ABSTRACT
Hot-melt extruded tablets were prepared using Eudragit S 100 as the polymeric carrier to target delivery of 5-aminosalicylic acid (5-ASA) to the colon. Scanning electron microscopy, modulated differential scanning calorimetry and X-ray diffraction analysis of the hot-melt tablet extrudates demonstrated that 5-ASA remained crystalline and was homogeneously dispersed throughout the polymer matrix. A pre-plasticization step was necessary when incorporating triethyl citrate (TEC) into the formulation in order to achieve uniform mixing of the polymer and plasticizer, effectively reduce the polymer glass transition temperature (T(g)), and to lower the processing temperatures. The concentration of TEC in the extrudates not only influenced the processing temperature, but also influenced the drug release rates from the extruded tablets due to leaching of the TEC during dissolution testing. Citric acid monohydrate was found to plasticize Eudragit S 100, and when combined with TEC in the powder blend, the temperatures required for processing were reduced. Tablets containing citric acid released drug at a slower rate as a result of the suppression of polymer ionization due to a decrease in the micro-environmental pH of the tablet. The drug release profiles of the extruded tablets were found to fit both diffusion and surface erosion models.
Subject(s)
Colon , Drug Delivery Systems/methods , Mesalamine/chemistry , Mesalamine/pharmacokinetics , Chemistry, Pharmaceutical , Colon/drug effects , Colon/metabolism , Mesalamine/administration & dosage , TabletsABSTRACT
The influences of aqueous polymeric subcoats and pellet composition on the release properties of a highly water-soluble drug, chlorpheniramine maleate (CPM), from enteric coated pellets were investigated. Three different aqueous polymeric subcoats, Eudragit RD 100, Eudragit RS 30D, and Opadry AMB, were applied to 10% w/w CPM-loaded pellets that were then enteric coated with Eudragit L 30D-55. Observed drug release from the coated pellets in acidic media correlated with water vapor transmission rates derived for the subcoat films. The influence of pellet composition on retarding the release of CPM from enteric coated pellets in 0.1 N HCl was investigated. The rate of drug release was greatest for pellets prepared with lactose, microcrystalline cellulose, or dibasic calcium phosphate compared with pellets formulated with citric acid and microcrystalline cellulose. Citric acid reduced the pellet micro-environmental pH, decreasing the amount of drug leakage in 0.1 N HCL during the first 2 hr of dissolution. Polymer flocculation was observed when CPM was added to the Eudragit L 30D-55 dispersion. An adsorption isotherm was generated for mixtures of CPM and the polymer and the data were found to fit the Freundlich model for adsorption. Adsorption of CPM to the polymer decreased with the addition of citric acid to the drug-polymer mixtures.
Subject(s)
Chlorpheniramine/chemistry , Histamine H1 Antagonists/chemistry , Acrylic Resins/chemistry , Adsorption , Chlorpheniramine/administration & dosage , Fourier Analysis , Histamine H1 Antagonists/administration & dosage , Hydrogen-Ion Concentration , Methacrylates/chemistry , Plasticizers , Polymers/chemistry , Polyvinyl Alcohol/chemistry , Porosity , Solubility , Tablets, Enteric-Coated/chemistry , Technology, Pharmaceutical , X-Ray DiffractionABSTRACT
The influence of subcoat application and micro-environmental pH on the dissolution properties of enteric coated sodium valproate pellets was investigated. The pellets were prepared by solution-layering or wet-mass extrusion-spheronization methods. In order to pass the USP enteric test, the solution-layered and wet-mass extruded pellets required 35 and 25% weight gain of Eudragit L 30D-55, respectively. The application of a subcoat of either Methocel-E5 (HPMC) or Opadry AMB to the pellets resulted in a delay in sodium valproate release in 0.1N HCl. Further delay in drug release was observed when citric acid was present in a HPMC subcoat or when added to the core pellet formulation. The amount of drug released from coated pellets was a function of the level of citric acid in the pellet core or subcoat and subsequent micro-environmental pH of the pellets. Citric acid exerted a plasticizing effect on the enteric polymer film and improved film formation and polymer coalescence. When greater than 10% (w/w) citric acid was present in the pellets, a decrease in drug content was observed due to the conversion of sodium valproate to the volatile compound, valproic acid. Pellets containing less than 10% (w/w) citric acid maintained potency during processing.
