phase behavior of such networks. 
The occurence of specific interactions between PVME and water is supported by experimental evidence. A stable molecular complex is formed beteen the polymer and water with two molecules of water per chain repeating unit.

SESSION GG2: POLYMERIC DRUGS AND DELIVERY SYSTEMS 
Chair: Achim Goepferich 
Monday Afternoon, November 30, 1998 
Essex East (W)
1:30 PM *GG2.1 
MULTIVALENT AND POLYMERIC DRUGS. George M. Whitesides , Harvard University, Dept of Chemistry, Cambridge, MA. 

Multivalent processes in biology are those that involve the simultaneous interaction of multiple receptors with multiple ligands. It is widely appreciated that multivalent processes are important in many biological systems: the interaction of immunoglobins with the surfaces of bacteria, the adhesion of viruses to the surfaces of cells, and the interaction of lymphocytes with inflamed endothelial tissue are all examples of multivalency. Although the qualitative aspects of multivalency are agreed to, the energetic or physiological advantages that may come with these interactions are not, in general, well defined, and there are surprisingly few quantitative measures of the influence of multivalency on the strength of binding: even the advantage that comes from bivalent interaction of an antibody with a surface presenting antigen-one of the most common processes in immunology-is not a well-defined number. 
One way of agonizing multivalent interactions is with multivalent ligands. This talk will summarize the biophysics of one such system: that is, that based on the interaction of influenza virus with erythrocytes. The polyvalent agonists for this interaction are a series of polyacrylamides presenting sialic acid moieties as side-chains. This system provides a model with which to explore many of the simple manifestations of high-order polyvalency. Many of these phenomena are now understood, with various degrees of precision; translating in vitro assays into biological activity is just beginning. The seminar will also outline studies of simpler multivalent systems for comparison: for example, immunoglobins and lectins with multivalent ligands. The advantage in binding that comes with multivalency in these low-valent systems can also be surprisingly large. Together, these studies provide at least a set of representative data suggesting the range of effects that multivalency can exert on dissociation constants. 

2:00 PM GG2.2 
AN INVESTIGATION OF THE RELEASE PROPERTIES OF A CATIONIC DRUG FROM A HYDROPHOBIC POLYANHYDRIDE MATRIX AS A FUNCTION OF DISSOLUTION MEDIUM. Eric Ginsburg , Dennis Stephens, Dan Robinson, Youqin Tian, Rong Ming Liu, Xiaoyan Gao, Luk Li, Peter Tarcha, H.-C. Chang, Hospital Products Division, Abbott Laboratories, Abbott Park, IL; Timothy Stultz, Univ. of Iowa, College of Pharmacy, Div. of Pharmaceutics, Iowa City, IA; Merrill Nuss, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL. 

A drug delivery device consisting of gentamicin sulfate particles dispersed in a biodegradable polyanhydride matrix is being developed for the treatment of osteomyelitis. The drug/polymer mixture is injection molded to form beads to be implanted during joint replacement surgery. The in vitro release properties of the beads have been examined extensively. The rate of gentamicin release has been found to be slower in pH 7.4 phosphate buffer than in unbuffered water, although the opposite trend is found for the rate of polymer dissolution from a placebo bead. By monitoring the release of gentamicin, monomer and sulfate independently, a model to explain these observations has been developed. 
The experimental results are consistent with an ion-exchange process occurring in the bead immersed in phosphate buffer, in which gentamicin forms a salt with the carboxylate of the monomer and sulfate is released to the dissolution medium. This salt has been found to be poorly soluble. On a macroscopic level, magnetic resonance imaging (MRI) indicates the formation of a hydrophobic shell around the eroding bead. It is hypothesized that this shell is comprised of the gentamicin/monomer-carboxylate salt. In unbuffered water, sulfate and gentamicin release occurs at similar rates, and when beads are placed in water, no shell is observed by MRI. 

2:15 PM GG2.3 
SALICYLIC ACID RELEASE FROM A POLYMERIC PRODRUG. Laura Erdmann , Kathryn Uhrich, Rutgers University, Dept of Chemistry, Piscataway, NJ; Braz Macedo, Center for Dental and Oral Health, UMDNJ-Dental School, Newark, NJ. 

We have synthesized a polymeric prodrug that is noncytotoxic, biocompatible, and hydrolytically degrades into pharmacologically active components. The polymer is a poly(anhydride-ester) composed of alkyl chains linked by ester bonds to aromatic moieties such as salicylic acid. With the medicinal properties of salicylic acid and ease of metabolism, the incorporation of this compound into a polymer backbone yields a polymeric prodrug with potential for use in medical applications such as treatment of gastrointestinal and periodontal diseases. In vivo studies were conducted by implanting polymer matrices into the submucosal gingiva of mice. Histological analysis indicates that salicylic acid reduces inflammation in mucosal tissue when compared with a non-active polyanhydride. Further in vivo studies will be performed along with hematological studies to determine the relative local and systemic concentrations of salicylic acid as a result of polymer degradation. The hydrolysis rate of the ester and anhydride bonds are currently being evaluated in a model compound by high performance liquid chromatography. Prior studies indicated that polymer degradation was more rapid under basic conditions relative to acidic conditions-indicating that anhydride hydrolysis predominates. Upon evaluation of the hydrolysis mechanism for the model compound, in vitro polymer degradation studies will be performed to determine the release rate of salicylic acid. 

2:30 PM GG2.4 
SIZED VESICLE AGGREGATION FOR USE IN NOVEL DRUG DELIVERY SYSTEMS. Edward T. Kisak , Dirk Trommeshauser, Michael T Kennedy, J.A. Zasadzinski, University of California at Santa Barbara, Dept of Chemical Engineering, Santa Barbara, CA. 

We have developed a simple process to rapidly produce vesicle aggregates of a controlled size distribution via a ligand recptor interaction. Streptavidin/avidin was used as the crosslinking agent, attaching to biotin lipids anchored in the vesicle membrane. By controlling the ratio of streptavidin/avidin to biotin, we were able to have a controlled aggregation process. Saturating the available biotins leads to a quenching of aggregation which enables the production of stable sized vesicle aggregates. The process requires no specific mechanical steps to limit or initiate aggregation - aggregation proceeds by simple diffusion and reaction between the proteins and biotins. We followed the size of aggregates formed using dynamic light scattering for different protein to biotin ratios at varying concentrations. We also followed aggregation with fluorescence spectroscopy using BODIPY labeled streptavidin and avidin. Freeze-fracture TEM pictures were taken of various samples to back the light scattering and fluorescence results. A mathematical model was developed that is consistent with the experimental results and shows a transition from massive to size-limited aggregates. The size-limited aggregates will then be used for the production of a complex drug delivery vehicle known as the vesosome, which consists of a vesicle aggregate encapsulated in a second membrane. 

2:45 PM GG2.5 
PHASE INVERSION DYNAMICS OF PLGA SOLUTIONS RELATED TO DRUG DELIVERY. Anthony McHugh , Paul Graham, Kevin Brodbeck, Univ of Illinois, Dept of Chemical Engineering, Urbana, IL. 

Dark ground optical microscopy, electron microscopy, and HPLC (high performance liquid chromotography) have been used to quantify the effects of formulation changes on the phase inversion dynamics and in-vitro/in-vivo drug release properties of a PLGA-based drug delivery system. In-vitro gel growth rate and water influx rates are determined from plots of the square of the respective front motion with time. Results show that additives that accelerate the solution gelation rate at constant morphology result in high initial release rates. Conversely, additives that slow the rate of gelation dramatically reduce the initial drug release rate and lead to a more dense sponge like morphology. Moreover, the phase inversion dynamics and morphology are the same regardless of whether the solutions are quenched with water, a PBS buffer solution or horse serum. 

3:30 PM *GG2.6 
NOVEL pH-SENSITIVE HYDROGELS WITH PEG-TETHERED CHAINS FOR ORAL DELIVERY OF CALCITONIN. Madeline Torres-Lugo , Nicholas A. Peppas, Purdue University, School of Chemical Engineering, West Lafayette, IN. 

The current treatments for osteoporosis, a bone disease in which the bone tissue mass per unit volume is progressively reduced causing skeletal weakness, include estrogen replacement therapy, biophosphates, fluorides, and calcitonin. The main disadvantages of the first three treatments are their side effects. As a therapeutic agent for the treatment of osteoporosis and other bone diseases, calcitonin possesses lesser side effects. Calcitonin, a 32 amino acid polypeptide, is a naturally occurring hormone involved in calcium regulation and bone metabolism. This advantage, however, is accompanied by a major disadvantage, as with all peptides, it cannot be delivered directly through the gastrointestinal track. The main objective of this work was to design an oral drug delivery system for the delivery of salmon calcitonin through the gastrointestinal track. The major challenge in the oral delivery of peptides is to overcome gastric and intestinal degradation. pH sensitive hydrogels are suitable candidates for the oral drug delivery of peptides due to their ability to respond to their environment. We have developed a new type of hydrogel films composed of poly(methacrylic acid) grafted with poly(ethylene glycol) which can be used as drug delivery carriers for salmon calcitonin. These hydrogels were prepared by solution free radical polymerization. They were molecularly designed to contain poly(ethylene glycol) tethered chains promoting mucosal adhesion and providing calcitonin protection, as well as methacrylic acid moieties, which act as calcium binders leading to epithelial cell junction opening. Solutions of 2.6 mg/ml of salmon calcitonin were used to load the protein into the gels at a pH=7 and constant ionic strength of 0.1M. In vitro release studies were performed at pH=7 and 37C, while keeping an ionic strength of 0.1M. Calcitonin release was achieved. The release behavior was analyzed by Fickian diffusion, and calcitonin diffusion coefficients were determined at various pH conditions. 

4:00 PM GG2.7 
THE INFLUENCE OF FUMARIC ACID ON BIOADHESIVE POLYMER COMPOSITIONS. C.A. Santos , B.D. Freedman, S. Ghosn, and E. Mathiowitz, Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI. 

Bioadhesive polymers are useful as drug delivery systems designed to adhere to the gastrointestinal lumen. The interaction between polymer and mucosal tissue influences residence time of the polymeric device and greatly affects the bioavailability of encapsulated drug. Polymers which are more bioadhesive will remain in the GI lumen for a longer duration and may increase drug delivery. Our lab has focused on polyanhydride microspheres for use as oral drug delivery devices. Poly(fumaric-co-sebacic anhydride) [P(FA:SA)] has demonstrated impressive results in a variety of in vitro and in vivo experiments designed to test bioadhesion of microspheres. Among different molar ratios of P(FA:SA), we observed increasing adhesion with increasing FA content. Using a modified microbalance technique, P(FA:SA)10:90 yielded a tensile work measurement of 82.9940.35 nJ while that for P(FA:SA)70:30 was 453.2382.67 nJ. We also used a low molecular weight substance, fumaric anhydride oligomer (FAPP), which increases the bioadhesive properties of P(FA:SA) as well as the relatively non-bioadhesive polymer poly(caprolactone) (PCL). In similar testing, tensile work of P(FA:SA)20:80 was 32.9520.27 nJ, and P(FA:SA)20:80 with 25 FAPP yielded a result of 556.28195.94 nJ. Adhesion testing with PCL yielded a tensile work measurement of 7.936.11 nJ, while that for PCL with 25 FAPP was 1629.54532.69 nJ. The effect of FA on drug delivery was evaluated in vitro using the P(FA:SA) and FAPP blend with the everted intestinal sac technique. We found that a low molecular weight drug encapsulated in P(FA:SA)20:80 passed through the intestinal lumen to the interior of the sac to yield a concentration of 11.173.09 mg/dL, and drug encapsulated in P(FA:SA)20:80 with 10 FAPP yielded 16.255.58 mg/dL. Unencapsulated drug passed through the intestinal lumen to yield a concentration of 8.090.51 mg/dL. Our experiments demonstrate that fumaric acid content is a very important factor in bioadhesion. 

4:15 PM GG2.8 
OF THE PHYSICO-CHEMICAL PROPERTIES OF A NOVEL BARIUM SULPHATE PREPARATION FOR THE X-RAY EXAMINATION OF THE INTESTINE. Barbara Laermann and Paul O'Brien, Imperial College of Science, Technology and Medicine, London, UNITED KINGDOM; Clive Bartram, St. Mark's Hospital, Northwick Park, Watford Harrow, Middlesex, UNITED KINGDOM. 

Novel barium sulphate test preparations with defined rheological properties have been developed providing both low viscosity and high density (containing high concentrations of barium sulphate). The relationship between volume fraction and both high-shear and low-shear viscosity was carried out using steady-state shear stress-shear rate measurements in order to obtain the relative viscosity r, the limited packing fraction _m, and the adsorbed layer thickness. Viscoelasticity was investigated using oscillatory shear measurements. The particles should have an enhanced hydrophilic surface. This property should allow the particles to penetrate through the mucus layer of the gastro-intestinal tract and be enhanced by complete polysaccharide adsorption coverage of the particle surface. Adsorption isotherms of chondroitin sulphate on barium sulphate from aqueous solution have been determined using UV/VIS spectrophotometry. Solid state NMR, FTIR spectroscopy and SEM has been investigated to analyse adsorption behaviour on an molecular level. Neutron Scattering experiments, SANS, and^1H NMR relaxation time studies showed that the adsorbed polymer layer forms an interface with a density gradient between particles and aqueous polymer solution. Coating study of barium sulphate suspension onto intestinal mouse mucosa were carried out. A model for testing the coating thickness and particle packing of proprietary and test suspensions was developed.