Browsing by Subject "Eudragit"
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Item Implications of plasticization on the properties of hot-melt extruded oral dosage forms(2009-12) Schilling, Sandra Ursula; McGinity, James W.The influence of plasticization and other formulation factors on the properties of hot-melt extruded dosage forms for the controlled release of water-soluble active compounds was investigated. Citric acid monohydrate was demonstrated to function as a solid-state plasticizer in hot-melt extruded Eudragit® RS PO tablets and in cast films when concentrations below the compatibility limit were employed. Melting of the organic acid and solubilization in the polymer during extrusion were necessary to observe the plasticizing effect. The release rate of diltiazem hydrochloride, used as a high-melting, water-soluble model drug, from melt extruded Eudragit® RS PO matrix tablets increased and became independent of the original drug particle size in the presence of citric acid monohydrate. Thermal analysis of physical mixtures demonstrated that citric acid promoted drug melting during extrusion by interaction and melting point depression. Diltiazem hydrochloride remained amorphous in the final dosage form, and leaching of citric acid monohydrate enhanced drug diffusion by increasing the matrix porosity. Delayed-release matrix pellets with particle sizes below one mm were prepared by hot-melt extrusion, and the influence of the matrix forming polymer and the type and level of plasticizer on the processibility and release properties was investigated. Pellets complied with the USP requirement for delayed release articles to release less than 10% drug at pH 1.2 after 2 hours when plasticized Eudragit® S100 was used as the release-controlling material. High levels of efficient plasticizers had to be employed to decrease the polymeric melt viscosity, increase the process yield and enable extrusion at moderate temperatures to avoid instabilities during processing and storage. The aqueous solubility of the plasticizer further impacted the drug release rate in acid. A novel application of hot-melt extrusion for the preparation of monolithic matrices comprising enteric coated particles was studied. The influence of the mechanical strength of the multiparticulates, pellet loading and nature of the hydrophilic carrier material on the preservation of the delayed-release properties after extrusion was investigated. Soft particles coated with brittle films remained intact when low-melting carriers that did not solubilize the enteric film during extrusion were used, and the dissolution profile was stable over one year.Item Mucoadhesive films for the buccal delivery of insulin(2012-12) Morales, Javier Octavio; Williams, Robert O., 1956-; McConville, Jason Thomas; Smyth, Hugh D; Cui, Zhengrong; Roy, KrishnenduTo address the need of a patient friendly and therapeutically effective method of administration of insulin (Ins) we sought to develop mucoadhesive films for delivery through the buccal mucosa. Ins is a labile molecule exhibiting limited activity and stability in solid solutions in films and other solid delivery devices. Early investigations outlined in Chapter 3 revealed the need for a certain particle size (below the one micrometer) for the addition of particulate material in films. In Chapter 4 a novel method for the manufacture of protein-coated nanoparticles (PCNP) is depicted. Successful particle batches were achieved in terms of size, uniformity, stability and activity and these particles were further investigated for their inclusion on films for buccal delivery. The method of manufacture of particles was based on an antisolvent co-precipitation process that immobilized macromolecules to the surface of crystalline core particles resulting in high yields and highly active protein loaded particles. Films loaded with PCNP were developed and characterized in Chapter 5. Lysozyme was utilized as a model macromolecule and high yields and activity were obtained after manufacture, demonstrating that after all the processing the protein is subjected to, activity is preserved. Using Eudragit® RLPO (ERL) as the matrix forming polymer, films with excellent mucoadhesion were developed. Here is described a high mucoadhesion for ERL that was even further increased by the addition of the water soluble PCNP. This occurred by the water movement into the ERL matrix that the solubilizing particles generate. Finally, films containing Ins were developed and assayed for permeation through buccal mucosa. By adapting the method of manufacture, Ins-coated nanoparticles were obtained and embedded in films. ERL films corroborated previous findings by exhibiting excellent performance. Investigations on the permeation of Ins through buccal mucosa revealed that the inclusion of Ins in films enhanced its permeation in comparison with a control Ins solution. Thus here is described the successful development of mucoadhesive films for the buccal delivery of Ins.