Constant Potassium Chloride Release from Microporous Membrane-Coated Tablets Prepared with Aqueous Colloidal Polymer Dispersions

To achieve constant drug release and to avoid the use of organic solvents, potassium chloride tablets were coated with aqueous latexes containing dispersed pore-formers with pH-dependent solubility characteristics. The pore-forming agent, dibasic calcium phosphate, was insoluble in the latex but soluble at low pH. Upon contact with simulated gastric fluids, it leached out rapidly to form a rate-controlling, microporous membrane. The release of potassium chloride was linear with time up to 75–80% drug released. It increased with increasing level of pore-former and decreasing membrane thickness but was independent of the degree of agitation and the pH of the dissolution medium after leaching of the pigments. Upon storage at different relative humidities, moisture uptake of the film coat and variations in the release profiles over time were minimal.     

Mechanical Properties of Dry and Wet Cellulosic and Acrylic Films Prepared from Aqueous Colloidal Polymer Dispersions Used in the Coating of Solid Dosage Forms

The mechanical properties of dry and wet polymeric films prepared from various aqueous polymeric dispersions were evaluated by a puncture test. They were studied with respect to type of polymer dispersion [cellulosic: Aquacoat and Surelease; acrylic: Eudragit NE, L, RS, and RL 30 D], plasticizer type (water-soluble or water-insoluble), drying or curing conditions, method of film preparation (pseudolatex- vs solvent casting) and ratio of Eudragit RS/RL 30 D in mixed Eudragit RS/RL films. Dry and wet mechanical strengths of the polymeric films depended primarily on the types of the colloidal polymer dispersion and the plasticizer. Films prepared from ethylcellulose dispersions resulted in very weak and brittle films when compared to the acrylic films. Pseudolatex-cast ethylcellulose films showed lower puncture strength and elongation values when compared to those of the solvent-cast films. Curing of the pseudolatex-cast ethylcellulose films had minimal effects on their mechanical properties. Eudragit L 30D, an enteric polymer dispersion, resulted in brittle films in the dry state, but in very flexible films in the wet state because of the plasticization effect of water. Wet Eudragit RS 30 D polymer films plasticized with water-insoluble plasticizers were significantly more flexible than the corresponding wet films plasticized with water-soluble plasticizers. The water-soluble plasticizers leached from the films during exposure to the aqueous medium, while the water-insoluble plasticizers were almost completely retained within the wet films. The low permeability of a water-soluble drug, chlorpheniramine maleate, and the weak mechanical properties of Aquacoat films could suggest osmotic driven/rupturing effects as the release mechanisms from Aquacoat-coated dosage forms.     

Development of pulsatile release tablets with swelling and rupturable layers.

A tablet system consisting of cores coated with two layers of swelling and rupturable coatings was prepared and evaluated as pulsatile drug delivery system. Cores containing buflomedil HCl as model drug were prepared by direct compression of different ratios of spray-dried lactose and microcrystalline cellulose and were then coated sequentially with an inner swelling layer containing a superdisintegrant (croscarmellose sodium) and an outer rupturable layer of ethylcellulose. The effect of core composition, level of swelling layer and rupturable coating, and magnesium stearate in rupturable layer was investigated. Mechanical properties of ethylcellulose films in the dry and wet state were characterized with a puncture test. Rupture and dissolution tests were performed using the USP XXIV paddle method at 50 rpm in 0.1 N HCl. The lag time of the pulsatile release tablets decreased with increasing amount of microcrystalline cellulose in the cores and increased with increasing levels of both swelling layer and rupturable ethylcellulose coating. Increasing levels of the ethylcellulose coating retarded the water uptake and thus prolonged the lag time. Addition of magnesium stearate to the ethylcellulose coating lowered the mechanical strength of the film and improved the robustness of the system.     

A Novel Approach to the Oral Delivery of Micro- or Nanoparticles

A novel oral multiple-unit dosage form which overcame many of the problems commonly observed during the compression of microparticles into tablets was developed in this study. Micro- or nano-particles were entrapped in beads formed by ionotropic gelation of the charged polysaccharide, chitosan or sodium alginate, in solutions of the counterion, tripolyphosphate (TPP) or calcium chloride (CaCl₂), respectively. The described technique did not change the physical properties of the microparticles, and it allowed a high microparticle loading (up to 98%). The ionic character of the polymers allowed pH-dependent release of the microparticles. Chitosan beads disintegrated and released the microparticles in 0.1 N HC1, while calcium alginate beads stayed intact in 0.1 N HC1 but rapidly disintegrated in simulated intestinal fluids. Coating the calcium alginate beads with cellulose acetate phthalate resulted in an enteric drug delivery system. Scanning electron microscopy and dissolution and disintegration tests were used to characterize the microparticle-containing beads. The disintegration time of the beads was studied as a function of the solution viscosity of the polysaccharide, gelation time, counterion concentration, and method of drying.     

Evaluation of Drug-Containing Polymer Films Prepared from Aqueous Latexes

Polymeric films containing salicylic acid or propranolol HC1 were prepared by casting and drying a drug-containing, aqueous colloidal polymer dispersion (Eudragit NE 30D) as an alternative to films cast from organic polymer solutions. The drug was either dissolved (salicylic acid) or dissolved/ dispersed (propranolol HC1) in the polymeric matrix. Incompatibilities (flocculation or coagulation) between salts of basic drugs and two ethylcellulose latexes were overcome by substituting the anionic surfactants with a nonionic surfactant (Pluronic P103). The drug release was studied as a function of drug loading, film thickness, amount of hydrophilic additive (hydroxypropyl methylcellulose), and storage humidity. The release of propranolol HC1 (monolithic dispersion) was a combination of diffusion through the polymer and pores or channels; the extent of each release mechanism depended on the drug loading. On DSC thermograms, melting transitions were obtained with monolithic dispersions but not with monolithic solutions. The heat of fusion was linearly correlated to the amount of drug in the films. The amount of drug remaining in the film after the dissolution study was not detectable and corresponded to the drug dissolved in the polymer. The drug release increased with increased drug loading and increased amount of hydroxypropyl methylcellulose but was independent of film thickness and relatively insensitive to different storage humidities.